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Sample records for double negative cd4-cd8

  1. File list: Unc.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 Unclassified Blood CD4 CD8 double negative... cells SRX199974,SRX398232 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  2. File list: DNS.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 DNase-seq Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  3. File list: Pol.Bld.05.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.05.AllAg.CD4_CD8_double_negative_cells mm9 RNA polymerase Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.05.AllAg.CD4_CD8_double_negative_cells.bed ...

  4. File list: ALL.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 All antigens Blood CD4 CD8 double negative...091663,SRX091665 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  5. File list: InP.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 Input control Blood CD4 CD8 double negative...,SRX091680 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  6. File list: NoD.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 No description Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  7. File list: Pol.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 RNA polymerase Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  8. File list: NoD.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 No description Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  9. File list: NoD.Bld.05.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Bld.05.AllAg.CD4_CD8_double_negative_cells mm9 No description Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Bld.05.AllAg.CD4_CD8_double_negative_cells.bed ...

  10. File list: ALL.Bld.10.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.10.AllAg.CD4_CD8_double_negative_cells mm9 All antigens Blood CD4 CD8 double negative...692952,SRX692966 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.10.AllAg.CD4_CD8_double_negative_cells.bed ...

  11. File list: ALL.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 All antigens Blood CD4 CD8 double negative...091667,SRX091665 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  12. File list: Unc.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 Unclassified Blood CD4 CD8 double negative... cells SRX398232,SRX199974 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  13. File list: InP.Bld.05.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.CD4_CD8_double_negative_cells mm9 Input control Blood CD4 CD8 double negative...,SRX091680 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.CD4_CD8_double_negative_cells.bed ...

  14. File list: DNS.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 DNase-seq Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  15. File list: Unc.Bld.05.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.CD4_CD8_double_negative_cells mm9 Unclassified Blood CD4 CD8 double negative... cells SRX398232,SRX199974 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.CD4_CD8_double_negative_cells.bed ...

  16. File list: ALL.Bld.05.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.CD4_CD8_double_negative_cells mm9 All antigens Blood CD4 CD8 double negative...692954,SRX692966 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.CD4_CD8_double_negative_cells.bed ...

  17. File list: Pol.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 RNA polymerase Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  18. File list: DNS.Bld.10.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.10.AllAg.CD4_CD8_double_negative_cells mm9 DNase-seq Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.10.AllAg.CD4_CD8_double_negative_cells.bed ...

  19. File list: Unc.Bld.10.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.10.AllAg.CD4_CD8_double_negative_cells mm9 Unclassified Blood CD4 CD8 double negative... cells SRX398232,SRX199974 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.10.AllAg.CD4_CD8_double_negative_cells.bed ...

  20. File list: DNS.Bld.05.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.05.AllAg.CD4_CD8_double_negative_cells mm9 DNase-seq Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.05.AllAg.CD4_CD8_double_negative_cells.bed ...

  1. File list: Pol.Bld.10.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.10.AllAg.CD4_CD8_double_negative_cells mm9 RNA polymerase Blood CD4 CD8 double negative... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.10.AllAg.CD4_CD8_double_negative_cells.bed ...

  2. File list: InP.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 Input control Blood CD4 CD8 double negative...,SRX091680 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  3. File list: InP.Bld.10.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.10.AllAg.CD4_CD8_double_negative_cells mm9 Input control Blood CD4 CD8 double negative...,SRX091680 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.10.AllAg.CD4_CD8_double_negative_cells.bed ...

  4. File list: Oth.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 TFs and others Blood CD4 CD8 double negative...3,SRX692973,SRX1205897,SRX018101,SRX692982 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  5. File list: His.Bld.50.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.CD4_CD8_double_negative_cells mm9 Histone Blood CD4 CD8 double negative...92952,SRX692966,SRX091663,SRX091664,SRX091667,SRX091665 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.CD4_CD8_double_negative_cells.bed ...

  6. File list: Oth.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 TFs and others Blood CD4 CD8 double negative...97,SRX692982,SRX091677,SRX091674,SRX018101 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  7. File list: Oth.Bld.05.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.AllAg.CD4_CD8_double_negative_cells mm9 TFs and others Blood CD4 CD8 double negative...2,SRX692974,SRX018101,SRX1205897,SRX091677 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.AllAg.CD4_CD8_double_negative_cells.bed ...

  8. File list: His.Bld.20.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.20.AllAg.CD4_CD8_double_negative_cells mm9 Histone Blood CD4 CD8 double negative...92966,SRX692952,SRX091667,SRX692965,SRX091663,SRX091665 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.20.AllAg.CD4_CD8_double_negative_cells.bed ...

  9. File list: Oth.Bld.10.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.AllAg.CD4_CD8_double_negative_cells mm9 TFs and others Blood CD4 CD8 double negative...6,SRX692974,SRX1205897,SRX091677,SRX018101 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.AllAg.CD4_CD8_double_negative_cells.bed ...

  10. File list: His.Bld.10.AllAg.CD4_CD8_double_negative_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.10.AllAg.CD4_CD8_double_negative_cells mm9 Histone Blood CD4 CD8 double negative...92964,SRX692965,SRX692954,SRX692950,SRX692952,SRX692966 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.CD4_CD8_double_negative_cells.bed ...

  11. CD4/CD8 double negative mycosis fungoides with PD-1 (CD279) expression--a disease of follicular helper T-cells?

    OpenAIRE

    Kempf, Werner; Dmitry V. Kazakov; Cipolat, Claudio; Kutzner, Heinz; Roncador, Giovanna; Tomasini, Dario

    2012-01-01

    CD4/CD8 double negative mycosis fungoides (MF) is a rare phenotypic variant of this epidermotropic cutaneous T-cell lymphoma. Clinically, this MF form manifests with unusual appearances such as annular lesions confined to one body region as in our patient in whom the lesions were found on the left lower leg. The cellular origin of CD4/CD8 double negative MF is unknown. In our case, the intraepidermal CD4/CD8 double negative clonal T-lymphocytes (CD2+, CD4-, CD8-, CD30-, beta-F1+) expressed pr...

  12. CD4/CD8 double negative mycosis fungoides with PD-1 (CD279) expression--a disease of follicular helper T-cells?

    Science.gov (United States)

    Kempf, Werner; Kazakov, Dmitry V; Cipolat, Claudio; Kutzner, Heinz; Roncador, Giovanna; Tomasini, Dario

    2012-10-01

    CD4/CD8 double negative mycosis fungoides (MF) is a rare phenotypic variant of this epidermotropic cutaneous T-cell lymphoma. Clinically, this MF form manifests with unusual appearances such as annular lesions confined to one body region as in our patient in whom the lesions were found on the left lower leg. The cellular origin of CD4/CD8 double negative MF is unknown. In our case, the intraepidermal CD4/CD8 double negative clonal T-lymphocytes (CD2+, CD4-, CD8-, CD30-, beta-F1+) expressed programmed death-1 but were negative for CXCL-13 and cytotoxic molecules (TIA-1, granzyme B, perforin). Our observation may give an insight into the histogenesis of this unique MF variant and may also be of therapeutic significance because programmed death-1 may serve as a target for therapeutic intervention.

  13. The role of intrahepatic CD3+/CD4-/CD8- double negative T (DN T) cells in enhanced acetaminophen toxicity.

    Science.gov (United States)

    Getachew, Yonas; Cusimano, Frank A; James, Laura P; Thiele, Dwain L

    2014-10-15

    The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB -/-) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB -/-) mice. Analysis revealed that GrB -/- mice had an increased population of intrahepatic CD3 (+), CD4 (-), and CD8 (-) lymphocytes expressing the CD69 activation marker and Fas ligand. Depletion of these cells in the GrB -/- and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB -/- IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (-), CD8 (-), NK1.1 (-) T cells. Depletion of these cells from GrB -/- mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery. Published by Elsevier Inc.

  14. CD4+/CD8+ double-positive T cells

    DEFF Research Database (Denmark)

    Overgaard, Nana H; Jung, Ji-Won; Steptoe, Raymond J

    2015-01-01

    CD4(+)/CD8(+) DP thymocytes are a well-described T cell developmental stage within the thymus. However, once differentiated, the CD4(+) lineage or the CD8(+) lineage is generally considered to be fixed. Nevertheless, mature CD4(+)/CD8(+) DP T cells have been described in the blood and peripheral...... cells, CD4(+)/CD8(+) T cell populations, outside of the thymus, have recently been described to express concurrently ThPOK and Runx3. Considerable heterogeneity exists within the CD4(+)/CD8(+) DP T cell pool, and the function of CD4(+)/CD8(+) T cell populations remains controversial, with conflicting...... reports describing cytotoxic or suppressive roles for these cells. In this review, we describe how transcriptional regulation, lineage of origin, heterogeneity of CD4 and CD8 expression, age, species, and specific disease settings influence the functionality of this rarely studied T cell population....

  15. Specific activation of CD4(-) CD8(-) double-negative T cells by Trypanosoma cruzi-derived glycolipids induces a proinflammatory profile associated with cardiomyopathy in Chagas patients.

    Science.gov (United States)

    Passos, L S A; Magalhães, L M D; Soares, R P; Marques, A F; Nunes, M do C P; Gollob, K J; Dutra, W O

    2017-10-01

    Cardiomyopathy is the most severe outcome of Chagas disease, causing more than 12 000 deaths/year. Immune cells participate in cardiomyopathy development either by direct tissue destruction, or by driving inflammation. We have shown that CD4(-) CD8(-) [double-negative (DN)] T cells are major sources of inflammatory and anti-inflammatory cytokines, associated with the cardiac (CARD) and indeterminate (IND) forms of Chagas disease, respectively. Here, we sought to identify Trypanosoma cruzi-derived components that lead to activation of DN T cells in Chagas patients. Glycolipid (GCL), lipid (LIP) and protein-enriched (PRO) fractions derived from trypomastigote forms of T. cruzi were utilized to stimulate cells from IND and CARD patients to determine DN T cell activation by evaluating CD69 and cytokine expression. We observed that GCL, but not LIP or PRO fractions, induced higher activation of DN T cells, especially T cell receptor (TCR)-γδ DN T, from IND and CARD. GCL led to an increase in tumour necrosis factor (TNF) and interleukin (IL)-10 expression by TCR-γδ DN T cells from IND, while inducing IFN-γ expression by TCR-γδ DN T cells from CARD. This led to an increase in the ratio IFN-γ/IL-10 in TCR-γδ DN T cells from CARD, favouring an inflammatory profile. These results identify GCL as the major T. cruzi component responsible for activation of DN T cells in chronic Chagas disease, associated predominantly with an inflammatory profile in CARD, but not IND. These findings may have implications for designing new strategies of control or prevention of Chagas disease cardiomyopathy by modulating the response to GCL. © 2017 British Society for Immunology.

  16. FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function.

    Science.gov (United States)

    Magerus-Chatinet, Aude; Stolzenberg, Marie-Claude; Loffredo, Maria S; Neven, Bénédicte; Schaffner, Catherine; Ducrot, Nicolas; Arkwright, Peter D; Bader-Meunier, Brigitte; Barbot, José; Blanche, Stéphane; Casanova, Jean-Laurent; Debré, Marianne; Ferster, Alina; Fieschi, Claire; Florkin, Benoit; Galambrun, Claire; Hermine, Olivier; Lambotte, Olivier; Solary, Eric; Thomas, Caroline; Le Deist, Francoise; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2009-03-26

    Autoimmune lymphoproliferative syndrome (ALPS) is characterized by splenomegaly, lymphadenopathy, hypergammaglobulinemia, accumulation of double-negative TCRalphabeta(+) CD4(-)CD8(-) T cells (DNT cells), and autoimmunity. Previously, DNT cell detection and a functional defect of T cells in a FAS-induced apoptosis test in vitro had been used for ALPS diagnosis. However, a functional defect can also be detected in mutation-positive relatives (MPRs) who remain free of any ALPS-related disease. In contrast, lymphocytes from patients carrying a somatic mutation of FAS exhibit normal sensitivity to FAS-induced apoptosis in vitro. We assessed the soluble FAS-L concentration in the plasma of ALPS patients carrying FAS mutations. Overall, we showed that determination of the FAS-L represents, together with the IL-10 concentration and the DNT cell percentage, a reliable tool for the diagnosis of ALPS.

  17. Peripheral canine CD4(+)CD8(+) double-positive T cells - unique amongst others.

    Science.gov (United States)

    von Buttlar, Heiner; Bismarck, Doris; Alber, Gottfried

    2015-12-15

    T lymphocytes co-expressing CD4 and CD8 ("double-positive T cells") are commonly associated with a thymic developmental stage of T cells. Their first description in humans and pigs as extrathymic T cells with a memory phenotype almost 30 years ago came as a surprise. Meanwhile peripheral double-positive T cells have been described in a growing number of different species. In this review we highlight novel data from our very recent studies on canine peripheral double-positive T cells which point to unique features of double-positive T cells in the dog. In contrast to porcine CD4(+)CD8(+) T cells forming a homogenous cellular population based on their expression of CD4 and CD8α, canine CD4(+)CD8(+) T cells can be divided into three different cellular subsets with distinct expression levels of CD4 and CD8α. Double-positive T cells expressing CD8β are present in humans and dogs but absent in swine. Moreover, canine CD4(+)CD8(+) T cells can not only develop from CD4(+) single-positive T cells but also from CD8(+) single-positive T cells. Together, this places canine CD4(+)CD8(+) T cells closer to their human than porcine counterparts since human double-positive T cells also appear to be heterogeneous in their CD4 and CD8α expression and have both CD4(+) and CD8(+) T cells as progenitor cells. However, CD4(+) single-positive T cells are the more potent progenitors for canine double-positive T cells, whereas CD8(+) single-positive T cells are more potent progenitors for human double-positive T cells. Canine double-positive T cells have an activated phenotype and may have as yet unrecognized roles in vivo in immunity to infection or in inflammatory diseases such as chronic infection, autoimmunity, allergy, or cancer.

  18. File list: DNS.Bld.20.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.20.AllAg.CD4_CD8_double_positive_cells mm9 DNase-seq Blood CD4 CD8 double positive... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.20.AllAg.CD4_CD8_double_positive_cells.bed ...

  19. File list: ALL.Bld.50.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.50.AllAg.CD4_CD8_double_positive_cells mm9 All antigens Blood CD4 CD8 double positive...X018116,SRX018113 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.CD4_CD8_double_positive_cells.bed ...

  20. File list: Unc.Bld.05.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.05.AllAg.CD4_CD8_double_positive_cells mm9 Unclassified Blood CD4 CD8 double positive... cells SRX199993 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.05.AllAg.CD4_CD8_double_positive_cells.bed ...

  1. File list: DNS.Bld.50.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Bld.50.AllAg.CD4_CD8_double_positive_cells mm9 DNase-seq Blood CD4 CD8 double positive... cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Bld.50.AllAg.CD4_CD8_double_positive_cells.bed ...

  2. File list: His.Bld.50.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.50.AllAg.CD4_CD8_double_positive_cells mm9 Histone Blood CD4 CD8 double positive...iencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.CD4_CD8_double_positive_cells.bed ...

  3. File list: Pol.Bld.20.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Bld.20.AllAg.CD4_CD8_double_positive_cells mm9 RNA polymerase Blood CD4 CD8 double positive... cells SRX063926,SRX099398,SRX099388 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Bld.20.AllAg.CD4_CD8_double_positive_cells.bed ...

  4. File list: His.Bld.05.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.CD4_CD8_double_positive_cells mm9 Histone Blood CD4 CD8 double positive...iencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.CD4_CD8_double_positive_cells.bed ...

  5. File list: Unc.Bld.50.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Bld.50.AllAg.CD4_CD8_double_positive_cells mm9 Unclassified Blood CD4 CD8 double positive... cells SRX199993 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Bld.50.AllAg.CD4_CD8_double_positive_cells.bed ...

  6. File list: Unc.Bld.20.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  1. File list: Oth.Bld.20.AllAg.CD4_CD8_double_positive_cells [Chip-atlas[Archive

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  8. Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Yongkang Wu

    2014-01-01

    Full Text Available Background & objectives: The presence of CD4+CD8+ (double positive T cells (DPT in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE. Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA, anti-double strain deoxyribonucleic acid (anti-dsDNA, anti-U1 ribonucleoprotein (anti-U1 RNP, anti-sjogren syndrome A (anti-SSA, anti-ribosomal P protein (anti-rib-P, anti-Smith (anti-Sm, anti-Sjogren syndrome B (anti-SSB, complement 3 (C3 and complement 4 (C4. Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001. SLE patients were divided into a ≥1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032. The DPT medians of positive subgroups with anti-dsDNA (P<0.001, anti-U1RNP (P=0.018, anti-SSA (P=0.021 or anti-rib-P (P=0.039 were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006. Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work.

  9. Analysis of CD4+CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions

    Science.gov (United States)

    Waschbisch, A; Sammet, L; Schröder, S; Lee, D-H; Barrantes-Freer, A; Stadelmann, C; Linker, R A

    2014-01-01

    T cells with a CD4+ CD8+ double-positive (DP) phenotype are present in small numbers in the peripheral blood of healthy humans and may have anti-viral capacities. Here we investigate numbers and function of DP T cells in patients with relapsing–remitting multiple sclerosis (MS), either treatment-naive or under therapy with natalizumab. Flow cytometry analysis revealed that frequencies of circulating DP T cells in treatment-naive and natalizumab-treated MS patients are comparable to healthy controls. These cells have a memory phenotype with cytotoxic potential, express high levels of CD49d and are similarly functional in treatment-naive as well as natalizumab-treated MS patients. DP T cells were enriched in the cerebrospinal fluid, but do not invade acutely inflamed MS lesions. In conclusion, DP T cells are functional in MS and may play a role in the immune surveillance of the central nervous system, but do not display functional impairment under natalizumab therapy. PMID:24730443

  10. Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease.

    Directory of Open Access Journals (Sweden)

    Alexandre Morrot

    2011-08-01

    Full Text Available Extrathymic CD4+CD8+ double-positive (DP T cells are increased in some pathophysiological conditions, including infectious diseases. In the murine model of Chagas disease, it has been shown that the protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironment and the lymphoid compartment. In the acute phase, this results in a severe atrophy of the organ and early release of DP cells into the periphery. To date, the effect of the changes promoted by the parasite infection on thymic central tolerance has remained elusive. Herein we show that the intrathymic key elements that are necessary to promote the negative selection of thymocytes undergoing maturation during the thymopoiesis remains functional during the acute chagasic thymic atrophy. Intrathymic expression of the autoimmune regulator factor (Aire and tissue-restricted antigen (TRA genes is normal. In addition, the expression of the proapoptotic Bim protein in thymocytes was not changed, revealing that the parasite infection-induced thymus atrophy has no effect on these marker genes necessary to promote clonal deletion of T cells. In a chicken egg ovalbumin (OVA-specific T-cell receptor (TCR transgenic system, the administration of OVA peptide into infected mice with thymic atrophy promoted OVA-specific thymocyte apoptosis, further indicating normal negative selection process during the infection. Yet, although the intrathymic checkpoints necessary for thymic negative selection are present in the acute phase of Chagas disease, we found that the DP cells released into the periphery acquire an activated phenotype similar to what is described for activated effector or memory single-positive T cells. Most interestingly, we also demonstrate that increased percentages of peripheral blood subset of DP cells exhibiting an activated HLA-DR+ phenotype are associated with severe cardiac forms of human chronic Chagas disease. These cells may

  11. Direct BMP2/4 signaling through BMP receptor IA regulates fetal thymocyte progenitor homeostasis and differentiation to CD4+CD8+ double-positive cell.

    Science.gov (United States)

    Hager-Theodorides, Ariadne L; Ross, Susan E; Sahni, Hemant; Mishina, Yuji; Furmanski, Anna L; Crompton, Tessa

    2014-01-01

    BMP2/4 signaling is required for embryogenesis and involved in thymus morphogenesis and T-lineage differentiation. In vitro experiments have shown that treatment of thymus explants with exogenous BMP4 negatively regulated differentiation of early thymocyte progenitors and the transition from CD4-CD8- (DN) to CD4+CD8+ (DP). Here we show that in vivo BMP2/4 signaling is required for fetal thymocyte progenitor homeostasis and expansion, but negatively regulates differentiation from DN to DP cell. Unexpectedly, conditional deletion of BMPRIA from fetal thymocytes (using the Cre-loxP system and directing excision to hematopoietic lineage cells with the Vav promoter) demonstrated that physiological levels of BMP2/4 signaling directly to thymocytes through BMPRIA are required for normal differentiation and expansion of early fetal DN thymocytes. In contrast, the arrest in early thymocyte progenitor differentiation caused by exogenous BMP4 treatment of thymus explants is induced in part by direct signaling to thymocytes through BMPRIA, and in part by indirect signaling through non-hematopoietic cells. Analysis of the transition from fetal DN to DP cell, both by ex vivo analysis of conditional BMPRIA-deficient thymocytes and by treatment of thymus explants with the BMP4-inhibitor Noggin demonstrated that BMP2/4 signaling is a negative regulator at this stage. We showed that at this stage of fetal T-cell development BMP2/4 signals directly to thymocytes through BMPRIA.

  12. CMV+ Serostatus Associates Negatively with CD4:CD8 Ratio Normalization in Controlled HIV-Infected Patients on cART

    Science.gov (United States)

    Poizot-Martin, Isabelle; Allavena, Clotilde; Duvivier, Claudine; Cano, Carla Eliana; Guillouet de Salvador, Francine; Rey, David; Dellamonica, Pierre; Cuzin, Lise; Cheret, Antoine; Hoen, Bruno

    2016-01-01

    Cytomegalovirus (CMV) infection is common among HIV-infected patients but its repercussion on the course of CD4+ and CD8+ T cells after cART initiation remains elusive. The French Dat'AIDS cohort enrolled 5,688 patients on first-line cART, from which we selected patients who achieved HIV suppression for at least 12 months without modification of cART, and for whom CMV serostatus was available. Five hundred and three patients fulfilled the selection criteria (74% male, median age 43 yrs, 15.5% CDC stage C), of whom 444 (88.3%) were seropositive for CMV (CMV+). Multivariate analyses using mixed-linear models adjusted for the time from HIV suppression, sex, age, transmission risk group, duration of HIV follow-up, the interaction between time from HIV suppression and CMV+ serology, and the nadir CD4 count revealed a negative correlation between CMV+ and CD4:CD8 ratio (coeff. = -0.16; p = 0.001). This correlation was also observed among patients displaying optimal CD4 recovery (≥500 cells/mm3 at M12; coeff. = -0.24; p = 0.002). Hence, CMV+ serostatus antagonizes normalization of the CD4:CD8 ratio, although further analyses of the impact of co-morbidities that associate with CMV serostatus, like HCV infection, are needed to elucidate this antagonism formally. However, this might reflect a premature T cell senescence, thus advocating for a close monitoring of T cells in CMV co-infected patients. In addition, our results raise the question of the benefit of treatment for asymptomatic CMV co-infection in HIV-infected patients. PMID:27824907

  13. Isolation of human CD4/CD8 double-positive, graft-versus-host disease-protective, minor histocompatibility antigen-specific regulatory T cells and of a novel HLA-DR7-restricted HY-specific CD4 clone.

    Science.gov (United States)

    Eljaafari, Assia; Yuruker, Ozel; Ferrand, Christophe; Farre, Annie; Addey, Caroline; Tartelin, Marie-Laure; Thomas, Xavier; Tiberghien, Pierre; Simpson, Elizabeth; Rigal, Dominique; Scott, Diane

    2013-01-01

    Minor histocompatibility (H) Ags are classically described as self-peptides derived from intracellular proteins that are expressed at the cell surface by MHC class I and class II molecules and that induce T cell alloresponses. We have isolated three different T cell populations from a skin biopsy of a patient suffering from acute graft-versus-host disease following sex-mismatched HLA-identical bone marrow transplantation. The first population was: 1) CD4(+)/CD8(+) double-positive; 2) specific for an HLA class I-restricted autosomal Ag; 3) expressed a Tr1 profile with high levels of IL-10, but low IL-2 and IFN-γ; and 4) exerted regulatory function in the presence of recipient APCs. The second was CD8 positive, specific for an HLA class I-restricted autosomally encoded minor H Ag, but was only weakly cytotoxic. The third was CD4 single positive, specific for an HLA-DR7-restricted HY epitope and exerted both proliferative and cytotoxic functions. Identification of the peptide recognized by these latter cells revealed a new human HY epitope, TGKIINFIKFDTGNL, encoded by RPS4Y and restricted by HLA-DR7. In this paper, we show human CD4/CD8 double-positive, acute graft-versus-host disease-protective, minor H Ag-specific regulatory T cells and identify a novel HLA-DR7/ HY T cell epitope, encoded by RPS4Y, a potential new therapeutic target.

  14. Thymic Nurse Cells Support CD4-CD8+ Thymocytes to Differentiate into CD4+CD8+ Cells

    Institute of Scientific and Technical Information of China (English)

    Aidong Li; Xueli Liu; Baochun Duan; Jie Ma

    2005-01-01

    Thymic nurse cells (TNCs) represent a unique microenvironment in the thymus for T cell maturation. In order to investigate the role of thymic nurse cells during T cell differentiation, a TNC clone, RWTE-1, which formed a typical complex with fetal thymocytes in vitro was established from normal Wistar rat. Hanging drop culture method was applied to reveal the interaction between TNCs and thymocytes. Our result revealed that eighty percent of immature CD4-CD8+ cells differentiated into CD4+CD8+ cells after a 12-hour hanging drop culture with RWTE-1. However, in a 12-hour culture of immature CD4-CD8+ cells with or without RWTE-1 supernatant, only 30% of the cells differentiated into CD4+CD8+ cells spontaneously. This observation led to the conclusion that RWTE-1 cell has the capacity to facilitate immature CD4-CD8+ thymocytes to differentiate into CD4+CD8+ T cells by direct interaction.

  15. Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially natural killer T cells, double-positive CD4+ CD8+ cells and B220+ T cells, in mice

    Science.gov (United States)

    Ishimoto, Yuiko; Tomiyama-Miyaji, Chikako; Watanabe, Hisami; Yokoyama, Hisashi; Ebe, Kazuto; Tsubata, Shunsuke; Aoyagi, Yutaka; Abo, TORU

    2004-01-01

    The age-dependent variation in the proportion and number of lymphocyte subsets was examined at various extrathymic sites, including the liver, small intestine, colon and appendix in mice. In comparison with young mice (4 weeks of age), the number of total lymphocytes yielded by all tested organs was greater in adult (9 weeks) and old (40 weeks) mice. The major lymphocyte subset that expanded with age was interleukin-2 receptor (IL-2R) β+ CD3int cells (50% of them expressed NK1.1) in the liver, whereas it was CD3+ IL-2Rβ− NK1.1− cells at all intraepithelial sites in the intestine. Although NK1.1+ CD3+ cells were present at intraepithelial sites in the intestine, the proportion of this subset was rather low. The ratio of CD4 to CD8 tended to decrease among natural killer T (NKT) cells and T cells at all intraepithelial sites in the intestine with age. A unique population of double-positive CD4+ CD8+ cells in the small intestine increased in old mice. B220+ T cells were found mainly in the appendix and colon, and the proportion of these T cells decreased in old mice. Conventional NKT cells were very few in Jα281−/− and CD1d−/− mice in the liver, while NKT cells which existed in the appendix remained unchanged even in these mice. This was because unconventional CD8+ NKT cells were present in the intestine. The present results suggest that despite the fact that both the liver and intraepithelial sites in the intestine carry many extrathymic T cells, the distribution of lymphocyte subsets and their age-associated variation are site-specific. PMID:15500624

  16. Association of Hepatitis C Virus Infection With CD4/CD8 Ratio in HIV-Positive Women

    Science.gov (United States)

    O'Brien, Thomas R.; Prokunina-Olsson, Ludmila; Augenbraun, Michael; Plankey, Michael; Karim, Roksana; Sarkar, Monika; French, Audrey L.; Pierce, Chris; Strickler, Howard D.; Anastos, Kathryn

    2016-01-01

    Background: Recent studies reported that the CD4/CD8 T-cell ratio is inversely associated with biomarkers traditionally used to measure immune activation and systemic inflammation in highly active antiretroviral therapy–treated HIV-infected (HIV+) patients. The relation of hepatitis C virus (HCV) coinfection with the CD4/CD8 ratio in HIV+ patients is unknown. Methods: We examined 50,201 CD4/CD8 ratios measured over 20 years in 3 groups of HIV+ women enrolled in the Women's Interagency HIV Study: HCV antibody negative (n = 1734), cleared HCV (n = 231), and chronic HCV (n = 751) in multivariate models. IFNL4-ΔG genotype and HCV viral load were also considered. Results: Compared with HCV antibody negative status, chronic HCV infection was associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification (β = −0.08; P = 0.002). Cleared HCV (β = −0.10; P = 0.0009), but not IFNL4-ΔG genotype or HCV viral load, was also associated with lower CD4/CD8 ratios when HIV viral load was suppressed to the lower limit of quantification. Conclusions: The association of HCV coinfection with CD4/CD8 ratio is consistent with previously observed associations of HCV coinfection with biomarkers traditionally used to measure immune activation and systemic inflammation in HIV+ patients. These data provide additional support for the use of CD4/CD8 ratio for routine monitoring of immune activation and inflammation in HIV+ patients, including those with HIV/HCV coinfection; however, the unexpected association between cleared HCV and lower CD4/CD8 ratio requires additional study. PMID:27183178

  17. TCR(+)CD3(+)CD4(-)CD8(-) effector T cells in psoriasis.

    Science.gov (United States)

    Brandt, D; Sergon, M; Abraham, S; Mäbert, K; Hedrich, C M

    2017-08-01

    The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR(+)CD3(+)CD4(-)CD8(-) "double negative" (DN) T cells can derive from CD8(+) T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive. We demonstrate that a majority of DN T cells exhibits effector memory phenotypes, express IFN-γ, and fail to proliferate. DN T cells from psoriasis patients are characterized by reduced DNA methylation of the IFNG gene and increased PD-1 expression. Furthermore, PD-1 positive DN T cells infiltrate the epidermis in psoriatic skin lesions. Our observations offer additional insight into the molecular pathophysiology of plaque psoriasis and show promise as potential disease biomarkers and/or therapeutic targets for future interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Productive HIV-1 infection is enriched in CD4(-)CD8(-) double negative (DN) T cells at pleural sites of dual infection with HIV and Mycobacterium tuberculosis.

    Science.gov (United States)

    Meng, Qinglai; Canaday, David H; McDonald, David J; Mayanja-Kizza, Harriet; Baseke, Joy; Toossi, Zahra

    2016-01-01

    A higher human immunodeficiency virus 1 (HIV-1) viral load at pleural sites infected with Mycobacterium tuberculosis (MTB) than in peripheral blood has been documented. However, the cellular source of productive HIV infection in HIV-1/MTB-coinfected pleural fluid mononuclear cells (PFMCs) remains unclear. In this study, we observed significant quantities of HIV-1 p24(+) lymphocytes in PFMCs, but not in peripheral blood mononuclear cells (PBMCs). HIV-1 p24(+) lymphocytes were mostly enriched in DN T cells. Intracellular CD4 expression was detectable in HIV-1 p24(+) DN T cells. HIV-1 p24(+) DN T cells showed lower surface expression of human leukocyte antigen (HLA)-ABC and tetherin than did HIV-1 p24(+) CD4 T cells. Upon in vitro infection of PFMC CD4 T cells from TB mono-infected subjects, Nef- and/or Vpu-deleted HIV mutants showed lower generation of HIV-1 p24(+) DN T cells than the wild-type virus. These data indicate that productively HIV-1-infected DN T cells, generated through down-modulation of surface CD4, likely by HIV-1 Nef and Vpu, are the predominant source of HIV-1 at pleural sites of HIV/MTB coinfection.

  19. Porcine reproductive and respiratory syndrome virus induces CD4+CD8+CD25+Foxp3+ regulatory T cells (Tregs).

    Science.gov (United States)

    Silva-Campa, Erika; Mata-Haro, Verónica; Mateu, Enric; Hernández, Jesús

    2012-08-15

    The aim of this study was to analyze the regulatory T cells (Tregs) induced by the porcine reproductive and respiratory syndrome virus (PRRSV) in pigs. Serum, blood, tonsil, and mediastinal lymph nodes' samples were obtained at different time post-infection (dpi). The frequencies of CD4(+)CD8(-)CD25(+)Foxp3(+), CD4(+)CD8(+)CD25(+)Foxp3(+), or CD4(-)CD8(+)CD25(+)Foxp3(+) phenotypes were determined in PBMC and lymph node cells, and cells producing IL-10 or TGF-β were analyzed. PRRSV increased the number of CD4(+)CD8(+)CD25(+)Foxp3(+) cells at 14 dpi, whereas CD4(+)CD8(-)CD25(+)Foxp3(+) remained constant until 28 dpi. Positive correlation exists between viremia and induced regulatory cells. CD4(+)CD8(+)CD25(+)Foxp3(+)-induced Treg cells were consistently observed in lymphoid tissues. Analysis of IL-10- and TGF-β-producing cell demonstrated that in response to PRRSV, CD4(+)CD8(-)Foxp3(low) and CD4(+)CD8(+)Foxp3(high) cells increase moderately the proportion of IL-10(+) cells. TGF-β was only observed in the CD4(+)CD8(+)Foxp3(high) population after PRRSV stimulation. In conclusion, PRRSV infection increases the frequency of Tregs with the phenotype CD4(+)CD8(+)CD25(+)Foxp3(high) and produces TGF-β. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. TCR engagement of CD4+CD8+ thymocytes in vitro induces early aspects of positive selection, but not apoptosis.

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    Groves, T; Parsons, M; Miyamoto, N G; Guidos, C J

    1997-01-01

    Immature CD4/CD8 double-positive (DP) thymocytes expressing self MHC-restricted TCR are positively selected in response to TCR signals to survive and differentiate into functionally competent CD4 or CD8 single positive (SP) T cells. In contrast, DP precursors expressing autoreactive TCR are clonally deleted in response to TCR signals. We show here that in vitro TCR engagement of TCR(low) DP thymocytes rapidly triggers a variety of events considered to be hallmarks of positive selection in vivo. These include increased expression of CD5 and Bcl-2, termination of RAG-1 and pre-T(alpha) gene expression, and a switch in lck promoter usage. We also demonstrate that CD4- or CD28-mediated signals synergize with TCR signals to induce these outcomes. Finally, we show that the response of DP thymocytes to TCR engagement is selective in that clonal deletion, CD4/CD8 lineage commitment, and other events associated with maturation, such as changes in expression of Thy-1, HSA, MHC class I, and CD45-RB, were not induced. Thus, only subsets of maturational processes associated with positive selection in vivo were shown to be directly coupled to TCR signaling pathways at the DP stage. These observations support conclusions from in vivo systems suggesting that multiple, temporally separated TCR engagements are required to effect the entire spectrum of developmental changes associated with positive selection, and provide a conceptual and experimental framework for unraveling the complexity of positive selection.

  1. Characteristics of TCRαβ+CD4-CD8- thymocytes in fetal thymic organ culture

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    TCRαβ+CD4-CD8- (TCR+ DN) thymocytes at different developmental periods, i.e. after either 9 or 18 days of culture in the fetal thymic organ culture (FTOC) system, were characterized in the properties of phenotype, proliferation, differentiation and apoptosis. The results showed that anti-CD3 mAb significantly promoted proliferation of TCRαβ+ DN cells generated after 18 days of culture in FTOC, whereas the cells generated after 9 days of culture responded to anti-CD3 mAb by proliferation weakly. IL-7 efficiently induced TCRαβ+ DN cells at day 9 of FTOC to differentiate into TCRαβ+CD4+/CD8+ SP cells without detectable transitional stage of TCRαβ+CD4+CD8+ (DP) cells. In contrast, fewer TCRαβ+ DN cells generated after 18 days of FTOC were induced to differentiate into SP cells. The thymic stromal cell line MTEC5 cells synergized with IL-7 to promote the differentiation of TCRαβ+ DN cells. In addition, TCRαβ+ DN cells were shown to be less susceptible to apoptosis compared with the other major thymocyte subsets. Taken together, these data have provided insight into the characteristics of TCRαβ+ DN thymocytes.

  2. Enhanced normalisation of CD4/CD8 ratio with early antiretroviral therapy in primary HIV infection

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    John Thornhill

    2014-11-01

    Full Text Available Introduction: Despite normalization of total CD4 counts, ongoing immune dysfunction is noted amongst those on antiretroviral therapy (ART. Low CD4/CD8 ratio is associated with a high risk of AIDS and non-AIDS events and may act as a marker of immune senescence [1]. This ratio is improved by ART although normalization is uncommon (~7% [2]. The probability of normalization of CD4 count is improved with immediate ART initiation in primary HIV infection (PHI [3]. We examined whether CD4/CD8 ratio similarly normalized in immediate vs. deferred ART at PHI. Material and Methods: Using data from the SPARTAC trial and the UK Register of HIV Seroconverters, we examined the effect of ART with time (continuous from HIV seroconversion (SC on CD4/CD8 ratio (≥1 adjusted for sex, risk group, ethnicity, enrolment from an African site and both CD4 count and age at ART initiation. We also examined that effect by dichotomizing HIV duration at ART initiation (ART started within six months of SC: early ART; ART initiated>six months after SC: deferred. We also considered time to CD4 count normalization (≥900 cells/mm3. Results: In total, 353 initiated ART with median (IQR 97.9 (60.5, 384.5 days from estimated seroconversion; 253/353 early ART, 100 deferred ART. At one year after starting ART, 114/253 (45% early ART had normalized CD4/8 ratio, compared with 11/99 (11% in the deferred group, whilst 83/253 (33% of early ART had normalized CD4 counts, compared with 3/99 (3% in the deferred group. Individuals initiating within six months of PHI were significantly more likely to reach normal ratio than those initiating later (HR, 95% CI 2.96, 1.75 – 5.01, p<0.001. The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.96 – 0.99 for each 30-day increase. CD4 count at ART initiation was also associated with normalization, as expected (HR 1.002, 95% CI 1.001 – 1.002, p<0.001. There was an

  3. Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection.

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    Liu, Ching-Chuan; Huang, Kao-Jean; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng; Lei, Huan-Yao

    2002-10-01

    The immune status after dengue virus infection was studied in dengue patients from an outbreak of serotype 3 dengue virus infection in the southern part of Taiwan during November and December 1998. Consecutive blood samples from 29 dengue patients, of whom 21 had dengue fever and 8 had dengue hemorrhagic fever/dengue shock syndrome, were collected, and the immunophenotypes of the peripheral blood mononuclear cells were determined by flow cytometry. The early activation marker CD69 appeared on lymphocytes and monocytes at day 4 after the onset of fever, and declined afterward. However, a transient reverse in the CD4/CD8 ratio occurred at days 6-10 after the onset of fever. The CD4/CD8 ratio inversion was manifested in 10 of 29 dengue patients and was encountered more frequently in dengue hemorrhagic fever/dengue shock syndrome than in dengue fever patients. Analysis of the clinical blood cell count of these 10 cases showed that increase of immature neutrophils developed at fever days 5-6, CD4(dim) or CD8(dim) monocytosis at days 6-7, and atypical lymphocytosis at days 8-10 after the onset of fever. Serum IL-6 was found at either day 7 or day 9-11. The PHA-stimulated T-cell response was depressed as well. These changes in immune parameters indicate aberrant immune activation during dengue virus infection and might be involved in the pathogenesis of dengue virus infection.

  4. Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India

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    Sharma Gaurav

    2011-01-01

    Full Text Available The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103. The most common oromucosal lesion was erythematous candidiasis (EC (38.8% followed by melanotic hyperpigmentation (35.9%. Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio 20,000 copies/mL (20,000 copies/mL.

  5. Effect of trichloroethylene on the level of CD3+CD4+CD8+lymphocyte in peripheral blood of rats%三氯乙烯对大鼠外周血淋巴细胞CD3+CD4+CD8+的影响

    Institute of Scientific and Technical Information of China (English)

    黄新凤; 徐新云; 李学余; 刘月峰; 周丽

    2011-01-01

    Aim To investigate the effect of trichloroethylene (TCE) on level of CD3+CD4+CD8+ lymphocyte in peripheral blood of rats. Methods Guinea pig maximization test (GPMT) was applied in this study ,rats were divided into negative control group,positive control group and TCE treatment group. Animals in 3 groups were administrated with olive oil, 2,4-dinitrochlorobenzene (DNCB), and TCE, respectively, by intradermal injection. Peripheral blood was collected from the animals for determination of levels of lymphocyte CD3+CD4+CD8+ with flow cytometer. Results The ratio of lymphocyte CD3+ increased in TCE group and positive control group compared to negative control group. The ratio of CD4+ and CD4+/CD8+ elevated in positive control group,but CD8+ decreased in positive control group compared with negative control group. Additionally,the ratio of CD4+ and CD4+/CD8+ did not show any variation in TCE group compared with negative control group. Conclusions Trichloroethylene treatment can affect the ratios of lymphocytes in peripheral blood of rats,it might be associated with trichloroethylene -induced hypersensitivity.%目的 探讨三氯乙烯(TCE)对大鼠外周血淋巴细胞CD3+CD4+CD8+的影响.方法 采用豚鼠最大值法(GPMT),将大鼠随机分为3组,分别为阴性对照组、阳性对照组、TCE实验组,用皮内注射的方式分别注射橄榄油、2,4-二硝基氯苯(DNCB)、三氯乙烯(TCE),实验结束后收集大鼠外周血液.用流式细胞仪检测淋巴细胞CD3+CD4+CD8+比例.结果 TCE实验组和阳性对照组大鼠外周血淋巴细胞CD3+比例高于阴性对照组;阳性对照组CD4+、CD4+/CD8+高于阴性对照组,CD8+ 于对照组,存在显著性差异(P<0.05);TCE实验组CD4%CD8+,CD4+/CD8+与阴性对照组比较无统计学差异.结论 三氯乙烯经皮染毒时大鼠外周血淋巴细胞亚型比例有一定影响,可能与三氯乙烯的致敏作用存在一定关系.

  6. CD4-CD8 differentiation in the thymus: connecting circuits and building memories.

    Science.gov (United States)

    Xiong, Yumei; Bosselut, Rémy

    2012-04-01

    The proper choice of the CD4-helper or CD8-cytotoxic lineages by developing T cells is crucial for the generation of an antigen-responsive and functionally fit T cell repertoire. Here we present a brief overview of the transcriptional control of this process, with emphasis on two issues. The study of Cd4 expression, that had previously generated important paradigms for transcriptional regulation in eukaryotic cells, now brings new twists to the concept of 'epigenetic memory'. And connections are emerging between transcriptional regulators critical for commitment to either lineage. The present review attempts to integrate these findings and discusses the still elusive mechanisms that match CD4-CD8 lineage differentiation to MHC specificity.

  7. Flow Cytometric Analysis of Leishmania Reactive CD4+/CD8+ Lymphocyte Proliferation in Cutaneous Leishmaniasis

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    H Keshavarz

    2008-12-01

    Full Text Available Background: Determination of the division history of T cells in vitro is helpful in the study of effector mechanisms against infections. Technique described here uses the intracellular fluorescent label carboxyfluorescein diacetate succinimidyl ester (CFSE to monitor the proliferation. Methods: In a cross sectional study, blood samples were collected from 7 volunteers with history of cutaneous leishmania­sis (CL and one healthy control from endemic areas in Isfahan province who referred to the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL, then CD4+/CD8+ lymphocytes and CD14+ monocytes were isolated from peri­pheral blood mononuclear cells (PBMC using mAbs and magnetic nanoparticles. CFSE labeled CD4+ or CD8+ lympho­cytes cultured with autologous monocytes in the presence of PHA, SLA, live Leishmania major or as control with­out sti­mulation. Cells were harvested after 7 days and were analyzed using flow cytometry. Results: Five consecutive divisions were monitored separately. Stimulation of CD4+ or CD8+ lymphocytes from CL sub­jects with SLA showed a significant difference in proliferation comparing with unstimulated cells (P< 0.05. The signifi­cant difference in the percentages of CD4+ cells stimulated with SLA was revealed at different divisions for each subject. In CD8+ lymphocyte, significant stronger stimulation of SLA was evident later in the proliferation process. The mean number of divisions in both CD4+/CD8+ lymphocytes stimulated with SLA was significantly greater than when stimulated with live L. major (P=0.007 / P=0.012, respectively Conclusion: The percentage of divided cells might be calculated separately in each division. The cells remained active following CFSE staining and there is possibility of functional analysis simultaneously.

  8. Is an increase in CD4/CD8 T-cell ratio in lymph node fine needle aspiration helpful for diagnosing Hodgkin lymphoma? A study of 85 lymph node FNAs with increased CD4/CD8 ratio

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    Hernandez Osvaldo

    2005-01-01

    Full Text Available Abstract Background An elevated CD4/CD8 T-cell ratio on flow cytometry (FCM analysis has been reported in the literature to be associated with Hodgkin lymphoma (HL. The purpose of our study was to determine the diagnostic significance of an elevated CD4/CD8 ratio in lymph node fine needle aspiration (FNA specimens. Design Between 1996 and 2002, out of 837 lymph node FNAs submitted for flow cytometry analysis, 85 cases showed an elevated CD4/CD8 ratio, defined as greater than or equal to 4, without definitive evidence of a lymphoproliferative disorder. The cytologic diagnoses of these 85 cases were grouped into four categories: reactive, atypical, Hodgkin lymphoma (HL, and non-Hodgkin lymphoma (NHL. Histologic follow-up was available in 17/85 (20% of the cases. Results 5 of the 64 cases in which FCM and cytology did not reveal evidence of a lymphoproliferative disease had tissue follow-up because of persistent lymphadenopathy and high clinical suspicion. 3/5 (60% confirmed the diagnosis of reactive lymphadenopathy. The two remaining cases (40% were positive for lymphoma (1HL, 1NHL. 8/15 cases called atypical on cytology had histologic follow-up. 7/8 (87.5% cases were positive for lymphoma (3HL, 4NHL. 3/4 cases called HL on cytology had tissue follow-up and all 3 (100% confirmed the diagnosis of HL. One case diagnosed as NHL on cytology was found to be a diffuse large B-cell lymphoma. In summary, out of 17 cases with histologic follow-up 4/17 (24% were reactive with CD4/CD8 T-cell ratio of 4.1–29, 7/17 (41% were HLs with CD4/CD8 T-cell ratio of 5.3 – 11, and 6/17 (35% were NHLs with CD4/CD8 T-cell ratio of 4.2 – 14. Conclusion An elevated CD4/CD8 ratio on FCM is a nonspecific finding which may be seen in both reactive and lymphoproliferative disorders. The cytomorphologic features of the smear are more relevant than the sole flow cytometric finding of an elevated CD4/CD8 ratio.

  9. [CD4+, CD8+ AND CD19+ cells in individuals with dyslipidemia].

    Science.gov (United States)

    Pereira de Moura, Jose; Santos Rosa, Manuel; Alves, Vera; Mota Pinto, Anabela; Rodrigues, Victor; Silva, José Manuel; Alves de Moura, J J

    2013-01-01

    Introdução: Os mecanismos imunológicos e inflamatórios têm um papel crucial no desenvolvimento da aterosclerose e na sua tradução clínica. São inúmeros os estudos que procuraram relacionar os mais diversos marcadores inflamatórios – leucócitos, proteína C reactiva, interleucinas, quimiocinas, moléculas de adesão, metaloproteinases, etc – com os factores de risco clássicos da aterosclerose, a formação da placa e os fenómenos clínicos. Não são tantos, que tenhamos conhecimento, os trabalhos que analisaram o comportamento das diversas células mononucleares na fisiopatologia da aterosclerose. Sendo os monócitos/macrófagos e os linfócitos células fundamentais no desencadear e posterior evolução desta doença vascular, procurámos determinar as percentagens das diversas populações celulares periféricas em indivíduos dislipidémicos e em normolipidémicos.Material e Métodos: Por citometria de fluxo, determinámos em indivíduos com dislipidemia e num grupo controlo, as concentrações no sangue periférico dos CD3+, CD4+, CD8+, CD19+, CD56+, CD56CD8+, DN, CD25+, CD26+, CD25CD3+, CD26CD3+, CD25CD26CD3+, CCR5+, CCR5CD3+, CCR5CD4+, HLADR+, HLADRCD4+, HLADRCD8h+, HLADRCD8low+, HLADRCD8+, CD95+, CD95CD95L+, CD3CD95+, CD3CD95L+, CD62L+, CD3CD62L+, CD69+, CD69CD3+ e CD69CD4+. Resultados: Embora na sua grande maioria não tenham sido encontradas diferenças significativas entre os dois grupos de participantes, verificaram-se em algumas populações celulares, resultados que nos mereceram alguns comentários. Neste artigo debruçámo-nos apenas sobre as populações positivas para os CD4, CD8 e CD19.Discussão: A menor concentração das células CD4+ na nossa população de dislipidémicos foi aparentemente inesperada devido ao relacionamento existente entre este tipo celular, os factores de risco e a aterosclerose. Não foram determinados os subtipos Th1 e Th2, nem a população de células reguladoras CD4+CD25+, que poderiam explicar a

  10. Cre-/IoxP-Mediated Recombination between the SIL and SCL Genes Leads to a Block in T-Cell Development at the CD4-CD8- to CD4+CD8+ Transition

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    Yue Cheng

    2007-04-01

    Full Text Available In the most common form of stem cell leukemia (SCL gene rearrangement, an interstitial deletion of 82 kb brings SCL under the control of regulatory elements that normally govern expression of the ubiquitously expressed SCL interrupting locus (SIL gene, which is located directly upstream of SCL. To investigate the effect of this fusion in a mouse model, a bacterial artificial chromosome (BAC clone containing both human SIL and SCL genes was isolated, and IoxP sites were inserted into intron 1 of both the SIL and SCL genes, corresponding to the sites at which recombination occurs in human T-cell acute lymphocytic leukemia patients. This BAC clone was used to generate transgenic SILIoxloxSCL mice. These transgenic mice were subsequently bred to Lck-Cre mice that express the Cre recombinase specifically in the thymus. The BAC transgene was recombined between the two IoxP sites in over 50% of the thymocytes from SILIoxloxSCL/Cre double-transgenic mice, bringing the SCL gene under the direct control of SIL regulatory elements. Aberrant SCL gene expression in the thymus was verified by reverse transcription- polymerase chain reaction. Using FACS analysis, we found that mice carrying both SILIoxloxSCL and Cre transgenes have increased CD4-/CD8- thymocytes compared with transgenenegative mice. In the spleen, these transgenic mice show a marked reduction in the number of mature CD4+ or CD8+ cells. These results demonstrate that conditional activation of SCL under control of SIL regulatory elements can impair normal T-cell development.

  11. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients

    Science.gov (United States)

    Hunt, Peter W.; Huang, Yong; Simoes, Marisol; Lima, Sheila B.; Freire, Marcos S.; Caiaffa-Filho, Helio H.; Hong, Marisa A.; Costa, Dayane Alves; Dias, Juliana Zanatta C.; Cerqueira, Natalia B.; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M.; Kallas, Esper G.

    2016-01-01

    Background HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation–characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity—may influence vaccine response in this population. Methods We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. Results 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV–infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. Conclusions HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio. PMID:27941965

  12. Automated four color CD4/CD8 analysis of leukocytes by scanning fluorescence microscopy using Quantum dots

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    Bocsi, Jozsef; Mittag, Anja; Varga, Viktor S.; Molnar, Bela; Tulassay, Zsolt; Sack, Ulrich; Lenz, Dominik; Tarnok, Attila

    2006-02-01

    Scanning Fluorescence Microscope (SFM) is a new technique for automated motorized microscopes to measure multiple fluorochrome labeled cells (Bocsi et al. Cytometry 2004, 61A:1). The ratio of CD4+/CD8+ cells is an important in immune diagnostics in immunodeficiency and HIV. Therefor a four-color staining protocol (DNA, CD3, CD4 and CD8) for automated SFM analysis of lymphocytes was developed. EDTA uncoagulated blood was stained with organic and inorganic (Quantum dots) fluorochromes in different combinations. Aliquots of samples were measured by Flow Cytometry (FCM) and SFM. By SFM specimens were scanned and digitized using four fluorescence filter sets. Automated cell detection (based on Hoechst 33342 fluorescence), CD3, CD4 and CD8 detection were performed, CD4/CD8 ratio was calculated. Fluorescence signals were well separable on SFM and FCM. Passing and Bablok regression of all CD4/CD8 ratios obtained by FCM and SFM (F(X)=0.0577+0.9378x) are in the 95% confidence interval. Cusum test did not show significant deviation from linearity (P>0.10). This comparison indicates that there is no systemic bias between the two different methods. In SFM analyses the inorganic Quantum dot staining was very stable in PBS in contrast to the organic fluorescent dyes, but bleached shortly after mounting with antioxidant and free radical scavenger mounting media. This shows the difficulty of combinations of organic dyes and Quantum dots. Slide based multi-fluorescence labeling system and automated SFM are applicable tools for the CD4/CD8 ratio determination in peripheral blood samples. Quantum Dots are stable inorganic fluorescence labels that may be used as reliable high resolution dyes for cell labeling.

  13. The CD4/CD8 ratio is associated with coronary artery disease (CAD) in elderly Chinese patients.

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    Gao, Pan; Rong, Hong-Hui; Lu, Ting; Tang, Gang; Si, Liang-Yi; Lederer, James A; Xiong, Wei

    2017-01-01

    The aim of this study was to investigate the relationship between number of circulating T cells and coronary artery disease (CAD) in an elderly Chinese population. A total of 295 elderly inpatients (age≥60) were included in this cross-sectional study. Their clinical and biochemical characteristics were recorded. Patients were divided to two groups: control patients and CAD patients. The risk factors of CAD were explored by binary logistic regression analysis. Compared with control patients, the ratio of CD4 to CD8 T cells was significantly increased in CAD patients. There was no difference in the number of CD3, CD4, and CD8 T cells between the two groups. Multiple logistic regression analysis showed that CAD was independently associated with age, gender, body mass index (BMI), systolic blood pressure (SBP), chronic heart failure (CHF) and the CD4/CD8 ratio. In addition, after adjusting for different clinical parameters (including gender, age, CHF, hypertension, arrhythmia, SBP, and BMI), the risk of CAD was significantly increased in patients with a CD4/CD8 ratio>1.5. There was a strong and independent association between the ratio of CD4/CD8 and CAD in elderly Chinese population. Copyright © 2016. Published by Elsevier B.V.

  14. Study of CD4(+), CD8(+), and natural killer cells (CD16(+), CD56(+)) in children with immune thrombocytopenic purpura.

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    El-Rashedi, Farida Hussein; El-Hawy, Mahmoud Ahmed; Helwa, Mohamed Ahmed; Abd-Allah, Sameh Said

    2017-03-01

    To assess the percentage of CD4(+), CD8(+), and natural killer cells (CD16(+), CD56(+)) in children with immune thrombocytopenic purpura (ITP) at presentation and study their impact on disease chronicity. This case-control study was conducted at the Pediatric Hematology and Oncology Unit, Menoufia University Hospital (tertiary care center in Egypt). The study was held on 30 children presenting with ITP; they were followed-up and classified into two groups: 15 children with acute ITP; and 15 children with chronic ITP. Patients were compared to a group of 15 healthy children of matched age and sex. Measurements of CD4(+), CD8(+), and natural killer cells (CD16(+), CD56(+)) by flow cytometry were assessed and compared in these groups. CD4(+) and CD4(+)/CD8(+) were significantly lower in acute and chronic patients than the control group (p0.05). However, CD8(+) was significantly higher in acute and chronic patients than the control group (p0.05). Natural killer cell percent was significantly lower in acute patients than the control group (p0.05). ITP is associated with immunity dysfunction denoted by the increase in cytotoxic T lymphocytes and the decrease in natural killer cells. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  15. Nef functions in BLT mice to enhance HIV-1 replication and deplete CD4+CD8+ thymocytes

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    Zou Wei

    2012-05-01

    Full Text Available Abstract Background The outcome of untreated HIV-1 infection is progression to AIDS and death in nearly all cases. Some important exceptions are the small number of patients infected with HIV-1 deleted for the accessory gene, nef. With these infections, disease progression is entirely suppressed or greatly delayed. Whether Nef is critical for high levels of replication or is directly cytotoxic remains controversial. The major problem in determining the role of Nef in HIV/AIDS has been the lack of tractable in vivo models where Nef’s complex pathogenic phenotype can be recapitulated. Results Intravenous inoculation (3000 to 600,000 TCIU of BLT humanized mice with HIV-1LAI reproducibly establishes a systemic infection. HIV-1LAI (LAI replicates to high levels (peak viral load in blood 8,200,000 ± 1,800,000 copies of viral RNA/ml, range 3,600,000 to 20,400,000; n = 9 and exhaustively depletes CD4+ T cells in blood and tissues. CD4+CD8+ thymocytes were also efficiently depleted but CD4+CD8- thymocytes were partially resistant to cell killing by LAI. Infection with a nef-deleted LAI (LAINefdd gave lower peak viral loads (1,220,000 ± 330,000, range 27,000 to 4,240,000; n = 17. For fourteen of seventeen LAINefdd-infected mice, there was little to no loss of either CD4+ T cells or thymocytes. Both LAI- and LAINefdd-infected mice had about 8% of total peripheral blood CD8+ T cells that were CD38+HLA-DR+ compared dd-infected mice that lost CD4+ T cells received 600,000 TCIU. All three exhibited peak viral loads over 3,000,000 copies of LAINefdd RNA/ml. Over an extended time course, substantial systemic CD4+ T cell loss was observed for the three mice, but there was no loss of CD4+CD8+ or CD4+CD8- thymocytes. Conclusion We conclude Nef is necessary for elevated viral replication and as a result indirectly contributes to CD4+ T cell killing. Further, Nef was not necessary for the activation of peripheral blood CD8+ T cells following

  16. The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

    Science.gov (United States)

    Spada, Celso; Treitinger, Arício; Reis, Marcellus; Masokawa, Ivete Y; Verdi, Júlio C; Luiz, Magali C; Silveira, Mariete V S; Michelon, Cleonice M; Avila-Junior, Silvio; Gil, lone D O; Ostrowskyl, Stephanie

    2002-05-01

    Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

  17. CD4/CD8 ratio is not predictive of multi-morbidity prevalence in HIV-infected patients but identify patients with higher CVD risk

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    Marianna Menozzi

    2014-11-01

    Full Text Available Background: CD4/CD8=2006. High CVD risk was defined for Framingham Risk Score (FRS≥6. Subclinical CVD was defined using cardiac CT scan for calcium score (CAC≥100. Logistic univariate and multivariable adjusted analysis were performed to assess relationships between variables. Results: Demographic and HIV-specific variables distribution in patients with and without MM are shown in Table 1. Figure 1 shows HANA distribution across CD4/CD8 strata: CVD prevalence only appeared to be higher in patients with no CD4/CD8>0.8.In multivariable analyses CD4/CD8<0.8 was not an independent predictor of MM (OR=1.225, CI 0.891; 1.681, p=0.211 after adjustment for age, gender and BMI. Patients with CD4/CD8<0.8 displayed higher CVD risk but not higher prevalence of subclinical CVD. At multivariable analyses CD4/CD8<0.8 remained predictor of higher CVD risk (OR=0.65, CI 0.47–0.917, p=0.014 after correction for sex, BMI, age strata and HIV infection duration. Conclusions: Low CD4/CD8 ratio was not associated with MM prevalence. Patients with CD4/CD8<0.8 ratio displayed higher prevalence of CVD. At multivariable logistic regression CD4/CD8<0.8 is an independent prepredictor of enhanced CVD risk. This may support role of immune-activation/senescence in the pathogenesis of CVD.

  18. Hesperidin Inhibits Inflammatory Response Induced by Aeromonas hydrophila Infection and Alters CD4+/CD8+ T Cell Ratio

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    Abdelaziz S. A. Abuelsaad

    2014-01-01

    Full Text Available Background. Aeromonas hydrophila is an opportunistic bacterial pathogen that is associated with a number of human diseases. Hesperidin (HES has been reported to exert antioxidant and anti-inflammatory activities. Objectives. The aim of this study was to investigate the potential effect of HES treatment on inflammatory response induced by A. hydrophila infection in murine. Methods. A. hydrophila-infected mice were treated with HES at 250 mg/kg b.wt./week for 4 consecutive weeks. Phagocytosis, reactive oxygen species production, CD4+/CD8+ T cell ratio, and CD14 expression on intestinal infiltrating monocytes were evaluated. The expression of E-selectin and intercellular adhesion molecule 1 on stimulated HUVECs and RAW macrophage was evaluated. Results. Percentage of CD4+ T cells in the intestinal tissues of infected treated mice was highly significantly increased; however, phagocytic index, ROS production, CD8+ T cells percentage, and CD14 expression on monocytes were significantly reduced. On the other hand, HES significantly inhibited A-LPS- and A-ECP-induced E-selectin and ICAM-1 expression on HUVECs and ICAM-1 expression on RAW macrophage. Conclusion. Present data indicated that HES has a potential role in the suppression of inflammatory response induced by A. hydrophila toxins through downmodulation of ROS production and CD14 and adhesion molecules expression, as well as increase of CD4+/CD8+ cell ratio.

  19. Differential in vitro CD4+/CD8+ T-cell response to live vs. killed Leishmania major.

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    Nateghi Rostami, M; Keshavarz Valian, H; Eskandari, S E; Miramin Mohammadi, A; Shahrestani, S T; Sarraf-Nejad, A; Khamesipour, A

    2010-02-01

    Clinical trials of killed Leishmania vaccines showed a limited efficacy compared with leishmanization (LZ). The reason for this difference in protection against cutaneous leishmaniasis (CL) is not known and in vivo studies on T-cell function may provide valuable information. Nevertheless, there are limited studies on the nature of the stimulatory effects of live vs. killed parasites on human T cells in vitro. A total of nine Leishmanin Skin Test+ volunteers with a history of self-healing CL (HCL) and seven healthy volunteers were included in this study. 5,6-carboxyfluroescein diacetate succinimidyl ester-labelled CD4(+)/CD8(+) lymphocytes were cultured with killed Leishmania Lysate (Killed LL) or live Leishmania major (Live LM) and analysed for proliferation using flow cytometry. Culture supernatants were used for cytokine titration. In HCL volunteers, upon stimulation with killed LL, the number of proliferated CD4(+)/CD8(+) cells was significantly more than that of unstimulated (P live LM stimulated (P Live LM (P Live LM induced significantly (P Live LM. Cells from HCL volunteers showed significantly more IL-10 production to Live LM stimulation compared with that of controls (CD4(+): P Live LM induced cytokine production without significant induction of proliferation. The results from healed CL volunteers in this study could be implicated in further studies on T-cell response in vaccinated individuals.

  20. CD4:CD8 Lymphocyte Ratio as a Quantitative Measure of Immunologic Health in HIV-1 Infection: Findings from an African Cohort with Prospective Data

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    Jianming eTang

    2015-07-01

    Full Text Available In individuals with human immunodeficiency virus type 1 (HIV-1 infection, CD4:CD8 lymphocyte ratio is often recognized as a quantitative outcome that reflects the critical role of both CD4+ and CD8+ T-cells in HIV-1 pathogenesis or disease progression. Our work aimed to first establish the dynamics and clinical relevance of CD4:CD8 ratio in a cohort of native Africans and then to examine its association with viral and host factors, including: (i length of infection, (ii demographics, (iii HIV-1 viral load (VL, (iv change in CD4+ T-lymphocyte count (CD4 slope, (v HIV-1 subtype, and (vi host genetics, especially human leukocyte antigen (HLA variants. Data from 499 HIV-1 seroconverters with frequent (monthly to quarterly follow-up revealed that CD4:CD8 ratio was stable in the first three years of infection, with a modest correlation with VL and CD4 slope. A relatively normal CD4:CD8 ratio (>1.0 in early infection was associated with a substantial delay in disease progression to severe immunodeficiency (1.0, but HLA variants (e.g., HLA-B*57 and HLA-B*81 previously associated with VL and/or CD4 trajectories in eastern and southern Africans had no obvious impact on CD4:CD8 ratio. Collectively, these findings suggest that CD4:CD8 ratio is a robust measure of immunologic health with both clinical and epidemiological implications.

  1. Microbiota-specific CD4CD8αα Tregs: role in intestinal immune homeostasis and implications for IBD

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    Guillaume eSARRABAYROUSE

    2015-10-01

    Full Text Available In studies in murine models, active suppression by IL-10-secreting Foxp3 regulatory T cells (Tregs has emerged as an essential mechanism in colon homeostasis. However, the role of the equivalent subset in humans remains unclear, leading to suggestions that other subsets and/or mechanisms may substitute for Foxp3 Tregs in the maintenance of colon homeostasis. We recently described a new subset of CD4CD8αα T cells reactive to the gut bacterium Faecalibacterium prausnitzii and endowed with regulatory/suppressive functions. This subset is abundant in the healthy colonic mucosa, but less common in that of patients with irritable bowel disease (IBD. We discuss here the physiological significance and potential role of these Tregs in preventing inflammation of the gut mucosa and the potential applications of these discoveries for IBD management.

  2. Transgenic expression of microRNA-181d augments the stress-sensitivity of CD4(+CD8(+ thymocytes.

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    Serkan Belkaya

    Full Text Available Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+CD8(+ thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs in the thymus upon systemic stress induced by lipopolysaccharide (LPS or the synthetic glucocorticoid, dexamethasone (Dex. MiRs are short, non-coding RNAs that play critical roles in the immune system by targeting diverse mRNAs, suggesting that their modulation in the thymus in response to stress could impact thymopoiesis. MiR-181d is one such stress-responsive miR, exhibiting a 15-fold down-regulation in expression. We utilized both transgenic and gene-targeting approaches to study the impact of miR-181d on thymopoiesis under normal and stress conditions. The over-expression of miR-181d in developing thymocytes reduced the total number of immature CD4(+CD8(+ thymocytes. LPS or Dex injections caused a 4-fold greater loss of these cells when compared with the wild type controls. A knockout mouse was developed to selectively eliminate miR-181d, leaving the closely spaced and contiguous family member miR-181c intact. The targeted elimination of just miR-181d resulted in a thymus stress-responsiveness similar to wild-type mice. These experiments suggest that one or more of three other miR-181 family members have overlapping or compensatory functions. Gene expression comparisons of thymocytes from the wild type versus transgenic mice indicated that miR-181d targets a number of stress, metabolic, and signaling pathways. These findings demonstrate that selected miRs enhance stress-mediated thymic involution in vivo.

  3. Transgenic expression of microRNA-181d augments the stress-sensitivity of CD4(+)CD8(+) thymocytes.

    Science.gov (United States)

    Belkaya, Serkan; van Oers, Nicolai S C

    2014-01-01

    Physiological stress resulting from infections, trauma, surgery, alcoholism, malnutrition, and/or pregnancy results in a substantial depletion of immature CD4(+)CD8(+) thymocytes. We previously identified 18 distinct stress-responsive microRNAs (miRs) in the thymus upon systemic stress induced by lipopolysaccharide (LPS) or the synthetic glucocorticoid, dexamethasone (Dex). MiRs are short, non-coding RNAs that play critical roles in the immune system by targeting diverse mRNAs, suggesting that their modulation in the thymus in response to stress could impact thymopoiesis. MiR-181d is one such stress-responsive miR, exhibiting a 15-fold down-regulation in expression. We utilized both transgenic and gene-targeting approaches to study the impact of miR-181d on thymopoiesis under normal and stress conditions. The over-expression of miR-181d in developing thymocytes reduced the total number of immature CD4(+)CD8(+) thymocytes. LPS or Dex injections caused a 4-fold greater loss of these cells when compared with the wild type controls. A knockout mouse was developed to selectively eliminate miR-181d, leaving the closely spaced and contiguous family member miR-181c intact. The targeted elimination of just miR-181d resulted in a thymus stress-responsiveness similar to wild-type mice. These experiments suggest that one or more of three other miR-181 family members have overlapping or compensatory functions. Gene expression comparisons of thymocytes from the wild type versus transgenic mice indicated that miR-181d targets a number of stress, metabolic, and signaling pathways. These findings demonstrate that selected miRs enhance stress-mediated thymic involution in vivo.

  4. CD4/CD8 Ratio in Mediastinal Lymph Nodes Involved by Sarcoidosis: Analysis of Flow Cytometry Data Obtained by Endobronchial Ultrasound-guided Transbronchial Needle Aspiration.

    Science.gov (United States)

    Ruiz, Sory J; Zhang, Yaxia; Mukhopadhyay, Sanjay

    2016-10-01

    Despite mixed results in the literature, some clinicians continue to consider an elevated CD4/CD8 ratio in bronchoalveolar lavage (BAL) fluid to be supportive of a diagnosis of sarcoidosis. However, the CD4/CD8 ratio in mediastinal lymph nodes involved by sarcoidosis has not been extensively studied. The primary aim of this study was to evaluate the utility of the CD4/CD8 ratio in mediastinal lymph node aspirates obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for diagnosing sarcoidosis. Our archives were searched for EBUS-TBNAs in which mediastinal lymph node aspirates had been submitted for flow cytometry (n=160). Clinical and pathologic findings in these cases were reviewed retrospectively. Cases were included in the study if they had (1) a clinical diagnosis of sarcoidosis supported by cytopathologic confirmation of non-necrotizing granulomas in EBUS-TBNA-derived lymph node aspirates (23 cases), or (2) a pathologically confirmed non-neoplastic diagnosis other than sarcoidosis (7 cases). Cases that did not fulfil these criteria were excluded (130 cases). The CD4/CD8 ratios in mediastinal lymph nodes and BAL fluid were compared. The CD4/CD8 ratio was elevated in mediastinal lymph nodes in 12/23 (52%) cases of sarcoidosis and 3/7 (43%) pathologically confirmed nonsarcoid cases. BAL fluid had been concurrently submitted for flow cytometry in 20/23 cases of sarcoidosis and 5/7 nonsarcoid cases. CD4/CD8 was elevated in BAL fluid in 9/20 (45%) cases of sarcoidosis and 2/5 (40%) nonsarcoid cases. As in BAL fluid, the CD4/CD8 ratio in mediastinal lymph nodes involved by sarcoid granulomas is highly variable and does not reliably confirm or exclude sarcoidosis.

  5. Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice.

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    Ryosuke Tateishi

    Full Text Available Gravity change affects many immunological systems. We investigated the effects of hypergravity (2G on murine thymic cells. Exposure of mice to 2G for three days reduced the frequency of CD4+CD8+ thymocytes (DP and mature medullary thymic epithelial cells (mTECs, accompanied by an increment of keratin-5 and keratin-8 double-positive (K5+K8+ TECs that reportedly contain TEC progenitors. Whereas the reduction of DP was recovered by a 14-day exposure to 2G, the reduction of mature mTECs and the increment of K5+K8+ TEC persisted. Interestingly, a surgical lesion of the inner ear's vestibular apparatus inhibited these hypergravity effects. Quantitative PCR analysis revealed that the gene expression of Aire and RANK that are critical for mTEC function and development were up-regulated by the 3-day exposure and subsequently down-regulated by the 14-day exposure to 2G. Unexpectedly, this dynamic change in mTEC gene expression was independent of the vestibular apparatus. Overall, data suggest that 2G causes a temporary reduction of DP and a persistent reduction of mature mTECs in a vestibular system-dependent manner, and also dysregulates mTEC gene expression without involving the vestibular system. These data might provide insight on the impact of gravity change on thymic functions during spaceflight and living.

  6. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients

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    Wei Lu

    2015-06-01

    Full Text Available Introduction: Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. Method: We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. Discussion: Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. Conclusion: The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune

  7. Recirculation of lymphocyte subsets (CD5+, CD4+, CD8+, T19+ and B cells) through fetal lymph nodes.

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    Kimpton, W G; Washington, E A; Cahill, R N

    1989-01-01

    The experiments reported in this paper examine the cell-surface phenotype (CD5, CD4, CD8, T19, MHC class II and sIg) and cell output of lymphocyte subsets circulating through a subcutaneous lymph node in the sheep fetus, in an environment unaffected by foreign antigen and circulating immunoglobulins. CD4+ lymphocytes were the major T-cell subset in fetal lymph and were clearly enriched in lymph compared with blood, whereas T19+, CD8+ and B lymphocytes were not. It seems likely that in the fetus CD4+ lymphocytes are extracted from the blood at a faster rate than are other T-cell subsets and B cells. There was a much higher percentage of CD8+ and T null cells and a lower percentage of MHC class II+ and B cells circulating in the fetal lymph than in adult lymph, while the percentage of T19+ lymphocytes in fetal blood was twice that in the adult. Although the hourly cell output from an adult prescapular lymph node was far higher than that from a fetal lymph node, the circulation of lymphocytes through fetal lymph nodes was much greater per gram lymph node weight than that through adult lymph nodes. The wholesale recirculation in the fetus of all the major T-cell subsets found in the adult is paradoxical because it is not known what function they serve in the fetus in the absence of antigen and ongoing immune responses, although clearly they are not memory cells. PMID:2481644

  8. Origin Use of CD4, CD8, and CD1a Immunostains in Distinguishing Mycosis Fungoides from its Inflammatory Mimics: A Pilot Study

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    Rajalakshmi Tirumalae

    2012-01-01

    Full Text Available Patch-stage/early mycosis fungoides (MF is difficult to differentiate from benign dermatoses, despite several robust histologic criteria. Most studies include advanced lesions and data about early disease is limited. Objectives: (1 To compare the CD4:CD8 ratio in patch-stage MF versus inflammatory mimics. (2 To study patterns of CD1a expression in the epidermis and dermis in the two groups. Materials and Methods: Twenty cases each of early MF and inflammatory dermatoses were selected. The diagnoses were established after clinicopathologic correlation, repeat biopsies, and follow-up. The inflammatory group included pityriasis lichenoides chronica, actinic reticuloid, lichenoid purpura, and various psoriasiform dermatoses. Immunohistochemistry was done for CD4, CD8, and CD1a. Epidermal CD4, CD8 cells were quantified and CD1a was graded semi-quantitatively in the epidermis and dermis. Results: The average CD4:CD8 ratio was 4.2 in MF (range: 1-16.8, and 0.9 in inflammatory diseases (range: 0.43-5, which was statistically significant (P 1. CD1a cells had a continuous or confluent epidermal pattern in almost all cases of MF, while they occurred as small or large groups in the dermis. In inflammatory dermatoses, there were either isolated or scattered CD1a+ cells in both epidermis and dermis. Conclusions: Elevated CD4:CD8 ratio favors MF. But there is an overlap in the lower range with pityriasis lichenoides chronica. These cases require good clinicopathologic correlation and follow-up. Patterns of CD1a expression are more reliable. Immunostains buttress morphology and are a valuable addition.

  9. Are Mucosa CD4+/CD8+ T-Cells Expressions Correlated with the Endoscopic Appearance of Chronic Gastritis Related with Helicobacter pylori Infection?

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    Neneng Ratnasari

    2016-06-01

    Full Text Available Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h1 cytokine-producing CD4+ and CD8+T-cells Objective. To investigate the correlation between CD4+/CD8+ T-cells in gastric mucosa with endoscopic appearance in chronic gastritis with or without H.pylori infection. Prospective, cross sectional study is performed in a chronic dyspepsia population in July-November 2009 at Dr. Sardjito General Hospital Yogyakarta, Indonesia. The update Sydney system was used to analyze the gastroscopy appearance. Biopsy specimens were stained with HE-stain and IHC-stain. Data were analyzed by t-test, Mann-Whitney and Spearman correlation test. Number of 88 consecutive subjects are enrolled the study (50% male; 50% female, age 46±15 years; 25% H.pylori positive. The expression of CD4+ and CD8+ were higher in H.pylori negative subjects, but only the CD4+ was significant (P=0.011. A significant correlation was found between CD4+ and CD8+ in both subjects (r(Hp+=0.62 and r(Hp-=0.68; P<0.05. The expression of CD4+ and CD8+ in H.pylori positive showed a significant correlation with gastric lesions (r(CD4+=-0.60; r(CD8+=-0.42 ; P<0.05, only erosion showed a significant difference in both subjects. A positive correlation was found between CD4+ and CD8+ infiltration in both subjects with or without H.pylori infection, and a negative correlation was only found between gastric lesion with CD4+ and CD8+ infiltration in H.pylori subject.

  10. Are Mucosa CD4+/CD8+ T-Cells Expressions Correlated with the Endoscopic Appearance of Chronic Gastritis Related with Helicobacter pylori Infection?

    Science.gov (United States)

    Ratnasari, Neneng; Bayupurnama, Putut; Maduseno, Sutanto; Indrarti, Fahmi; Triwikatmani, Catharina; Harijadi, Achmad; Nurdjanah, Siti

    2016-06-01

    Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h)1 cytokine-producing CD4+ and CD8+T-cells Objective. To investigate the correlation between CD4+/CD8+ T-cells in gastric mucosa with endoscopic appearance in chronic gastritis with or without H.pylori infection. Prospective, cross sectional study is performed in a chronic dyspepsia population in July-November 2009 at Dr. Sardjito General Hospital Yogyakarta, Indonesia. The update Sydney system was used to analyze the gastroscopy appearance. Biopsy specimens were stained with HE-stain and IHC-stain. Data were analyzed by t-test, Mann-Whitney and Spearman correlation test. Number of 88 consecutive subjects are enrolled the study (50% male; 50% female), age 46±15 years; 25% H.pylori positive. The expression of CD4+ and CD8+ were higher in H.pylori negative subjects, but only the CD4+ was significant (P=0.011). A significant correlation was found between CD4+ and CD8+ in both subjects (r(Hp+)=0.62 and r(Hp-)=0.68; P<0.05). The expression of CD4+ and CD8+ in H.pylori positive showed a significant correlation with gastric lesions (r(CD4+)=-0.60; r(CD8+)=-0.42 ; P<0.05), only erosion showed a significant difference in both subjects. A positive correlation was found between CD4+ and CD8+ infiltration in both subjects with or without H.pylori infection, and a negative correlation was only found between gastric lesion with CD4+ and CD8+ infiltration in H.pylori subject.

  11. CD4+/CD8+ T lymphocytes imbalance in children with severe 2009 pandemic influenza A (H1N1 pneumonia

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    Ji Eun Kim

    2011-05-01

    Full Text Available Purpose : This study was conducted to investigate the immune responses of children with moderate and severe novel influenza A virus (H1N1 pneumonia, and to compare their clinical and immunological findings with those of control subjects. Methods : Thirty-two admitted patients with H1N1 pneumonia were enrolled in the study. The clinical profiles, humoral and cell-mediated immune responses of the 16 H1N1 pneumonia patients who were admitted to the pediatric intensive care unit (severe pneumonia group, 16 H1N1 pneumonia patients admitted to the pediatric general ward (moderate pneumonia group and 13 control subjects (control group were measured. Results : Total lymphocyte counts were significantly lower in patients with H1N1 pneumonia than in the control group (P=0.02. The number of CD4+ T lymphocytes was significantly lower in the severe pneumonia group (411.5±253.5/μL than in the moderate pneumonia (644.9±291.1/μL, P=0.04 and control (902.5±461.2/μL, P=0.01 groups. However, the number of CD8+ T lymphocytes was significantly higher in the severe pneumonia group (684.2±420.8/μL than in the moderate pneumonia (319.7±176.6/μL, P=0.02 and control (407.2±309.3/μL, P=0.03 groups. The CD4+/CD8+ T lymphocytes ratio was significantly lower in the severe pneumonia group (0.86±0.24 than in the moderate pneumonia (1.57±0.41, P=0.01 and control (1.61±0.49, P=0.01 groups. The serum levels of immunoglobulin G, immunoglobulin M and immunoglobulin E were significantly higher in the severe pneumonia group than in the 2 other groups. Conclusion : The results of this study suggest that increased humoral immune responses and the differences in the CD4+ and CD8+ T lymphocyte profiles, and imbalance of their ratios may be related to the severity of H1N1 pneumonia in children.

  12. Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Hjelmborg, J v B; Christensen, Per B

    2003-01-01

    clinical course, with significantly higher 5-year survival, p=0.046, independent of the Dukes stage and age. Our results have implications for tumour immunology; colorectal cancer cells might be a target for cytotoxic T-lymphocytes, however the tumour cells are not able to initiate an immune response......The purpose of this study was to clarify whether HLA-DR expression of colorectal tumour cells or the CD4+/CD8+ ratio of the tumour infiltrating lymphocytes is significantly associated with the prognosis of colorectal cancer. Using flow cytometry, we studied the tumour cell expression of the HLA...... class II in 70 enzymatically dissociated colorectal cancers and the phenotype of tumour infiltrating lymphocytes (TILs) in 41 cases. There was no trend in 5-year survival between three levels (low, medium, high) of HLA-DR expression on the tumour cells. Patients with low CD4+/CD8+ ratios had a better...

  13. Percentage of CD4+, CD8+, and CD25+ T lymphocytes in peripheral blood of pigs in the course of experimental burns and necrectomy

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    Aleksiewicz Roman

    2015-09-01

    Full Text Available The aim of the study was the evaluation of changes in the percentage profile of CD4+, CD8+, and CD25+ T lymphocytes, and their predictive value with respect to the course of experimental skin burns and early necrectomy in pigs. Thirty Large White Landrace pigs of both genders, weighing 50 kg (±2 kg, were used. Burns to their skin were performed with the use of a computer-controlled heating plate, applied to the animal’s body and heated to 2000°C, using 2.5 kg pressure for 10 s. It produced a burn of 30% (±2% of body surface with a range of damage between II b° and III°. In animals of each experimental group fascial necrectomy was performed, according to the testing module. Blood from experimental and non-treated control animals was collected from the external jugular vein before the beginning of the experiment (hour 0 and at 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 h of the experiment. An immune response profile was evaluated using flow cytometry analysis of the level and expression dynamics of CD4+, CD8+, and CD25+ particles on the surface of T lymphocytes. The study demonstrated that experimentally-induced burns in pigs caused cell-mediated immune response reflected in the changes in the percentage of CD4+, CD8+, and CD25+ T lymphocytes, and that early necrectomy in burnt pigs acted in a protective manner for the organism, based on the immunological index values. The study also proved that the dynamics of cell-mediated immunological response intensification determined on the basis of the percentage of CD4+, CD8+, and CD25+ T lymphocytes is conditioned by the size of the burnt surface and the time of necrectomy procedure.

  14. A study of T CD4, CD8 and B lymphocytes in narcoleptic patients Estudo dos linfócitos T CD4, CD8 e B em pacientes com narcolepsia

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    Fernando Morgadinho Santos Coelho

    2007-06-01

    Full Text Available Narcolepsy is characterized by excessive daytime sleep and cataplexy. Little is known about the possible difference in pathophysiology between patients with or without cataplexy. OBJECTIVE: To quantify T CD4, T CD8 and B lymphocytes in subgroups of patients with narcolepsy and the presence or absence of the HLA-DQB1*0602 allele between groups. METHOD: Our study was prospective and controlled (transversal with 22 narcoleptic patients and 23 health control subjects. Patients underwent an all-night polysomnographic recording (PSG and a multiple sleep latency Test (MSLT. The histocompatibility antigen allele (HLA-DQB1*0602, T CD4, CD8 and B lymphocytes were quantified in control subjects and in narcoleptics. RESULTS: The HLA-DQB1*0602 allele was identified in 10 (62.5% of our 16 cataplexic subjects and in 2 (33.3% of the 6 patients without cataplexy (p=0.24. In control subjects, HLA-DQB1*0602 allele was identified in 5 (20%. A significant decrease in T CD4 and B lymphocytes was found in narcoleptic patients with recurrent cataplexy when compared with our patients without cataplexy. CONCLUSION: Autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis were associated with a decrease in sub-group of T CD4 and B lymphocytes. A drop in B lymphocytes count in reumathoid arthritis might, it is posited, be correlated to the presence of HLA-DRB1 allele along with an overall worsened outcome of the affliction. The theory of an increase in consumption of B lymphocytes over the maturation phase has likewise been put forward. Our study reinforces the view that narcolepsy should be considered from an immunological perspective.A narcolepsia é caracterizada por sonolência excessiva diurna e cataplexia. Pouco se sabe sobre as diferenças fisiopatológicas entre pacientes com e sem cataplexia. OBJETIVO: Quantificar os linfócitos T CD4, T CD8 e B e a presença do alelo HLA-DQB1*0602 nos subgrupos de pacientes com narcolepsia. MÉTODO: O

  15. Pulmonary toxicity of polyvinyl chloride particles after repeated intratracheal instillations in rats. Elevated CD4/CD8 lymphocyte ratio in bronchoalveolar lavage.

    Science.gov (United States)

    Xu, Haiyan; Vanhooren, Hadewijch M; Verbeken, Erik; Yu, Lisong; Lin, Yuan; Nemery, Benoit; Hoet, Peter H M

    2004-01-15

    Occupational exposure to polyvinyl chloride (PVC) particles has been associated with interstitial lung disease. Our previous study showed that a single intratracheal instillation of emulsion PVC particles, with or without residual additives, induces acute but transient alveolitis in a dose-dependent manner in rats. The aim of the present study was to investigate the pulmonary response after the administration of the same PVC particles (PVC-E3 and PVC-W3) given in the same cumulative doses (10 and 50 mg/kg BW), but fractionated as seven intratracheal instillations (7 x 1.4 and 7 x 7.1 mg/kg BW) in the course of 3 weeks (day 0 to day 21). Pulmonary response was characterized by analysis of lung weight, bronchoalveolar lavage (BAL) fluid for lactate dehydrogenase (LDH), total protein, and cell cytology, and a microscopic evaluation of lung tissue. BAL T lymphocyte phenotypes (CD3 + CD4 +, CD3 + CD8+) were analyzed by flow cytometry. On day 28, lung weights, BAL-LDH, cell numbers in BAL, and CD4/CD8 ratios in BAL T lymphocytes were higher in rats that had received the high dose of PVC-E3 or PVC-W3 than in rats that had received the low dose of PVC particles and control rats. On day 90, the pulmonary response had partially regressed towards control values, but there were still microscopically evident lesions in the lungs and greater CD4/CD8 ratio in the high dose groups. There were significant positive correlations between the CD4/CD8 ratio and a histopathology score of the lung (r = 0.36, P = 0.038 on day 28, and r = 0.46, P = 0.006 on day 90). In conclusion, repeated intratracheal instillations of PVC particles yielded similar results as single instillations. The examined PVC particles have the potential of inducing a limited and transient acute inflammatory reaction in the lung, and possibly a more persistent alteration of pulmonary T lymphocyte subsets towards a high CD4/CD8 ratio.

  16. Decreased signaling competence as a result of receptor overexpression: overexpression of CD4 reduces its ability to activate p56lck tyrosine kinase and to regulate T-cell antigen receptor expression in immature CD4+CD8+ thymocytes.

    OpenAIRE

    Nakayama, T.; Wiest, D L; Abraham, K.M.; Munitz, T I; Perlmutter, R M; Singer, A

    1993-01-01

    Thymic selection of the developing T-cell repertoire occurs in immature CD4+CD8+ thymocytes, with the fate of individual thymocytes determined by the specificity of T-cell antigen receptor they express. However, T-cell antigen receptor expression in immature CD4+CD8+ thymocytes is actively down-regulated in CD4+CD8+ thymocytes by CD4-mediated tyrosine kinase signals that are generated in the thymus as a result of CD4 engagement by intrathymic ligands. In the present study we have examined the...

  17. Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

    Science.gov (United States)

    Nesti, M; Carli, E; Giaquinto, C; Rampon, O; Nastasio, S; Giuca, M R

    2012-01-01

    This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of

  18. Effects of housefly maggots extracts on the proliferation and the CD4+/CD8+ ratio of mouser splenic lymphocytes in vitro%罗仙子提取物对小鼠脾淋巴细胞的体外增殖及CD4+/CD8+比例的影响

    Institute of Scientific and Technical Information of China (English)

    许银叶; 褚夫江; 吴玉萍; 金小宝; 朱家勇

    2013-01-01

    目的 研究罗仙子提取物(housefly maggots extracts,HME)对正常小鼠脾淋巴细胞的体外增殖,以及对小鼠淋巴细胞亚群CD4+/CD8+比例的影响.方法 不同浓度的罗仙子提取物对刀豆蛋白A(concanavalin A,ConA)体外处理的小鼠脾T淋巴细胞作用,初步确定其发挥作用的最佳浓度.采用MTT法检测罗仙子提取物在不同的时间点对ConA诱导的小鼠脾淋巴细胞的增殖能力,运用流式细胞仪检测细胞周期的分布以及CD4+/CD8+比例.结果 罗仙子提取物浓度为40 μg/mL,作用48 h后,能明显促进ConA 诱导的小鼠脾淋巴细胞增殖,并且能降低G0/G1期细胞的百分比以及升高S期和G2/M期细胞的百分比,并以48 h效果最明显.能使CD4+、CD4+/CD8+比例降低.结论 罗仙子可能通过免疫调节作用影响动脉粥样硬化.%Objective To study the effects of housefly maggots extracts ( HME ) on the proliferation and the CD4+/CD8+ ration of mouse splenic lymphocytes in vitro. Methods Mouse splenic lymphocytes stimulated by con-canavalin A ( ConA ) were treated with different concentrations of HME. The effects of splenocyte proliferation were assessed by MTT in order to select the most effective concentration of HME. Using the most effective concentration, splenic lymphocytes were treated with HME at different time points. Splenocyte cell cycle distribution and the CIM + /CD8 + ratio were observed by flow cytometry. Results HME of 40μg/mL notabty promoted the proliferation of splenic lymphocyte after cultivation for 48 hours, reduced the G0/G1 phase cells and raised the S and G2/M phase cells. HME could also reduced the CD4+ , CD8 + and CD4 + /CD8+ ratio. Conclusion HME regulates immue functions in atherosclerosis.

  19. Coinfection by Hepatitis C Is Strongly Associated with Abnormal CD4/CD8 Ratio in HIV Patients under Stable ART in Salvador, Brazil

    Directory of Open Access Journals (Sweden)

    Clara Brites-Alves

    2015-01-01

    Full Text Available Proper immune restoration (CD4 count >500 and normal CD4/8 ratio is reached only by a fraction of HIV patients, despite stable viral suppression. Methods. We present a case-control study to compare HIV patients with viral suppression >1 year, according to immune restoration pattern: adequate response (AR defined by CD4 > 500 cells/mm3 and CD4/8 ratio >1; partial response (PR = patients with CD4 > 500, but CD4/8 ratio <1; inadequate response (IR = CD4 < 500 cells. Results. We evaluated 293 consecutive patients (89 AR, 112 PR, and 92 IR, 70% males. Male gender (p<0.01, lower mean CD4 nadir (p<0.001, higher baseline VL (p=0.01, previous diagnosis of Tb (p=0.03, or HCV (p<0.01 was associated with IR. Likelihood of AR/PR was similar regardless of gender, after adjusting for nadir CD4+ cells count. Longer time under suppressive ART was also associated with a greater chance of AR, but logistic regression identified coinfection by HCV as the main factor associated with abnormal CD4/CD8 ratio. Conclusion. Early initiation of ART and longer time since first undetectable PVL were predictors of AR. Previous HCV diagnosis significantly increases the risk of abnormal CD4/CD8 ratio.

  20. Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.

    LENUS (Irish Health Repository)

    Tinago, Willard

    2014-01-01

    Although effective antiretroviral therapy(ART) increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+\\/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+\\/CD8+ ratio have not been well described.

  1. [Aging and influence of inversion of the CD4:CD8 ratio in the incidence of co-morbidities and mortality in a cohort of patients infected with human immunodeficiency virus].

    Science.gov (United States)

    Cervero, Miguel; Torres, Rafael; Agud, Jose Luis; Pastor, Susana; Jusdado, Juan José

    2016-03-04

    It has been postulated that the inversion of the CD4:CD8 ratio as a hallmark of immunosenescence can be an independent factor that can herald the risk of co-morbidities. We studied the influence of aging and inversion of the CD4:CD8 ratio in the incidence of comorbidities and mortality in the cohort of Hosptital Severo Ochoa. We analyzed the differences in the incidence rates of age-adjusted morbidities and evaluated the inversion of the CD4:CD8 ratio as predictor of mortality and development of comorbidities. Age was associated with an increased incidence rate of diabetes mellitus, fractures, COPD and non-AIDS malignancies. We found an increased incidence rate of non-AIDS clinical events (OR 2.25; 95% CI 1.025-4.94) and AIDS events (OR 3.48; 95% CI 1.58-7.64) in individuals with CD4:CD8 ratio<0.7. Moreover, patients with a CD4:CD8 ratio<0.7 ratio had a higher risk of mortality (OR 5.96; 95% CI 0.73 to 48.40). It is important to detect and prevent non-AIDS comorbidities in the presence of a CD4:CD8 ratio<0.7. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  2. Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naive and memory T-cell subsets.

    Directory of Open Access Journals (Sweden)

    Willard Tinago

    Full Text Available BACKGROUND: Although effective antiretroviral therapy(ART increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+/CD8+ ratio have not been well described. METHODS: A cross-sectional study in a cohort of ambulatory HIV+ patients. We used flow cytometry on fresh blood to determine expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+(central memory, CD45RO+CD62L-(effector memory and CD45RO-CD62L+(naïve alongside routine T-cell subsets(absolute, percentage CD4+ and CD8+ counts, HIVRNA and collected demographic and treatment data. Relationship between CD4+/CD8+ T-cell ratio and expanded T-cell subsets was determined using linear regression analysis. Results are median[IQR] and regression coefficients unless stated. RESULTS: We recruited 190 subjects, age 42(36-48 years, 65% male, 65.3% Caucasian, 91% on ART(52.6% on protease inhibitors, 78.4% with HIVRNA1. Of the expanded CD4+ T-cell subsets, 27.3(18.0-38.3% were naïve, 36.8(29.0-40.0% central memory and 27.4(20.0-38.5% effector memory. Of the CD8+ T-cells subsets, 16.5(10.2-25.5% were naïve, 19.9(12.7-26.6% central memory and 41.0(31.8-52.5% effector memory. In the multivariable adjusted analysis, total cumulative-ART exposure(+0.15,p = 0.007, higher nadir CD4+ count(+0.011,p1 had significantly higher median %CD8+ naive T-cells; 25.4(14.0-36.0% versus 14.4(9.4-21.6%, p<0.0001, but significantly lower absolute CD8+ count; 464(384.5-567 versus 765(603-1084 cells/mm3, p<0.001. CONCLUSIONS: Study suggests important role for naïve CD8+ T-cell populations in normalisation of the immune response to HIV-infection. How these findings relate to persistent immune activation on ART requires further study.

  3. Combined application of CFSE labeling and flow cytometry on the detection of the proliferation of CD4+/CD8+ T cells simulated with monocytes Siglec-1%CFSE标记结合流式细胞术检测单核细胞Siglec-1刺激CD4+/CD8+T细胞增殖

    Institute of Scientific and Technical Information of China (English)

    熊怡淞; 俞娟; 孙懿; 李畅; 仲人前

    2011-01-01

    目的 建立CFSE标记结合流式细胞术检测T淋巴细胞增殖的方法,并探讨其在研究单核细胞唾液酸黏附素(Siglec-1)对CD4+/CD8+ T细胞增殖中的应用.方法 免疫磁珠分离冠状动脉综合征(ACS)患者和健康对照者外周血CD14+单核细胞,与经CFSE标记的第三方健康献血者CD4+/CD8+ T细胞共培养5 d,流式细胞术检测T淋巴细胞增殖情况.结果 ACS患者CD14+单核细胞具有比健康人单核细胞更强的刺激CD4+/CD8+ T淋巴细胞增殖能力;当用干扰素-α(INF-α)刺激增强正常单核细胞Siglec-1表达后,其刺激T细胞增殖能力增强;用单抗阻断单核细胞Siglec-1后,其刺激T细胞增殖能力减弱.结论 ACS患者增强的CD4+/CD8+ T淋巴细胞增殖能力部分是由于激活的单核细胞高表达Siglec-1引起.%Objective To establish a combined detection method of CFSE labeling and flow cytometry (FCM) for the measurement of the proliferation of T lymphocytes and to explore its role for the investigation of the effect of Siglec-1 in monocytes on the proliferation of CD4+/CD8+ T cells.Methods CD14 + monocytes in peripheral blood of patients with acute coronary syndrome (ACS) and healthy controls were isolated by magnetic-activated cell sorting (MACS).CD4+ and CD8+ T cells from healthy blood donors of third-party were also separated by MACS and labeled with CFSE.5 days after the mixed culture of monocytes and lymphocytes, the proliferation of T lymphocyte was determined by FCM.Results CD14+ monocytes from patients with ACS had a more robust role in stimulating the proliferation of CD4 /CD8 T lymphocyte than those from healthy controls.However, when Siglec-1 on monocytes was blocked by anti-Siglec-1 antibody,the stimulating capacity was decreased to normal level.Furthermore,after being stimulated with INF-α,the expression of Siglec-1 on monocytes from healthy controls was elevated and the stimulating capacity of monocytes was enhanced.Conclusion The increased

  4. Detection of CD4+/CD8+T Lymphocyte Ratio and CD4+CD25+ Treg in Peripheral Blood of Patients with Sporadic Vitiligo%散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+T细胞的检测

    Institute of Scientific and Technical Information of China (English)

    叶蓉; 马刚; 胡小平; 彭曦

    2012-01-01

    目的 检测散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+调节性T细胞水平,探讨其与散发型白癜风发病的关系.方法 散发型白癜风患者29例,男13例,女16例.通过流式细胞仪对散发型白癜风患者外周血CD4+/CD8+T细胞比值及CD4+CD25+调节性T细胞水平进行检测,并与20例健康人相比较.结果 与健康对照组相比,散发型白癜风患者外周血中CD4+/CD8+T细胞比值的差异无统计学意义(P>0.05),而CD4+CD25+调节性T细胞水平明显减少,差异有统计学意义(P<0.05),但在不同病程的患者中CD4+CD25+调节性T细胞数量的差异无统计学意义(P>0.05).结论 散发型白癜风患者外周血中存在CD4+CD25+调节性T细胞水平下降,可能与散发型白癜风的发生发展有一定关系.%Objective To detect the CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level in peripheral blood of patients with sporadic vitiligo, and to investigate its role in the pathogenesis of sporadic vitiligo. Methods Peripheral blood samples were taken from 29 outpatients with sporadic vitiligo, including 13 males and 16 females. The CD4+/CD8+ T lymphocyte ratio and the CD4+CD25+ Treg level was detected in peripheral blood of patients with sporadic vitiligo by flow cytometry, as well as controlled samples from 20 healthy human. Results There was no difference on the ratio of CD4+/CD8+ T lymphocyte between the patients with sporadic vitiligo and healthy people (P>0.05). Compared to the controlled group, the proportion of CD4+CD25+ Treg was significantly lower in sporadic vitiligo patients(P0.05). Conclusion The level of CD4+CD25+ Treg is lower in peripheral blood of sporadic vitiligo patients, which might play a role in the pathogenesis and development of sporadic vitiligo.

  5. Correlation between CD4, CD8 cell infiltration in gastric mucosa,Helicobacter pylori infection and symptoms in patients with chronic gastritis

    Institute of Scientific and Technical Information of China (English)

    Ai-Ping Lu; Sheng-Sheng Zhang; Qing-Lin Zha; Da-Hong Ju; Hao Wu; Hong-Wei Jia; Cheng Xiao; Shao Li; Hui Jian

    2005-01-01

    AIM: To evaluate the correlation between CD4, CD8 cell infiltration in gastric mucosa, Helicobacter pylori(H pylori)infection and symptoms or the assemblage of symptoms in cases with chronic gastritis.METHODS: Biopsy samples at the gastric antrum were obtained from 62 patients with chronic gastritis. CD4 and CD8 cell infiltration was evaluated by immunohistochemical assays on frozen sections of the biopsy samples. Fifteen symptoms referring to digestion-related activity and nondigestion related activity were observed. The correlation between lymphocyte infiltration and each symptom or symptom assemblage was analyzed by logistic regression and K-mean cluster methods.RESULTS: CD4 cell infiltrations in gastric mucosa were much more in patients with H pylori infection, while CD8 cell infiltrations were similar in patients with or without H pylori infection. Logistic regression analysis showed that the symptoms including heavy feeling in head or body (t= 2.563), and thirst (t= 2.478) were significantly related with CD4 cell infiltration in gastric mucosa (P<0.05), and cool limbs with aversion to cold were related with CD8cell infiltration (t = 2.872, P<0.05). Further analysis showed that non-digestive related symptom assemblage could increase the predicted percentage of CD4 and CD8cell infiltration in gastric mucosa, including lower CD4infiltration by 12.5%, higher CD8 infiltration by 33.3%,and also non-H pylori infection by 23.6%.K-means cluster analysis of all symptoms and CD4 and CD8 cell infiltration in gastric mucosa showed a similar tendency to increase the predicted percentage of CD4, CD8 cell infiltration and H pylori infection.CONCLUSION: Based on correlation between the gastric mucosa lymphocyte infiltration, H pylori infection and clinical symptoms, symptoms or symptomatic assemblages play an important role in making further classification of chronic gastritis, which might help find a more specific therapy for chronic gastritis.

  6. CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    2014-04-01

    Full Text Available How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL-10-producing Foxp3 regulatory T cells (Treg, which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL and peripheral blood lymphocytes (PBL from healthy individuals, and those with colon cancer and irritable bowel disease (IBD, we demonstrated that CD4CD8αα (DP8α T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8α LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8α PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii identify F. prausnitzii as a major inducer of these Treg, (iii argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv provide new tools to address the systemic impact of both these Treg

  7. HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

    Directory of Open Access Journals (Sweden)

    Sergio Serrano-Villar

    2014-05-01

    Full Text Available A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3 is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+ and senescence (CD28- and CD57+CD28-, and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years. After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.

  8. Regulation of T cell receptor expression in immature CD4+CD8+ thymocytes by p56lck tyrosine kinase: basis for differential signaling by CD4 and CD8 in immature thymocytes expressing both coreceptor molecules

    OpenAIRE

    1993-01-01

    Signals transduced through the T cell antigen receptor (TCR) are modulated by the src family tyrosine kinase p56lck (lck), which associates in mature T cells with the coreceptor molecules CD4 and CD8. Here we describe a novel function of lck in immature CD4+CD8+ thymocytes, that of regulating TCR expression. Activation of lck in immature CD4+CD8+ thymocytes by intrathymic engagement of CD4 maintains low TCR expression by causing most TCR components to be retained and degraded within the endop...

  9. Flavivirus-cross-reactive, HLA-DR15-restricted epitope on NS3 recognized by human CD4+ CD8- cytotoxic T lymphocyte clones.

    Science.gov (United States)

    Kurane, I; Okamoto, Y; Dai, L C; Zeng, L L; Brinton, M A; Ennis, F A

    1995-09-01

    The role of flavivirus-cross-reactive T lymphocytes in recovery from and pathogenesis of flavivirus infections is not known. In the present paper, we have defined a flavivirus-cross-reactive epitope recognized by two CD4+ CD8- cytotoxic T lymphocyte (CTL) clones, JK4 and JK43. The T cell clones were established from the peripheral blood T lymphocytes of a dengue-4-immune donor, using a limiting-dilution method with dengue-4 antigen. These two T cell clones were cross-reactive for dengue virus types 1, 2, 3 and 4, yellow fever virus and West Nile virus, and recognized NS3 protein. The smallest synthetic peptide recognized by these T cell clones was an identical 9 amino acid peptide which contains amino acids 146 to 154 (VIGLYGNGV) of dengue-4 NS3. HLA-DR15 was the restriction allele for recognition of this epitope by JK4 and JK43. JK4 and JK43 both used T cell receptor V alpha 8, but JK4 used V beta 8 and JK43 used V beta 2. This result indicates that this epitope is recognized by two flavivirus-cross-reactive CD4+ T cell clones which originated from different T cells in vivo.

  10. Increased percentage of L-selectin+ and ICAM-1+ peripheral blood CD4+/CD8+ T cells in active Graves' ophthalmopathy.

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    Alina Bakunowicz-Lazarczyk

    2009-05-01

    Full Text Available The purpose of the study was to evaluate the percentage of CD4+/CD8+ peripheral T cells expressing CD62L+ and CD54+ in patients with Graves' disease and to assess if these estimations could be helpful as markers of active ophthalmopathy. The study was carried out in 25 patients with Graves' disease (GD divided into 3 groups: 1/ 8 patients with active Graves' ophthalmopathy (GO (CAS 3-6, GO complaints pound 1 year, 2/ 9 patients with hyperthyroid GD without symptoms of ophthalmopathy (GDtox and 3/ 8 patients with euthyroid GD with no GO symptoms (GDeu. The control group consisted of 15 healthy volunteers age and sex matched to groups 1-3. The expression of lymphocyte adhesion molecules was evaluated by using three-color flow cytometry. In GO group the percentage of CD8+CD54+, CD8+CD62L+, CD4+CD54+ and CD4+CD62L+ T cells was significantly higher as compared to controls (p<0.001, p<0.05, p<0.01, p<0.001 respectively. The percentage of CD8+CD54+ T lymphocytes was also elevated in GO group in comparison to hyperthyroid GD patients (p< 0.05. CD4+CD62L+ and CD8+CD54+ percentages were also increased in GDtox and GDeu as compared to controls. We found a positive correlation between the TSHRab concentration and the percentage of CD8+CD62L+ T cells in all studied groups (r= 0.39, p<0.05 and between the TSHRab level and CAS (r= 0.77, p<0.05. The increased percentage of CD8+CD54+ and CD8+CD62L+ T cells in patients with Graves' ophthalmopathy may be used as a marker of immune inflammation activity.

  11. Concentrations of IL-15, IL-18, IFN-γ and activity of CD4(+), CD8(+) and NK cells at admission in children with viral bronchiolitis.

    Science.gov (United States)

    Grześk, Elżbieta; Kołtan, Sylwia; Dębski, Robert; Wysocki, Mariusz; Gruszka, Marzena; Kubicka, Małgorzata; Kołtan, Andrzej; Grześk, Grzegorz; Manysiak, Sławomir; Odrowąż-Sypniewska, Grażyna

    2010-09-01

    The pathogenesis of viral bronchiolitis is poorly understood. The aim of this study was to analyze interleukin (IL)-15, IL-18 and interferon (IFN)-γ concentrations and the activity of NK cells and CD4(+) and CD8(+) lymphocytes in 23 children not older than 30 months of age with acute viral bronchiolitis using blood samples drawn within the first 24 h of their hospital admission, in comparison to a healthy group. In children with bronchiolitis, the mean concentrations of IL-15, IL-18 and IFN-γ were 9.39±11.55, 884.03±645.44 and 17.92±27.14 pg/ml, respectively, and were significantly higher than those in the control group [2.34±0.61 pg/ml (p<0.05), 248.69±98.73 pg/ml (p<0.001) and 2.75±1.72 pg/ml (p<0.005), respectively]. In the bronchiolitis group, mean z-scores were -1.15±1.9 for CD4(+) cells and -0.9±1.23 for CD8(+) cells; these scores were significantly lower than those of the general Polish population (p<0.001 and <0.01, respectively). However, the mean z-score of the ratio of CD4(+)/CD8(+) and the NK cell count in children with bronchiolitis did not differ significantly from those of the controls. In conclusion, cytokines such as IL-15, IL-18 and IFN-γ play a role in the pathogenesis of bronchiolitis in children.

  12. CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC).

    Science.gov (United States)

    Trickey, Adam; May, Margaret T; Schommers, Philipp; Tate, Jan; Ingle, Suzanne M; Guest, Jodie L; Gill, M John; Zangerle, Robert; Saag, Mike; Reiss, Peter; Monforte, Antonella d'Arminio; Johnson, Margaret; Lima, Viviane D; Sterling, Tim R; Cavassini, Matthias; Wittkop, Linda; Costagliola, Dominique; Sterne, Jonathan A C

    2017-09-15

    We investigated whether CD4:CD8 ratio and CD8 count were prognostic for all-cause, AIDS, and non-AIDS mortality in virologically suppressed patients with high CD4 count. We used data from 13 European and North American cohorts of human immunodeficiency virus-infected, antiretroviral therapy (ART)-naive adults who started ART during 1996-2010, who were followed from the date they had CD4 count ≥350 cells/μL and were virologically suppressed (baseline). We used stratified Cox models to estimate unadjusted and adjusted (for sex, people who inject drugs, ART initiation year, and baseline age, CD4 count, AIDS, duration of ART) all-cause and cause-specific mortality hazard ratios for tertiles of CD4:CD8 ratio (0-0.40, 0.41-0.64 [reference], >0.64) and CD8 count (0-760, 761-1138 [reference], >1138 cells/μL) and examined the shape of associations using cubic splines. During 276526 person-years, 1834 of 49865 patients died (249 AIDS-related; 1076 non-AIDS-defining; 509 unknown/unclassifiable deaths). There was little evidence that CD4:CD8 ratio was prognostic for all-cause mortality after adjustment for other factors: the adjusted hazard ratio (aHR) for lower vs middle tertile was 1.11 (95% confidence interval [CI], 1.00-1.25). The association of CD8 count with all-cause mortality was U-shaped: aHR for higher vs middle tertile was 1.13 (95% CI, 1.01-1.26). AIDS-related mortality declined with increasing CD4:CD8 ratio and decreasing CD8 count. There was little evidence that CD4:CD8 ratio or CD8 count was prognostic for non-AIDS mortality. In this large cohort collaboration, the magnitude of adjusted associations of CD4:CD8 ratio or CD8 count with mortality was too small for them to be useful as independent prognostic markers in virally suppressed patients on ART.

  13. 中国HIV/AIDS患者CD+4 CD+8T淋巴细胞与外周血各组份间关系的研究%Study on the relationship between values of CD4,CD8 and the components of peripheral blood in people living with HIV/AIDS in China

    Institute of Scientific and Technical Information of China (English)

    肖瑶; 张可; 裴丽健; 王鹏; 张辉; 冯基刚; 吴昊; 蒋岩

    2004-01-01

    目的研究艾滋病病毒/艾滋病(HIV/AIDS)患者CD+4、CD+8T淋巴细胞数与外周血各组份间白细胞(WBC)、血小板(PLT)、血红蛋白(HGB)、粒细胞百分数(GR%)、淋巴细胞百分数(LY%)、LY的相关性,为临床治疗提供参考依据.方法 HIV/AIDS患者抗凝外周血513份,在6小时之内检测其血细胞分类和CD+4、CD+8T淋巴细胞计数,比较CD+4、CD+8T淋巴细胞计数与WBC、HGB、PLT、LY%、GR%和LY的相关性.结果 CD4/CD8全部倒置,其中CD4/CD8<1者达94.7%;CD+4细胞数<500/mm3与HGB(r=0.160,P<0.01)、PLT(r=-0.014,P<0.01)、GR%(r=-0.281,P<0.01)、LY%(r=0.321,P<0.01)、LY((r=0.494,P<0.01)相关均有非常显著的统计学意义;CD+8细胞数与WBC数(r=0.112,P<0.05)、HGB(r=0.131,P<0.01)、GR%(r=-0.526,P<0.01)、LY%(r=0.569,P<0.01)、LY(r=0.904,P<0.01)相关均有显著性;200/mm3<CD+4细胞数<500/mm3与LY(r=0.279,P<0.01)、PLT(r=0.192,P<0.01)相关有显著性,CD+4细胞数<200/mm3与LY(r=0.262,P<0.01)、LY%(r=0.279,P<0.01)、GR%(r=-0.294,P<0.01)相关有显著性.结论 HIV/AIDS患者CD+4、CD+8T淋巴细胞数与外周血中HGB、LY%、LY呈正相关,与GR%呈负相关.CD4/CD8与HGB、PLA、LY相关无显著性.

  14. The Effect of Resveratrol Combined with Tacrolimus on CD4+/CD8+ T Cells in Rat Renal Allografts%白藜芦醇联合他克莫司对大鼠移植肾CD4+/CD8+T细胞的影响

    Institute of Scientific and Technical Information of China (English)

    钱坤; 龙建华; 蒋鸿涛

    2014-01-01

    Objective: To investigate the effect of resveratrol(RES) combined with tacrolimus(FK506)on CD4+/CD8+ T cells in rats renal allografts, and assess the possibility that RES synergizes FK506 based immunosuppressant, thus acting as an clinical immunosuppressive combination to promote renal allograft survival and function.Method: Renal allogenic grafting was performed on BN rats as donors and LEW rats as recipients. Forty-eight male LEW rats were randomly divided into four groups: control group(n=12), RES group(n=12), FK506 group(n=12), FK506+RES group(n=12), and then interventions were made from day 1 before renal transplantation (RTx). In each group, survival lengths of rats(n=6) were recorded in each group after RTx, and also CD4+ and CD8+ T-cell infiltration in renal grafts of rats(n=6) were analyzed by immunohistochemistry on day 6 after RTx.Result: Renal allograft survival in FK506+RES group was markedly prolonged as compared to other groups, and the difference were all statistically significant(P<0.05). A significant decrease of CD4+ and CD8+ T cells infiltration into the graft was demonstrated in FK506+RES group as compared to other groups, and the difference were all statistically significant(P<0.05).Conclusion: RES and FK506 exert synergistic effect towards markedly decreasing CD4+ and CD8+ T cells infiltration into the graft of rat, decreasing rejection, and further enhancing rat renal allograft survival. We hypothesized that novel therapeutic approaches involving combination of RES with FK506 will produce potential beneficial outcomes in clinical renal transplantation.%目的:观察白藜芦醇(RES)联合他克莫司(FK506)对大鼠移植肾CD4+/CD8+T细胞的影响,探讨将RES应用于肾移植领域的价值。方法:以BN大鼠为供体,LEW大鼠为受体,建立大鼠同种异体肾移植模型。将48只受体大鼠按照随机数字表法均分为对照组、RES组、FK506组、RES+FK506组,术前1 d开始进行药物干预。记录每组6

  15. Dengue virus-specific, human CD4+ CD8- cytotoxic T-cell clones: multiple patterns of virus cross-reactivity recognized by NS3-specific T-cell clones.

    OpenAIRE

    Kurane, I; Brinton, M.A.; Samson, A L; Ennis, F A

    1991-01-01

    Thirteen dengue virus-specific, cytotoxic CD4+ CD8- T-cell clones were established from a donor who was infected with dengue virus type 3. These clones were examined for virus specificity and human leukocyte antigen (HLA) restriction in cytotoxic assays. Six patterns of virus specificities were determined. Two serotype-specific clones recognized only dengue virus type 3. Two dengue virus subcomplex-specific clones recognized dengue virus types 2, 3, and 4, and one subcomplex-specific clone re...

  16. Ex Vivo Restimulation of Human PBMC Expands a CD3+CD4-CD8-γδ+ T Cell Population That Can Confound the Evaluation of CD4 and CD8 T Cell Responses to Vaccination

    Directory of Open Access Journals (Sweden)

    B. J. Sedgmen

    2013-01-01

    Full Text Available The measurement of vaccine-induced humoral and CD4+ and CD8+ cellular immune responses represents an important correlate of vaccine efficacy. Accurate and reliable assays evaluating such responses are therefore critical during the clinical development phase of vaccines. T cells play a pivotal role both in coordinating the adaptive and innate immune responses and as effectors. During the assessment of cell-mediated immunity (CMI in subjects participating in a large-scale influenza vaccine trial, we identified the expansion of an IFN-γ-producing CD3+CD4-CD8-γδ+ T cell population in the peripheral blood of 90/610 (15% healthy subjects. The appearance of CD3+CD4-CD8-γδ+ T cells in the blood of subjects was transient and found to be independent of the study cohort, vaccine group, subject gender and ethnicity, and ex vivo restimulation conditions. Although the function of this population and relevance to vaccination are unclear, their inclusion in the total vaccine-specific T-cell response has the potential to confound data interpretation. It is thus recommended that when evaluating the induction of IFN-γ-producing CD4+ and CD8+ immune responses following vaccination, the CD3+CD4-CD8-γδ+ T cells are either excluded or separately enumerated from the overall frequency determination.

  17. Efflux Transporters Regulate Arsenite Induced Genotoxicity in Double Negative and Double Positive T Cells.

    Science.gov (United States)

    Xu, Huan; Medina, Sebastian; Lauer, Fredine T; Douillet, Christelle; Jian Liu, Ke; Hudson, Laurie G; Stýblo, Miroslav; Aleksunes, Lauren M; Burchiel, Scott W

    2017-04-29

    Arsenite (As+3) exposure is known to cause immunotoxicity in human and animal models. Our previous studies demonstrated that As+3 at 50 to 500 nM concentrations induced both genotoxicity and non-genotoxicity in mouse thymus cells. Developing T cells at CD4-CD8- double negative (DN) stage, the first stage after early T cells are transported from bone marrow to thymus, were found to be more sensitive to As+3 toxicity than the T cells at CD4+CD8+ double positive (DP) stage in vitro. Induction of Mdr1 (Abcb1) and Mrp1 (Abcc1), two multidrug resistance transporters and exporters of As+3, was associated with the reversal of As+3-induced double strand breaks and DNA damage. In order to confirm that the thymus cell populations have different sensitivity to As+3in vivo, male C57BL/6J mice were exposed to 0, 100 and 500 ppb As+3 in drinking water for 30 d. A significant decrease in DN cell percentage was observed with exposure to 500 ppb As+3. Low to moderate concentrations of As+3 were shown to induce higher genotoxicity in sorted DN cells than DP cells in vitro. Calcein AM uptake and Mdr1/Mrp1 mRNA quantification results revealed that DN cells not only had limited As+3 exporter activity, but also lacked the ability to activate these exporters with As+3 treatments, resulting in a higher accumulation of intracellular As+3. Knockdown study of As+3 exporters in the DN thymic cell line, D1 using siRNA, demonstrated that Mdr1 and Mrp1 regulate intracellular As+3 accumulation and genotoxicity. Taken together, the results indicate that transporter regulation is an important mechanism for differential genotoxicity induced by As+3 in thymocytes at different developmental stages. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. HIV单独感染与合并HBV、HCV感染CD4+、CD8+T淋巴细胞计数及CD4+/CD8+对比分析

    Institute of Scientific and Technical Information of China (English)

    罗静蓉; 李山; 邓燕; 彭契六; 莫翠菊; 刘燕琼; 陈学杰

    2015-01-01

    目的:研究HIV感染合并HBV、HCV感染者外周血CD4+、CD8+T淋巴细胞计数变化,探讨合并感染对HIV感染者细胞免疫功能的影响.方法:收集已确诊的HIV阳性感染者血样259份,并对HIV单独感染者、HIV/HBV合并感染者、HIV/HCV合并感染者及HIV/HBV/HCV合并感染者的CD4+、CD8+T淋巴细胞数、CD4+/CD8+比值进行比较分析.结果:在259例HIV感染者中,HIV/HBV合并感染者72例,占27.8%;HIV/HCV合并感染者8例,占3.1%;HIV/HBV/HCV合并感染者3例,占1.2%;与HIV单独感染者比较,HIV/HBV、HIV/HBV/HCV合并感染者CD8+T淋巴细胞数差异有统计学意义(P<0.05);与HIV单独感染者比较,HIV/HBV、HIV/HCV、HIV/HBV/HCV合并感染者CD4+T淋巴细胞数、CD4+/CD8+比值差异均无统计学意义(均P>0.05).结论:HIV感染者合并HBV感染可能增强了机体的免疫应答.

  19. Reversal of the CD4(+)/CD8(+) T-cell ratio in lymph node cells upon in vitro mitogenic stimulation by highly purified, water-soluble S3-S4 dimer of pertussis toxin.

    Science.gov (United States)

    Latif, R; Kerlero de Rosbo, N; Amarant, T; Rappuoli, R; Sappler, G; Ben-Nun, A

    2001-05-01

    Pertussis toxin (PT), a holomer consisting of a catalytic S1 subunit and a B oligomer composed of S2-S4 and S3-S4 dimers, held together by the S5 subunit, exerts profound effects on immune cells, including T-cell mitogenicity. While the mitogenic activity of PT was shown to reside fully within the B oligomer, it could not be assigned to any particular B-oligomer component. In this study, we purified the S3-S4 dimer to homogeneity under conditions propitious to maintenance of the native conformation. In contrast to previous reports which suggested that both S3-S4 and S2-S4 dimers are necessary for mitogenic activity, our preparation of the highly purified S3-S4 dimer was as strongly mitogenic as the B oligomer, suggesting that the S3-S4 dimer accounts for the mitogenic activity of the B oligomer. Moreover, in vitro stimulation of naive lymphocytes by the S3-S4 dimer resulted in reversal of the normal CD4(+)/CD8(+) T-cell ratio from approximately 2:1 to 1:2. The reversal of the CD4(+)/CD8(+) T-cell ratio is unlikely to be due to preferential apoptosis-necrosis of CD4(+) T cells, as indicated by fluorescence-activated cell sorter analysis of annexin-stained T-cell subsets, or to preferential stimulation of CD8(+) T cells. The mechanism underlying the reversal requires further investigation. Nevertheless, the data presented indicate that the S3-S4 dimer may have potential use in the context of diseases amenable to immunological modulation.

  20. Multidimensional Clusters of CD4+T Cell Dysfunction Are Primarily Associated with the CD4/CD8 Ratio in Chronic HIV Infection

    DEFF Research Database (Denmark)

    Frederiksen, Juliet Wairimu; Buggert, Marcus; Noyan, Kajsa

    2015-01-01

    was compared to a multidimensional clustering tool, FLOw Clustering with K (FLOCK) in two cohorts of 47 untreated HIV-infected individuals and 21 age and sex matched healthy controls. In order to reduce the subjectivity of FLOCK, we developed an "artificial reference", using 2% of all CD4+ gated T cells from......HIV infection provokes a myriad of pathological effects on the immune system where many markers of CD4+ T cell dysfunction have been identified. However, most studies to date have focused on single/double measurements of immune dysfunction, while the identification of pathological CD4+ T cell...... clusters that is highly associated to a specific biomarker for HIV disease remain less studied. Here, multi-parametric flow cytometry was used to investigate immune activation, exhaustion, and senescence of diverse maturation phenotypes of CD4+ T cells. The traditional method of manual data analysis...

  1. CD4 T cell control primary measles virus infection of the CNS: regulation is dependent on combined activity with either CD8 T cells or with B cells: CD4, CD8 or B cells alone are ineffective.

    Science.gov (United States)

    Tishon, Antoinette; Lewicki, Hanna; Andaya, Abegail; McGavern, Dorian; Martin, Lee; Oldstone, Michael B A

    2006-03-30

    Measles virus (MV), one of the most infectious of human pathogens, still infects over 30 million humans and causes over 500,000 deaths each year [Griffin, D., 2001. Measles virus. In: Fields, B., Knipe, D., Howley, P. (Eds.), Fields Virology. Lippincott-Raven, Philadelphia, pp. 1401-1442; ]. Death is primarily due to secondary microbial infections associated with the immunosuppression caused by MV. Studies of humans with genetic or acquired deficiencies of either the humoral or cellular arm of the immune system, and rodent models have implicated T cells in the control of the ongoing MV infection but the precise role and activities of the specific T cell subset or the molecules they produce is not clear. Using a transgenic mouse model in conjunction with depletion and reconstitution of individual B and T cell subsets alone or in combination, we show that neither CD4, CD8 nor B cells per se control acute MV infection. However, combinations of either CD4 T cells and B cells, or of CD4 and CD8 T cells are essential but CD8 T with B cells are ineffective. Interferon-gamma and neutralizing antibodies, but neither perforin nor TNF-alpha alone are associated with clearance of MV infection. TNF-alpha combined with interferon-gamma is more effective in protection than interferon alone. Further, the lack of an interferon-gamma response leads to persistence of MV.

  2. 新生儿感染时CD64、CD3、CD4、CD8的表达研究%Neonatal infection CD64, CD3, CD4, CD8 expression studies

    Institute of Scientific and Technical Information of China (English)

    王丽丽; 刘光辉; 郑洪

    2014-01-01

    目的:探讨新生儿感染时外周血CD64及CD3、CD4、CD8的表达,为新生儿细菌感染的早期诊断和细菌感染时细胞免疫功能的评价提供循证支持。方法应用流式细胞仪定量检测120例感染和非感染新生儿外周血CD64分子及CD3、CD4、CD8的表达变化,并将败血症组患儿的CD64与C反应蛋白(CRP)、白细胞计数及血培养进行比较。结果败血症组CD64为(6.7±2.8),高于局部感染组(4.1±1.4)与非感染组(2.9±0.5),差异有统计学意义(P0.05),各组间CD8差异无统计学意义(P>0.05)。结论 CD64可作为新生儿细菌感染的早期诊断指标,严重细菌感染患儿存在细胞免疫功能紊乱,T淋巴细胞亚群检测对新生儿细胞免疫功能的评价有重要意义。%Objective To investigate neonatal infection in peripheral blood CD64 and CD3, CD4, CD8 expression for the early diagnosis of neonatal bacterial infection and bacterial infection celular immune function evaluation of evidence-based support. Methods 120 cases of flow cytometry detection of neonatal infection and non-infected peripheral blood CD64 molecule and CD3, CD4, CD8 expression changes, and sepsis in children with CD64 and C-reactive protein (CRP), white blood cellcount and blood training for comparison. Result CD64 as a result of sepsis group (6.7±2.8), higher than the local infection group (4.1±1.4) and non-infected group (2.9±0.5), the difference was statisticaly significant (P0.05), CD8 difference between the groups was not statisticaly significant (P>0.05). Conclusion CD64 can be used as an early diagnosis of neonatal bacterial infection indicators of serious bacterial infections in children with immune dysfunction, T lymphocyte subsets in the newborn immune function evaluation is important.

  3. The Role and Mechanisms of Double Negative Regulatory T Cells in the Suppression of Immune Responses

    Institute of Scientific and Technical Information of China (English)

    WenhaoChen; MeganS.Ford; KevinJ.Young; LiZhang

    2004-01-01

    Accumulating evidence has demonstrated that regulatory T (Treg) cells play an important role in the maintenance of immunologic self-tolerance and in down-regulating various immune responses. Thus, there has recently been an increasing interest in studying the biology of Treg cells as well as their potential application in treating immune diseases. Many types of Treg cell subsets have been reported in a variety of disease models.Among these subsets, αβ-TCR+CD3+CD4*CD8* double negative (DN) Treg cells are defined by their capability of inhibiting immune responses via directly killing effector T cells in an antigen specific fashion. Furthermore,DN Treg cells have been shown to develop regulatory activity after encountering specific antigens, partially mediated by the acquisition of MHC-peptide complexes from antigen presenting cells (APCs). The presentation of acquired alloantigens on DN T cells allows for the specific interaction between DN Treg cells and alloantigen reactive effector T cells. Once the DN Treg and target cells have come into contact, killing is then mediated by Fas/Fas-ligand interactions, and perhaps through other unidentified pathways. Further characterization of the functions, molecular expression and mechanisms of activation of DN Treg cells will help in the development of novel therapies to induce antigen specific tolerance to self and foreign antigens. Cellular & Molecular Immunology. 2004;1(5):328-335.

  4. The Role and Mechanisms of Double Negative Regulatory T Cells in the Suppression of Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Wenhao Chen; Megan S. Ford; Kevin J. Young; Li Zhang

    2004-01-01

    Accumulating evidence has demonstrated that regulatory T (Treg) cells play an important role in the maintenance of immunologic self-tolerance and in down-regulating various immune responses. Thus, there has recently been an increasing interest in studying the biology of Treg cells as well as their potential application in treating immune diseases. Many types of Treg cell subsets have been reported in a variety of disease models.Among these subsets, αβ-TCR+CD3+CD4-CD8- double negative (DN) Treg cells are defined by their capability of inhibiting immune responses via directly killing effector T cells in an antigen specific fashion. Furthermore,DN Treg cells have been shown to develop regulatory activity after encountering specific antigens, partially mediated by the acquisition of MHC-peptide complexes from antigen presenting cells (APCs). The presentation of acquired alloantigens on DN T cells allows for the specific interaction between DN Treg cells and alloantigen reactive effector T cells. Once the DN Treg and target cells have come into contact, killing is then mediated by Fas/Fas-ligand interactions, and perhaps through other unidentified pathways. Further characterization of the functions, molecular expression and mechanisms of activation of DN Treg cells will help in the development of novel therapies to induce antigen specific tolerance to self and foreign antigens. Cellular & Molecular Immunology. 2004;1(5):328-335.

  5. Retinol as a micronutrients related to cervical local immunity: The expression of tumor necrosis factor-alpha specifically stimulated with E6 epitope of human papillomavirus type-16 and ratio of CD4+/CD8+ T cell in natural history of cervical cancer

    Science.gov (United States)

    Utami, T. W.; Aziz, M. F.; Ibrahim, F.; Andrijono

    2017-08-01

    Retinol is one of the antioxidant micronutrients that plays essential roles in the immune system, by preventing the persistence of modulating CD4+ and CD8+ T cells and cytokines production. Tumor Necrosis Factor-Alpha (TNF-α) is an acute pro-inflammatory cytokine which has many crucial roles in controlling HPV. In contrast, when persistent infection occurs, TNF-α induces carcinogenesis. The ratio of CD4+ cells to CD8+ T cells and adequate TNF-α production in acute HPV infection are key points for clearance. The aim of this research is to analyze the sufficiency level of retinol deposit, the expression of TNF-α, and the ratio of CD4+: CD8+ T cells in a normal cervix, clearance and persistent HPV subclinical infection, and cervical cancer group. The sufficiency level of retinol deposit was analyzed from peripheral blood using the ELISA method. The cervico-vaginal secretions, which were incubated for 24 hours, were stimulated specifically by E6 epitope HPV type-16, measuring TNF-α expression semi-quantitatively by the ELISpot method and CD4+/CD8+ T cells quantitatively by flowcytometry method. The sufficient level of retinol deposit in a normal cervix, clearance HPV subclinical infection, persistent, and cervical cancer group was 85%, 75% (OR 1.89), 33.3% (OR 11.33), and 75% (OR 1.89), respectively. The expression of TNF-α in normal cervix group was 10%, while for cervical cancer it was 75% (OR 27.00; p < 0.001). There was no expression in clearance and persistent HPV subclinical infection groups. A high ratio of CD4+: CD8+ T cells in the normal cervix and cervical cancer group was 10% and 25% (OR 0.33). There was no high ratio of CD4+: CD8+ T cells in clearance (OR 1.22) and persistent (OR 0.95) HPV subclinical infection groups. This study was able to prove that the normal cervix group has the highest retinol deposit sufficiency level and the cervical cancer group has the highest TNF-α expression (OR 27; p < 0.001). The lowest of retinol deposit sufficiency

  6. Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease.

    Science.gov (United States)

    Passos, Lívia Silva Araújo; Villani, Fernanda Nobre Amaral; Magalhães, Luísa Mourão Dias; Gollob, Kenneth J; Antonelli, Lis Ribeiro do Vale; Nunes, Maria Carmo Pereira; Dutra, Walderez Ornelas

    2016-09-15

    The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon γ (IFN-γ) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN-γ by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. Double-Negative αβ T Cells Are Early Responders to AKI and Are Found in Human Kidney.

    Science.gov (United States)

    Martina, Maria N; Noel, Sanjeev; Saxena, Ankit; Bandapalle, Samatha; Majithia, Richa; Jie, Chunfa; Arend, Lois J; Allaf, Mohamad E; Rabb, Hamid; Hamad, Abdel Rahim A

    2016-04-01

    Ischemia-reperfusion injury (IRI) is a major cause of AKI, and previous studies established important roles for conventional CD4(+) T cells, natural killer T cells, and CD4(+)CD25(+)FoxP3(+) Tregs in AKI pathogenesis. We recently identified CD4(-)CD8(-) (double-negative; DN) T cells as an important subset of αβ T cell receptor-positive cells residing in mouse kidney. However, little is known about the pathophysiologic functions of kidney DN T cells. In this study, we phenotypically and functionally characterized murine kidney DN T cells in the steady state and in response to IRI. Unlike CD4(+) and CD8(+) T cells, DN T cells in the steady state expressed high levels of CD69, CD28, and CD40L; differentially expressed IL-27 and IL-10 anti-inflammatory cytokines; spontaneously proliferated at a very high rate; and suppressed in vitro proliferation of activated CD4(+) T cells. Within the first 3-24 hours after IRI, kidney DN T cells expanded significantly and upregulated expression of IL-10. In adoptive transfer experiments, DN T cells significantly protected recipients from AKI by an IL-10-dependent mechanism. DN T cells also made up a large fraction of the T cell compartment in human kidneys. Our results indicate that DN T cells are an important subset of the resident αβ(+) T cell population in the mammalian kidney and are early responders to AKI that have anti-inflammatory properties.

  8. Double negative (DN) αβ T cells: misperception and overdue recognition.

    Science.gov (United States)

    Martina, Maria N; Noel, Sanjeev; Saxena, Ankit; Rabb, Hamid; Hamad, Abdel Rahim A

    2015-03-01

    CD4(-)CD8(-)double negative (DN) αβ T cells are legitimate components of the normal immune system. However, they are poorly understood and largely ignored by immunologists because of their historical association with the lymphoproliferation that occurs in mice (lpr and gld) and humans (autoimmune lymphoproliferative syndromes patients) with impaired Fas-mediated apoptosis where they are considered abnormal T cells. We believe that the traditional view that DN T cells that cause lymphoproliferation (hereafter referred to as lpr DN T cells) are CD4 and CD8 T cells that lost their coreceptor, conceived more than two decades ago, is flawed and that conflating lpr DN T cells with DN T cells found in normal immune system (hereafter referred to as nDN T cells) is unnecessarily dampening interest of this potentially important cell type. To begin rectifying these misperceptions, we will revisit the traditional view of lpr DN T cells and show that it does not hold true in light of recent immunological advances. In lieu of it, we offer a new model proposing that Fas-mediated apoptosis actively removes normally existing DN T cells from the periphery and that impaired Fas-mediated apoptosis leads to accumulation of these cells rather than de novo generation of DN T cells from activated CD4 or CD8 T cells. By doing so, we hope to provoke a new discussion that may lead to a consensus about the origin of lpr DN T cells and regulation of their homeostasis by the Fas pathway and reignite wider interest in nDN T cells.

  9. AECOPD外周血CD3+、CD4+、CD8+及CD16+56+细胞表达变化及胸腺五肽的干预作用%Changes of peripheral CD3+ ,CD4+ ,CD8+ and CD16+ 56+ cells in patients with acute chronic exacerbation obstructive pulmonary disease and effect of Thymopetidum intervention

    Institute of Scientific and Technical Information of China (English)

    姜克家; 潘华琴; 秦少云; 顾艺难; 陈天宇

    2014-01-01

    Objective To explore the CD3+,CD4+,CD8+ and CD16+ 56+ cells changes in patients with acute exacerbation chronic obstructive pulmonary disease(AECOPD) and effect of thymopetidum intervention.Methods Flow cytometry was used to detect the changes of CD3+,CD4+,CD8+ T cells and CD16+ 56+ natural killer (NK) cells in peripheral blood of 21 patients at acute severe stage,these patients were treated with thymopetidum and 20 normal controls.Results The levels of serum CD3+,CD4+,CD16+ 56+ levels,CD4+/CD8+ in patients with AECOPD were lower than the control group,the difference was of statistically significant (P < 0.05).After treatment,the CD3+,CD4+,CD16+ 56+,CD4+/CD8+ were increased significantly in patients with AECOPD,they are significantly different (P < 0.05).Conclusions Patients with AECOPD are of cellular immune dysfunction,thymopetidum therapy can enhance the patient's immune function.%目的 探讨慢性阻塞性肺疾病急性加重期(AECOPD)患者外周血CD3+、CD4+、CD8+及CD16+ 56+细胞的表达变化及胸腺五肽的干预作用.方法 用流式细胞术分别检测AECOPD患者21例胸腺五肽干预治疗前、后和健康人对照组20例外周血CD3+、CD4+、CD8+T细胞和CD16+ 56+ (NK)细胞的百分率,比较AECOPD患者与对照组、AECOPD患者胸腺五肽干预前、后淋巴细胞亚群的变化.结果 AECOPD患者与对照组比较,血清CD3+、CD4+、CD16+ 56+百分率、CD4+/CD8+明显降低,差异有统计学意义(P<0.05);胸腺五肽干预后与干预前比较,血清CD3+、CD4+、CD16+ 56+及CD4+/CD8+比值明显升高,差异有统计学意义(P<0.05).结论 AECOPD患者机体存在细胞免疫功能紊乱,胸腺五肽干预可提高患者免疫功能.

  10. Energy-restricted diets result in higher numbers of CD4+, CD8+, immunoglobulins (A, M, and G), and CD45RA cells in spleen and CD4+, immunoglobulin A, and CD45RA cells in colonic lamina propria of rats.

    Science.gov (United States)

    Nayak, Bob N; Friel, James K; Rempel, Curtis B; Jones, Peter J H

    2009-07-01

    Dietary energy restriction (ER) offers certain health benefits, particularly when ER is controlled through manipulation of dietary fats. Our hypothesis is that cellular immunity is modulated by dietary ER. Furthermore, we believe that the immune response may differ between spleen and colon because their lymphatic and vascular organization is different. The objective of the study was to test this hypothesis by determining the effects of dietary ER through manipulation of energy intake from high-fat (HF) diets on the expression and frequency of the CD4(+) (T-helper/T-inducer) and CD8(+) (T-cytotoxic/T-suppressor) cells, CD45RA (B-cell-specific marker), and immunoglobulins (Ig) A-, G-, and M-bearing cells in spleen and colon in rats by immunohistochemical method. Rats fed the HF diet had a significantly (P < .05) reduced number of immune cells as compared with those fed ER diets. Energy-restricted diet-fed rats showed higher (P < .05) numbers of CD4(+), CD8(+), IgA, IgM, IgG, and CD45RA cells in spleen and CD4(+), IgA, and CD45RA cells in colonic lamina propria. The IgA-containing cells were markedly higher in the colon compared with the spleen. No change occurred in the number of IgM- and IgG-containing cells in colonic tissues between groups, except for the 20% ER group where IgM-labeled cells were higher (P < .05) compared with HF and 40% ER groups. These findings suggest that ER may modulate adaptive immune function and that CD4(+) and IgA cells may serve as biological indicators for dietary energy-modulated immunoresponse in spleen and colon, respectively.

  11. MHC class II restricted innate-like double negative T cells contribute to optimal primary and secondary immunity to Leishmania major.

    Directory of Open Access Journals (Sweden)

    Zhirong Mou

    2014-09-01

    Full Text Available Although it is generally believed that CD4(+ T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3(+CD4(-CD8(- (double negative, DN T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17 and granzyme B (GrzB in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95% alpha-beta T cell receptor (αβ TCR, are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis.

  12. Multifunctional double-negative T cells in sooty mangabeys mediate T-helper functions irrespective of SIV infection.

    Directory of Open Access Journals (Sweden)

    Vasudha Sundaravaradan

    Full Text Available Studying SIV infection of natural host monkey species, such as sooty mangabeys, has provided insights into the immune changes associated with these nonprogressive infections. Mangabeys maintain immune health despite high viremia or the dramatic CD4 T cell depletion that can occur following multitropic SIV infection. Here we evaluate double-negative (DN(CD3+CD4-CD8- T cells that are resistant to SIV infection due to a lack of CD4 surface expression, for their potential to fulfill a role as helper T cells. We first determined that DN T cells are polyclonal and predominantly exhibit an effector memory phenotype (CD95+CD62L-. Microarray analysis of TCR (anti-CD3/CD28 stimulated DN T cells indicated that these cells are multifunctional and upregulate genes with marked similarity to CD4 T cells, such as immune genes associated with Th1 (IFNγ, Th2 (IL4, IL5, IL13, CD40L, Th17 (IL17, IL22 and TFH (IL21, ICOS, IL6 function, chemokines such as CXCL9 and CXCL10 and transcription factors known to be actively regulated in CD4 T cells. Multifunctional T-helper cell responses were maintained in DN T cells from uninfected and SIV infected mangabeys and persisted in mangabeys exhibiting SIV mediated CD4 loss. Interestingly, TCR stimulation of DN T cells from SIV infected mangabeys results in a decreased upregulation of IFNγ and increased IL5 and IL13 expression compared to uninfected mangabeys. Evaluation of proliferative capacity of DN T cells in vivo (BrDU labeling indicated that these cells maintain their ability to proliferate despite SIV infection, and express the homeostatic cytokine receptors CD25 (IL2 receptor and CD127 (IL7 receptor. This study identifies the potential for a CD4-negative T cell subset that is refractory to SIV infection to perform T-helper functions in mangabeys and suggests that immune therapeutics designed to increase DN T cell function during HIV infection may have beneficial effects for the host immune system.

  13. Double negative regulatory T cells in transplantation and autoimmunity: recent progress and future directions

    Institute of Scientific and Technical Information of China (English)

    Stephen C. Juvet; Li Zhang

    2012-01-01

    T lymphocytes bearing the αβ T cell receptor (TCR) but lacking CD4,CD8,and markers of natural killer (NK) cell differentiation are known as ‘double-negative’ (DN) T cells and have been described in both humans and rodent models.We and others have shown that DN T cells can act as regulatory T cells (Tregs) that are able to prevent allograft rejection,graft-versus-host disease,and autoimmune diabetes.In the last few years,new data have revealed evidence of DN Treg function in vivo in rodents and humans.Moreover,significant advances have been made in the mechanisms by which DN Tregs target antigen-specific T cells.One major limitation of the field is the lack of a specific marker that can be used to distinguish truly regulatory DN T cells (DN Tregs) from non-regulatory ones,and this is the central challenge in the coming years.Here,we review recent progress on the role of DN Tregs in transplantation and autoimmunity,and their mechanisms of action.We also provide some perspectives on how DN Tregs compare with Foxp3+ Tregs.

  14. Design of double negativity elastic metamaterial

    Directory of Open Access Journals (Sweden)

    Y.C. Su

    2015-01-01

    Full Text Available A metamaterial model that possesses simultaneously negative effective mass density and negative effective Young’s modulus is proposed in this study. Dispersion curves and dynamic responses of the model are investigated. In the double negative frequency region, it is demonstrated that the phase velocity is negative. In addition, it was found that the band gap region of the metamaterial can be predicted accurately by taking parts of single-unit cell to analyze the steady-state response. The design is also fabricated by a 3D printer.

  15. Doubled strings, negative strings and null waves

    CERN Document Server

    Blair, Chris D A

    2016-01-01

    We revisit the fundamental string (F1) solution in the doubled formalism. We show that the wave-like solution of double field theory (DFT) corresponding to the F1/pp-wave duality pair is more properly a solution of the DFT action coupled to a doubled sigma model action. The doubled string configuration which sources the pp-wave can be thought of as static gauge with the string oriented in a dual direction. We also discuss the DFT solution corresponding to a vibrating string, carrying both winding and momentum. We further show that the solution dual to the F1 in both time and space can be viewed as a "negative string" solution. Negative branes are closely connected to certain exotic string theories which involve unusual signatures for both spacetime and brane worldvolumes. In order to better understand this from the doubled point of view, we construct a variant of DFT suitable for describing theories in which the fundamental string has a Euclidean worldsheet, for which T-dualities appear to change the spacetim...

  16. Doubled strings, negative strings and null waves

    Energy Technology Data Exchange (ETDEWEB)

    Blair, Chris D.A. [Theoretische Natuurkunde, Vrije Universiteit Brussel, and the International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium)

    2016-11-08

    We revisit the fundamental string (F1) solution in the doubled formalism. We show that the wave-like solution of double field theory (DFT) corresponding to the F1/pp-wave duality pair is more properly a solution of the DFT action coupled to a doubled sigma model action. The doubled string configuration which sources the pp-wave can be thought of as static gauge with the string oriented in a dual direction. We also discuss the DFT solution corresponding to a vibrating string, carrying both winding and momentum. We further show that the solution dual to the F1 in both time and space can be viewed as a “negative string” solution. Negative branes are closely connected to certain exotic string theories which involve unusual signatures for both spacetime and brane worldvolumes. In order to better understand this from the doubled point of view, we construct a variant of DFT suitable for describing theories in which the fundamental string has a Euclidean worldsheet, for which T-dualities appear to change the spacetime signature.

  17. Double negative metamaterials based on ferromagnetic microwires

    Science.gov (United States)

    Carbonell, Jorge; García-Miquel, Héctor; Sánchez-Dehesa, José

    2010-01-01

    Ferromagnetic microwires are investigated as fundamental components to generate metamaterials with double negative parameters. Electric and magnetic responses are, respectively, based on the finite conductivity and ferromagnetic resonance of the wires that in turn depend on their chemical composition. Tuning properties of samples are investigated in terms of the composition of the alloy and the applied magnetic field. The samples are measured and simulated in a waveguide environment for a large microwave frequency range. Numerical modeling supports the experimental results and helps to understand the physics involved in the transmission phenomena. Radius and conductivity of the wires are pointed out as the most critical parameters to generate a double negative response in terms of permittivity and permeability.

  18. Double Negative Metamaterials in Dielectric Waveguide Configurations

    OpenAIRE

    Clark, Jeffrey

    2006-01-01

    With the recent resurgence of interest in double negative (DNG) materials and the reported construction of a metamaterial with DNG characteristics, applications of these materials become feasible and examination of the behavior of systems and devices a potentially fruitful topic. The most promising area of research, upon inquiry into past work related to DNG materials, proves to be dielectric waveguides. The present investigation, then, focuses on the inclusion of DNG materials in various ...

  19. Bim-mediated apoptosis is not necessary for thymic negative selection to ubiquitous self-antigens.

    Science.gov (United States)

    Hu, Qian; Sader, Alyssa; Parkman, Julia C; Baldwin, Troy A

    2009-12-15

    T cell education in the thymus is critical for establishing a functional, yet self-tolerant, T cell repertoire. Negative selection is a key process in enforcing self-tolerance. There are many questions that surround the mechanism of negative selection, but it is currently held that apoptosis initiated by Bim and/or Nur77 is critical for negative selection. Recent studies, however, have questioned the necessity of Bim in maintaining both central and peripheral T cell tolerance. To reconcile these apparently contradictory findings, we examined the role of Bim in negative selection in the well-characterized, physiological HY(cd4) mouse model. We found that while Bim expression was required for CD4(+)CD8(+) double-positive thymocyte apoptosis, it was not required for negative selection. Furthermore, Bim deficiency did not alter the frequency or affinity of male reactive cells that escape negative selection in an oligoclonal repertoire. Collectively, these studies indicate that negative selection occurs efficiently in the absence of apoptosis and suggest that the current paradigm of negative selection requiring apoptosis be revisited.

  20. On extending the concept of double negativity to acoustic waves

    Institute of Scientific and Technical Information of China (English)

    CHAN C.T.; LI Jensen; FUNG K.H.

    2006-01-01

    The realization of double negative electromagnetic wave media, sometimes called left-handed materials (LHMs) or metamaterials, have drawn considerable attention in the past few years. We will examine the possibility of extending the concept to acoustic waves. We will see that acoustic metamaterials require both the effective density and bulk modulus to be simultaneously negative in the sense of an effective medium. If we can find a double negative (negative density and bulk modulus) acoustic medium, it will be an acoustic analogue of Veselago's medium in electromagnetism, and share many novel consequences such as negative refractive index and backward wave characteristics. We will give one example of such a medium.

  1. Double Negative Materials (DNM), Phenomena and Applications

    Science.gov (United States)

    2009-07-01

    9 Feynman , R. P., R. B. Leighton, and M. Sands. Quantum physics . Vol. 1 of The Feynman Lectures on Physics (Addison-Wesley, 1964...involved in justifying basic physical questions of causality, validity of the concept of negative index of refraction interpretation of experimental...Materials ......................................... 2-4 3. Basic Physics Phenomena

  2. Single-resonator double-negative metamaterial

    Energy Technology Data Exchange (ETDEWEB)

    Warne, Larry K.; Basilio, Lorena I.; Langston, William L.; Johnson, William A.; Ihlefeld, Jon; Ginn, III, James C.; Clem, Paul G.; Sinclair, Michael B.

    2016-06-21

    Resonances can be tuned in dielectric resonators in order to construct single-resonator, negative-index metamaterials. For example, high-contrast inclusions in the form of metallic dipoles can be used to shift the first electric resonance down (in frequency) to the first magnetic resonance, or alternatively, air splits can be used to shift the first magnetic resonance up (in frequency) near the first electric resonance. Degenerate dielectric designs become especially useful in infrared- or visible-frequency applications where the resonator sizes associated with the lack of high-permittivity materials can become of sufficient size to enable propagation of higher-order lattice modes in the resulting medium.

  3. Single-resonator double-negative metamaterial

    Science.gov (United States)

    Warne, Larry K.; Basilio, Lorena I.; Langston, William L.; Johnson, William A.; Ihlefeld, Jon; Ginn, III, James C.; Clem, Paul G.; Sinclair, Michael B.

    2016-06-21

    Resonances can be tuned in dielectric resonators in order to construct single-resonator, negative-index metamaterials. For example, high-contrast inclusions in the form of metallic dipoles can be used to shift the first electric resonance down (in frequency) to the first magnetic resonance, or alternatively, air splits can be used to shift the first magnetic resonance up (in frequency) near the first electric resonance. Degenerate dielectric designs become especially useful in infrared- or visible-frequency applications where the resonator sizes associated with the lack of high-permittivity materials can become of sufficient size to enable propagation of higher-order lattice modes in the resulting medium.

  4. Viscothermal Losses in Double-Negative Acoustic Metamaterials

    DEFF Research Database (Denmark)

    Cutanda Henriquez, Vicente; García-Chocano, Victor M.; Sánchez-Dehesa, José

    2017-01-01

    The influence of losses in double-negative metamaterial slabs recently introduced by Graciá-Salgado et al. [Phys. Rev. B 88, 224305 (2013)] is comprehensively studied. Viscous and thermal losses are considered in the linearized Navier-Stokes equations with no flow. Despite the extremely low...

  5. Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis

    DEFF Research Database (Denmark)

    Solti, Izabella; Kvell, Krisztian; Talaber, Gergely;

    2015-01-01

    Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first...... mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3...... involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone's deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes....

  6. Space-coiling metamaterials with double negativity and conical dispersion.

    Science.gov (United States)

    Liang, Zixian; Feng, Tianhua; Lok, Shukin; Liu, Fu; Ng, Kung Bo; Chan, Chi Hou; Wang, Jinjin; Han, Seunghoon; Lee, Sangyoon; Li, Jensen

    2013-01-01

    Metamaterials are effectively homogeneous materials that display extraordinary dispersion. Negative index metamaterials, zero index metamaterials and extremely anisotropic metamaterials are just a few examples. Instead of using locally resonating elements that may cause undesirable absorption, there are huge efforts to seek alternative routes to obtain these unusual properties. Here, we demonstrate an alternative approach for constructing metamaterials with extreme dispersion by simply coiling up space with curled channels. Such a geometric approach also has an advantage that the ratio between the wavelength and the lattice constant in achieving a negative or zero index can be changed in principle. It allows us to construct for the first time an acoustic metamaterial with conical dispersion, leading to a clear demonstration of negative refraction from an acoustic metamaterial with airborne sound. We also design and realize a double-negative metamaterial for microwaves under the same principle.

  7. A Rectangular Split Ring Double Negative Metamaterial having Simultaneous Negative Permittivity and Permeability

    Directory of Open Access Journals (Sweden)

    Muhammad Waqas

    2014-06-01

    Full Text Available The scope of this paper is to design and simulate a novel structure having simultaneous negative permittivity and permeability so called double negative metamaterial or left handed material. The DNG structure consists of five rectangular split ring resonators on one side of dielectric medium and a couple of wires on other side. The complex permittivity, permeability and refractive index are determined from simulated Scattering parameters using direct retrieval method. Simulations of DNG structure are carried out using CST MWS. MATLAB is used for verification of negative values of structure's parameter.

  8. Comparative Analysis of Guided Modal Properties of Double-Positive and Double-Negative Metamaterial Slab Waveguides

    Directory of Open Access Journals (Sweden)

    K. Y. Kim

    2009-06-01

    Full Text Available The guided modal properties of double-positive and double-negative metamaterial slab waveguides are numerically analyzed and compared when varying the dielectric and magnetic constants. As the cutoff frequencies of both slab waveguides remained unchanged when the absolute value of the refractive index was kept invariant, this enabled an effective comparison of the respective guided modes. Thus, the guided mode dispersion characteristics of the double-positive and double-negative slab waveguides were analyzed and compared, including several higher order modes. As a result, this comparative analysis provides greater physical insights and a better understanding of the guided modal characteristics of double-negative metamaterial slab waveguides.

  9. Investigation of gain enhancement of electrically small antennas using double-negative, single-negative, and double-positive materials.

    Science.gov (United States)

    Ghosh, B; Ghosh, S; Kakade, A B

    2008-08-01

    In this paper, it is shown that a double-negative or a mu-negative shell can be used to achieve a very high gain for an electrically small loop. It is also seen that together with the high gain, the metamaterial shell can be used to achieve a very uniform gain characteristic with respect to the shell dimensions. This is accomplished by a proper choice of the media parameters of the metamaterial shell and the region surrounding the antenna. This significantly eases the fabrication constraints and the close tolerances on the shell which was a major drawback towards the practical realization of the shell. Also, significant power gain can be obtained when the radiated power from the metamaterial shell is compared to the power radiated by a loop of the same radius as the outer radius of the shell. In addition, it is also found that a double-positive shell of the same dimensions as the metamaterial shell can be used to significantly increase the gain of the infinitesimal antenna. The power gain characteristics show distinct resonant peaks in this case. Excellent matching characteristics are observed corresponding to the radiated power gain.

  10. Influencing factor of gram negative bacteria for adult patients with community-acquired pneumonia%社区获得性肺炎革兰氏阴性菌感染的影响因素

    Institute of Scientific and Technical Information of China (English)

    边喜明

    2016-01-01

    目的:探讨社区获得性肺炎( CAP)成年患者革兰氏阴性细菌感染的影响因素。方法选取确诊为社区获得性肺炎的成人患者186例。采集患者痰标本检测致病菌;对患者一般资料进行统计分析。结果186例CAP患者中,60例患者检测出92株细菌,占32.26%;其中革兰氏阳性菌19株(14例),革兰氏阴性菌73株(46例),分别占20.65%和79.35%。46革兰氏阴性菌CAP患者与186例CAP患者在年龄、入院前应用抗生素、合并基础疾病、白细胞异常、中性粒细胞、营养不良、总胆红素、CD4+和CD4+/CD8+比值存在显著性差异(P<0.05或P<0.01)。分析显示,入院前应用抗生素、合并基础疾病、白细胞异常、中性粒细胞、营养不良、总胆红素和CD4+/CD8+比值为CAP成年患者革兰氏阴性细菌感染的独立影响因素( P<0.05或P<0.01)。结论入院前应用抗生素、合并基础疾病、白细胞异常、中性粒细胞、营养不良、总胆红素和 CD4+/CD8+比值为CAP成年患者革兰氏阴性细菌感染的独立影响因素。%Objective To investigate the influencing factor of gram negative bacteria for adult patients with community-acquired pneumonia. Methods 186 adult patients with community acquired pneumonia were selected. The sputum samples were detected for pathogenic bacterium, and their general data were analyzed. Results Among 60 patients, 92 strains were detected, accounting for 32. 26%. There were 19 strains of gram positive strains (14 ca-ses) and 73 strains of gram negative strains (46 cases), accounting for 20. 65% and 79. 35%, respectively. There were significant differences in age, antibiotics use before admission, underlying disease, leukocyte disorder, neutro-phile granulocyte, malnutrition, total bilirubin, CD4+ and CD4+ /CD8+ between gram negative strains infected commu-nity acquired pneumonia and total community acquired pneumonia ( P <0. 05 or P <0. 01 ) . Logistic regression showed that

  11. Double-negative metamaterial research for accelerator applications

    Energy Technology Data Exchange (ETDEWEB)

    Antipov, S. [Department of Biological, Chemical, and Physical Sciences, Illinois Institute of Technology, Chicago, IL 60616 (United States); Spentzouris, L. [Department of Biological, Chemical, and Physical Sciences, Illinois Institute of Technology, Chicago, IL 60616 (United States)], E-mail: spentzouris@iit.edu; Gai, W.; Liu, W.; Power, J.G. [Argonne National Laboratory, Argonne, IL 60439 (United States)

    2007-09-11

    Material properties are central to the design of particle accelerators. One area of advanced accelerator research is to investigate novel materials and structures and their potential use in extending capabilities of accelerator components. Within the past decade a new type of artificially constructed material having the unique property of simultaneously negative permittivity and permeability has been realized, and is under intense investigation, primarily by the optical physics and microwave engineering communities [C.M. Soukoulis, Science 315 (2007) 47; D.R. Smith, J.B. Pendry, M.C.K. Wiltshire, Science 305 (2004) 788; J.B. Pendry, A.J. Holden, W.J. Stewart, I. Youngs, Phys. Rev. Lett. 76 (1996) 4773]. Although they are typically constructed of arrays of discrete cells, as long as the condition that the wavelength of applied radiation is significantly greater than the cell dimensions is met, the material mimics a continuous medium and can be described with the bulk properties of permittivity, {epsilon}, and permeability, {mu}. When the permittivity and permeability are simultaneously negative in some frequency range, the metamaterial is called double negative (DNM) or left-handed (LHM) and has unusual properties, such as a negative index of refraction. An investigation of these materials in the context of accelerators is being carried out by IIT and the Argonne Wakefield Accelerator Facility [S. Antipov, W. Liu, W. Gai, J. Power, L. Spentzouris, AIP Conf. Proc. 877 (2006); S. Antipov, W. Liu, J. Power, L. Spentzouris, Design, Fabrication, and Testing of Left-Handed Metamaterial, Wakefield Notes at Argonne Wakefield Accelerator, < (http://www.hep.anl.gov/awa/wfnotes/wf229.pdf)>]. Waveguides loaded with metamaterials are of interest because the DNM can change the dispersion relation of the waveguide significantly. For example, slow backward waves can be produced in a DNM-loaded waveguide without having corrugations. This article begins with a brief introduction of

  12. Double-negative metamaterial research for accelerator applications

    Science.gov (United States)

    Antipov, S.; Spentzouris, L.; Gai, W.; Liu, W.; Power, J. G.

    2007-09-01

    Material properties are central to the design of particle accelerators. One area of advanced accelerator research is to investigate novel materials and structures and their potential use in extending capabilities of accelerator components. Within the past decade a new type of artificially constructed material having the unique property of simultaneously negative permittivity and permeability has been realized, and is under intense investigation, primarily by the optical physics and microwave engineering communities [C.M. Soukoulis, Science 315 (2007) 47; D.R. Smith, J.B. Pendry, M.C.K. Wiltshire, Science 305 (2004) 788; J.B. Pendry, A.J. Holden, W.J. Stewart, I. Youngs, Phys. Rev. Lett. 76 (1996) 4773]. Although they are typically constructed of arrays of discrete cells, as long as the condition that the wavelength of applied radiation is significantly greater than the cell dimensions is met, the material mimics a continuous medium and can be described with the bulk properties of permittivity, ɛ, and permeability, μ. When the permittivity and permeability are simultaneously negative in some frequency range, the metamaterial is called double negative (DNM) or left-handed (LHM) and has unusual properties, such as a negative index of refraction. An investigation of these materials in the context of accelerators is being carried out by IIT and the Argonne Wakefield Accelerator Facility [S. Antipov, W. Liu, W. Gai, J. Power, L. Spentzouris, AIP Conf. Proc. 877 (2006); S. Antipov, W. Liu, J. Power, L. Spentzouris, Design, Fabrication, and Testing of Left-Handed Metamaterial, Wakefield Notes at Argonne Wakefield Accelerator, ]. Waveguides loaded with metamaterials are of interest because the DNM can change the dispersion relation of the waveguide significantly. For example, slow backward waves can be produced in a DNM-loaded waveguide without having corrugations. This article begins with a brief introduction of known design principles for realizing a DNM [J.B. Pendry, A

  13. Co-receptor choice by V alpha14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection.

    Science.gov (United States)

    Engel, Isaac; Hammond, Kirsten; Sullivan, Barbara A; He, Xi; Taniuchi, Ichiro; Kappes, Dietmar; Kronenberg, Mitchell

    2010-05-10

    Mouse natural killer T (NKT) cells with an invariant V alpha14-J alpha18 rearrangement (V alpha14 invariant [V alpha14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krüppel family (Th-POK) is expressed by V alpha14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha14i NKT cells.

  14. FoxM1, a forkhead transcription factor is a master cell cycle regulator for mouse mature T cells but not double positive thymocytes.

    Directory of Open Access Journals (Sweden)

    Ling Xue

    Full Text Available FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating cells but is surprisingly also found in non-proliferating CD4(+CD8(+ double positive thymocytes. Here, we addressed the role of FoxM1 in T cell development by generating and analyzing two different lines of T-cell specific FoxM1 deficient mice. As expected, FoxM1 is required for proliferation of early thymocytes and activated mature T cells. Defective expression of many cell cycle proteins was detected, including cyclin A, cyclin B1, cdc2, cdk2, p27 and the Rb family members p107 and p130 but surprisingly not survivin. Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4(+CD8(+ thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation. Thus, regulation of cell cycle genes by FoxM1 is stage- and context-dependent.

  15. Effect of the serotonin receptor agonist, buspirone, on immune function in HIV-infected individuals: a six-month randomized, double-blind, placebo-controlled trial

    DEFF Research Database (Denmark)

    Eugen-Olsen, Jesper; Benfield, T; Axen, T E;

    2000-01-01

    . Blood samples were drawn prior to treatment, after 1 week, 1 month, 3 months, and 6 months, and as a follow-up sample 1 month after completion of study. RESULTS: A significant decrease in CD8+ T-cell counts (p =.02) and an increase in CD4/CD8 ratio (p =.0003) in buspirone-treated patients compared......PURPOSE: Previous studies have shown that agents modulating the cAMP/PKA pathway have a beneficial effect on immune reconstitution in HIV-infected individuals. Here we evaluate the effect of buspirone on immune function as measured by CD4 and CD8 T-cell counts, CD4/CD8 T-cell ratio, HIV viral load......, and response to pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals. METHOD: Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per microL were enrolled in a 6-month double-blinded placebo controlled trial. No patients received antiretroviral therapy during the study...

  16. Autoimmune lymphoproliferative syndrome (ALPS): a rare cause of immune cytopenia.

    Science.gov (United States)

    John, M Joseph; Rajasekhar, Reena; Mathews, Vikram

    2008-02-01

    Autoimmune Lymphoproliferative syndrome (ALPS) is an inherited disorder manifesting with autoimmune cytopenia, lymphadenopathy and splenomegaly. The differential diagnosis includes infections, autoimmune disorders or malignancies. The disease is characterized by accumulation of double negative (CD3+ CD4- CD8-) T cells (DNT) in the peripheral blood. We describe a case and review the literature.

  17. Double Negativity in 3D Space Coiling Metamaterials

    Science.gov (United States)

    Maurya, Santosh K.; Pandey, Abhishek; Shukla, Shobha; Saxena, Sumit

    2016-09-01

    Metamaterials displaying negative refractive index has remarkable potential to facilitate the manipulation of incident waves for wide variety of applications such as cloaking, superlensing and the like. Space-coiling approach is a recently explored technique to achieve extreme properties. The space coiling phenomena cause less energy absorption as compared to local resonating phenomena for obtaining extreme parameters. Here we show extreme properties in doubly negative 3D space coiling acoustic metamaterials. Frequency dispersive spectrum of extreme constitutive parameters has been calculated for 2D maze and 3D space coiling labyrinthine structure. This is in good agreement to the calculated acoustic band dispersion.

  18. Double Negativity in 3D Space Coiling Metamaterials.

    Science.gov (United States)

    Maurya, Santosh K; Pandey, Abhishek; Shukla, Shobha; Saxena, Sumit

    2016-09-21

    Metamaterials displaying negative refractive index has remarkable potential to facilitate the manipulation of incident waves for wide variety of applications such as cloaking, superlensing and the like. Space-coiling approach is a recently explored technique to achieve extreme properties. The space coiling phenomena cause less energy absorption as compared to local resonating phenomena for obtaining extreme parameters. Here we show extreme properties in doubly negative 3D space coiling acoustic metamaterials. Frequency dispersive spectrum of extreme constitutive parameters has been calculated for 2D maze and 3D space coiling labyrinthine structure. This is in good agreement to the calculated acoustic band dispersion.

  19. Effect of a Perioperative Nutritional Supplementation with Oral Impact® in Patients undergoing Hepatic Surgery for Liver Cancer: A Prospective, Placebo-Controlled, Randomized, Double-Blind Study.

    Science.gov (United States)

    Seguin, Philippe; Locher, Clara; Boudjema, Karim; Hamon, Catherine; Mouchel, Catherine; Malledant, Yannick; Bellissant, Eric

    2016-01-01

    Perioperative nutrition with supplements containing L-arginine, ω3-polyunsaturated fatty acids, and nucleotides could boost liver function recovery, immune response, and resistance to infection after hepatic resection. We conducted a placebo-controlled, randomized, double-blind study to assess the effect of a perioperative nutritional supplementation with Oral Impact® in patients undergoing hepatic surgery for liver cancer. Treatment was given three times daily for 7 days before and 3 days after surgery. Primary outcome was factor V, 3 days after surgery. Thirty-five patients (placebo: 17; Oral Impact: 18) were included. Five patients (placebo: three; Oral Impact: two) were not operated and five (placebo: two; Oral Impact: three) did not undergo hepatic resection. Factor V (mean ± SD) was 70 ± 27% and 79 ± 25% (P = 0.409) 3 days after surgery and 90 ± 30% and 106 ± 16% (P = 0.066) 5 days after surgery, in placebo and Oral Impact groups, respectively. There were no significant differences between groups on other outcomes assessing liver function recovery (bile production, γ-glutamyl transferase, α-fetoprotein), immune response (CD3, CD4, CD8 cells, CD4/CD8 ratio, natural killer cells, B lymphocytes), number of infections, and tolerance. A 10-day perioperative nutritional supplementation with Oral Impact does not improve hepatic function, immune response, and resistance to infection in patients undergoing hepatic surgery for liver cancer.

  20. Hit Twice? Danish Evidence on the Double-Negative Effect on the Earnings of Immigrant Women

    DEFF Research Database (Denmark)

    Nielsen, Helena Skyt; Rosholm, Michael; Smith, Nina;

    2000-01-01

    In this paper, we investigate whether there is a double-negative effect on the wages of immigrant women in Denmark stemming from a negative effect from both gender and foreign country of origin. We estimate separate wage equations for Danes and a number of immigrant groups correcting for sample s...... selection and individual specific effects. Based on a Danish panel of register data, we find that all women are affected by a substantial gender discrimination in wages, but only Pakistani women experience a double-negative effect.......In this paper, we investigate whether there is a double-negative effect on the wages of immigrant women in Denmark stemming from a negative effect from both gender and foreign country of origin. We estimate separate wage equations for Danes and a number of immigrant groups correcting for sample...

  1. Numerical models of single- and double-negative metamaterials including viscous and thermal losses

    DEFF Research Database (Denmark)

    Cutanda Henriquez, Vicente; Sánchez-Dehesa, José

    2017-01-01

    Negative index acoustic metamaterials are artificial structures made of subwavelength units arranged in a lattice, whose effective acoustic parameters, bulk modulus and mass density, can be negative. In these materials, sound waves propagate inside the periodic structure, assumed rigid, showing...... extraordinary properties. We are interested in two particular cases: a double-negative metamaterial, where both parameters are negative at some frequencies, and a single-negative metamaterial with negative bulk modulus within a broader frequency band. In previous research involving the double......-negative metamaterial, numerical models with viscous and thermal losses were used to explain that the extraordinary behavior, predicted by analytical models and numerical simulations with no losses, disappeared when the metamaterial was measured in physical setups. The improvement of the models is allowing now a more...

  2. A Double-Negative Effect on the Earnings of Immigrant Women? Evidence from Denmark

    DEFF Research Database (Denmark)

    Nielsen, Helena Skyt; Husted, L.; Rosholm, Michael

    In this paper we investigate whether there exists a double-negative effect on the earnings of immigrant women in Denmark stemming from a combined negative effect of gender and foreign country of origin. We estimate separate wage equations for Danes and a number of immigrant groups allowing...... for individual specific effects. Considering females, correcting for possible sample selection bias due to the participation decision is essential. Based on a Danish panel of register data, we identify some groups of immigrant females that experience a strong and persistent double-negative effect on wages even...

  3. Hit Twice? Danish Evidence on the Double-Negative Effect on the Earnings of Immigrant Women

    DEFF Research Database (Denmark)

    Nielsen, Helena Skyt; Rosholm, Michael; Smith, Nina

    2000-01-01

    In this paper, we investigate whether there is a double-negative effect on the wages of immigrant women in Denmark stemming from a negative effect from both gender and foreign country of origin. We estimate separate wage equations for Danes and a number of immigrant groups correcting for sample...... selection and individual specific effects. Based on a Danish panel of register data, we find that all women are affected by a substantial gender discrimination in wages, but only Pakistani women experience a double-negative effect....

  4. Hit Twice? Danish Evidence on the Double-Negative Effect on the Earnings of Immigrant Women

    DEFF Research Database (Denmark)

    Nielsen, Helena Skyt; Rosholm, Michael; Smith, Nina

    In this paper, we investigate whether there is a double-negative effect on the wages of immigrant women in Denmark stemming from a negative effect from both gender and foreign country of origin. We estimate separate wage equations for Danes and a number of immigrant groups correcting for sample...... selection and individual specific effects. Based on a Danish panel of register data, we find that all women are affected by a substantial gender discrimination in wages, but only Pakistani women experience a double-negative effect....

  5. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast

    Directory of Open Access Journals (Sweden)

    Ankita Singh Rathore

    2014-01-01

    Full Text Available Background & objectives: Tumour infiltrating lymphocytes (TILs represent the host immune response against cancer cells associated with good or bad prognosis in different tumour types. This study was undertaken to evaluate the significance of CD3+, CD4+ and CD8+ TILs in breast cancer tissues in relation to clinico-pathological variables and survival outcome. Methods: Immunohistochemistry (IHC was performed with antibodies against CD3, CD4 and CD8 antigens on formalin-fixed paraffin-embedded tissue sections of 150 breast cancer patients. Intratumoural and stromal TIL counting was performed semiquantitatively. Results: The higher CD3+, CD4+ and CD8+ intratumoural and stromal counts showed independent and direct association with good prognosis. The prognostic predictor value of intratumoural counts was higher than stromal counts. The independent associations of intratumoural and stromal counts became more prominent when adjusted with stage and grade, respectively. Among intratumoural counts, the high (++/+++ CD4+ count (OR=3.85, 95% CI=3.28-16.71, P<0.001 showed the highest survival followed by CD3+ (OR=2.70, 95% CI=1.76-8.30, P=0.001 and CD8+ (OR=2.58, 95% CI=1.55-5.86, p0 =0.001 the least when compared to respective low (+ counts. In contrast, among stromal counts, the high CD8+ count (OR=3.13, 95% CI=2.20-9.57, p0 <0.001 showed the highest survival followed by CD4+ (OR=3.02, 95% CI=2.07-8.89, p0 <0.001 and CD3+ (OR=2.45, 95% CI=1.53-6.73, p0 =0.002 the least. Interpretation & conclusions: Our results suggest that intratumoural CD4+ and stromal CD8+ counts by immunohistochemistry may serve as an independent prognosticator for favourable outcome in breast cancer.

  6. Effects of concurrent training on inflammatory markers and expression of CD4, CD8, and HLA-DR in overweight and obese adults

    Directory of Open Access Journals (Sweden)

    Alana Colato

    2014-12-01

    Full Text Available The number of people who are overweight or obese is increasing worldwide and the quality of life of these people can be affected by their condition. Physical training has been studied in obese patients and is correlated with low-grade inflammation and alterations in the immune system. This study investigated the effect of concurrent training on anthropometric, inflammatory, and immunological parameters in overweight and obese adults. Fourteen sedentary volunteers (men and women with a body mass index between 25 kg/m2 and 39.9 kg/m2 from Porto Alegre, Brazil attended a 12-week course of concurrent training. We analyzed: prior to and after training, anthropometric parameters, cytokine serum levels (interleukin 6, tumor necrosis factor α, interferon γ, interleukin 17A and interleukin 10; measured by enzyme-linked immunosorbent assay, high-sensitive C reactive protein (measured by turbidimetry, and the frequency of T lymphocytes and monocytes (CD3+CD4+, CD3+CD8+, and HLA-DR+ in peripheral blood (measured by flow cytometry. The sample consisted of ten women and four men with a mean ± SD age of 47.58 ± 3.01 years. After 12 weeks of training we observed a reduction in body weight, body mass index, waist, abdomen, and hip circumferences, the percentage mass of fat, and an increase in the time taken to reach exhaustion (p < 0.05. The participants had increased frequencies of CD3+CD4+ and CD3+CD8+ T lymphocytes and a reduction in the frequencies of HLA-DR+ monocytes (p < 0.05. Interestingly, the levels of tumor necrosis factor α and high-sensitive C reactive protein increased (p < 0.05. Our data suggest that concurrent training can improve body composition as well as increasing T cell proliferation in overweight and obese patients. However, the progression of the exercises can be physiologically stressful to these patients, as demonstrated by the inflammatory markers.

  7. Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats.

    Science.gov (United States)

    Webb, Craig B; Lehman, Tracy L; McCord, Kelly W

    2008-10-01

    This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (> or =16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66-0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.

  8. Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection

    DEFF Research Database (Denmark)

    Buggert, Marcus; Frederiksen, Juliet Wairimu; Noyan, Kajsa;

    2014-01-01

    HIV disease progression is characterized by numerous pathological changes of the cellular immune system. Still, the CD4 cell count and viral load represent the laboratory parameters that are most commonly used in the clinic to determine the disease progression. In this study, we conducted an inte...

  9. Low CD4/CD8 T-cell ratio associated with inflammatory arthropathy in human T-cell leukemia virus type I Tax transgenic mice.

    Directory of Open Access Journals (Sweden)

    Takeo Ohsugi

    Full Text Available BACKGROUND: Human T-cell leukemia virus type I (HTLV-1 can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. A transgenic mouse that expresses HTLV-1 Tax also develops T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. The aim of this study was to identify the primary T-cell subsets involved in the development of arthropathy in Tax transgenic mice. PRINCIPAL FINDINGS: By 24 months of age, Tax transgenic mice developed severe arthropathy with a cumulative incidence of 22.8%. The pathological findings of arthropathy in Tax transgenic mice were similar to those seen in human rheumatoid arthritis or mouse models of rheumatoid arthritis, with synovial proliferation and a positive rheumatoid factor. Before the onset of spontaneous arthropathy, young and old Tax transgenic mice were not sensitive to collagen and did not develop arthritis after immunization with type II collagen. The arthropathic Tax transgenic mice showed a significantly decreased proportion of splenic CD4(+ T cells, whereas the proportion of splenic CD8(+ T cells was increased. Regulatory T cells (CD4(+CD25(+Foxp3(+ were significantly decreased and CD8(+ T cells that expressed the chemokine receptor CCR4 (CD8(+CCR4(+ were significantly increased in arthropathic Tax transgenic mice. The expression of tax mRNA was strong in the spleen and joints of arthropathic mice, with a 40-fold increase compared with healthy transgenic mice. CONCLUSIONS: Our findings reveal that Tax transgenic mice develop rheumatoid-like arthritis with proliferating synovial cells in the joints; however, the proportion of different splenic T-cell subsets in these mice was completely different from other commonly used animal models of rheumatoid arthritis. The crucial T-cell subsets in arthropathic Tax transgenic mice appear to resemble those in HAM/TSP patients rather than those in rheumatoid arthritis patients.

  10. Theory of negative-refractive-index response of double-fishnet structures.

    Science.gov (United States)

    Mary, A; Rodrigo, Sergio G; Garcia-Vidal, F J; Martin-Moreno, L

    2008-09-05

    A theory is presented of the negative refractive index observed in the so-called double-fishnet structures. We find that the electrical response of these structures is dominated by the cutoff frequency of the hole waveguide whereas the resonant magnetic response is due to the excitation of gap surface plasmon polaritons propagating along the dielectric slab. Associated with this origin, we show how the negative refractive index in these metamaterials presents strong dispersion with the parallel momentum of the incident light.

  11. Transmission properties of one-dimensional Photonic crystals containing double-negative and single-negative materials

    Institute of Scientific and Technical Information of China (English)

    Xia Li; Kang Xie; Haiming Jiang

    2008-01-01

    The transmission properties of one-dimensional photonic crystals containing double-negative and singlenegative materials are studied theoretically.A special kind of photonic band gap is found in this structure.This gap is invariant with scaling and insensitive to thickness fluctuation.But when changing the ratio of the thickness of two media.the width of the gap could be enlarged.The defect modes are analyzed by inducing a linear defect layer in the structure.It is found that the number of defect modes will increase when the thickness of the defect layer becomes larger.

  12. Creating double negative index materials using the Babinet principle with one metasurface

    Science.gov (United States)

    Zhang, Lei; Koschny, Thomas; Soukoulis, C. M.

    2013-01-01

    Metamaterials are patterned metallic structures which permit access to a novel electromagnetic response, negative index of refraction, impossible to achieve with naturally occurring materials. Using the Babinet principle, the complementary split ring resonator (SRR) is etched in a metallic plate to provide negative ɛ, with perpendicular direction. Here we propose a new design, etched in a metallic plate to provide negative magnetic permeability μ, with perpendicular direction. The combined electromagnetic response of this planar metamaterial, where the negative μ comes from the aperture and the negative ɛ from the remainder of the continuous metallic plate, allows achievement of a double negative index metamaterial (NIM) with only one metasurface and strong transmission. These designs can be used to fabricate NIMs at microwave and optical wavelengths and three-dimensional metamaterials.

  13. Double-negative acoustic metamaterial based on hollow steel tube meta-atom

    CERN Document Server

    Chen, Huaijun; Ding, Changlin; Luo, Chunrong; Zhao, Xiaopeng

    2012-01-01

    We presented an acoustic 'meta-atom' model of hollow steel tube (HST). The simulated and experimental results demonstrated that the resonant frequency is closely related to the length of the HST. Based on the HST model, we fabricated a two-dimensional (2D) acoustic metamaterial (AM) with negative effective mass density, which put up the transmission dip and accompanied inverse phase in experiment. By coupling the HST with split hollow sphere (SHS), another kind of 'meta-atom' with negative effective modulus in the layered sponge matrix, a three-dimensional (3D) AM was fabricated with simultaneously negative modulus and negative mass density. From the experiment, it is shown that the transmission peak similar to the electromagnetic metamaterials exhibited in the double-negative region of the AM. We also demonstrated that this kind of doble-negative AM can faithfully distinguish the acoustic sub-wavelength details ({\\lambda}/7) at the resonance frequency of 1630Hz.

  14. The Problems of the Mental Logic with the Double Negation: The Necessity of a Semantic Approach

    Directory of Open Access Journals (Sweden)

    López-Astorga Miguel

    2016-09-01

    Full Text Available The double negation has always been considered by the logical systems from ancient times to the present. In fact, that is an issue that the current syntactic theories studying human reasoning, for example, the mental logic theory, address today. However, in this paper, I claim that, in the case of some languages such as Spanish, the double negation causes problems for the cognitive theories mainly based on formal schemata and supporting the idea of a universal syntax of thought in the human mind. Thus, I propose that, given those problems, semantic frameworks such as that of the mental models theory seem to be more appropriate for explaining the human inferential activity.

  15. Negative and positive hysteresis in double-cavity optical bistability in three-level atom

    CERN Document Server

    Babu, H Aswath

    2010-01-01

    We present novel hysteretic behaviour of a three-level ladder atomic system exhibiting double-cavity optical bistability in the mean-field limit. The two fields coupling the atomic system experience feedback via two independent, unidirectional, single mode ring cavities and exhibit cooperative phenomena, simultaneously. The system displays a range of rich dynamical features varying from normal switching to self pulsing and a period-doubling route to chaos for both the fields. We focus our attention to a new hump like feature in the bistable curve arising purely due to cavity induced inversion, which eventually leads to negative hysteresis in the bistable response. This is probably the only all-optical bistable system that exhibits positive as well as negative bistable hysteresis in different input field intensity regimes. For both the fields, the switching times, the associated critical slowing down, the self-pulsing characteristics, and the chaotic behaviour can be controlled to a fair degree, moreover, all ...

  16. Double negative electromagnetic properties of percolated Fe53Ni47/Cu granular composites

    Science.gov (United States)

    Tsutaoka, Takanori; Massango, Herieta; Kasagi, Teruhiro; Yamamoto, Shinichiro; Hatakeyama, Kenichi

    2016-05-01

    Electromagnetic properties of hybrid composite materials containing copper and permalloy (Fe53Ni47 alloy) particles have been investigated in the RF to microwave frequency range up to 20 GHz. Double negative permittivity and permeability spectra have been observed in the percolated state of the hybrid composite material. The negative permittivity spectra in this composite can be attributed to the low frequency plasmonic state produced by the percolated Cu and permalloy cluster chains as well as the dielectric resonance of the isolated metal clusters. The refractive index spectra which were calculated from the measured permittivity and permeability data indicated the negative refraction from 200 MHz to 1.8 GHz. The near zero or zero refractive index state can be obtained near the two zero crossing frequencies in the refractive index spectra.

  17. 松果体及褪黑素对大鼠胸腺CD4+/CD8+T细胞分化发育的影响%Effects of pineal gland and melatonin on CD4+/CD8+ T cell subsets development in rat thymus

    Institute of Scientific and Technical Information of China (English)

    周瑞祥; 刘卉; 魏建恩; 黄云梅; 谢美容; 林建银

    2005-01-01

    目的:探讨松果体和褪黑素对胸腺T细胞分化发育的影响.方法:实验组为松果体摘除组和松果体摘除+褪黑素组.ABC法染胸腺CD4+、CD8+细胞.流式细胞术测定胸腺和血液T淋巴细胞CD4+、CD8+T亚类.结果:松果体摘除后胸腺明显萎缩,并随时间延长而加剧,补充褪黑素后胸腺重量逐渐恢复.松果体摘除后胸腺和血液中CD4+T细胞百分比无明显波动;胸腺CD8+T细胞比例上升,但血液CD8+T细胞比例则下降;补充褪黑素后胸腺CD4+T细胞在低剂量组略有下降,而高剂量组则显著升高,胸腺和血液CD8+T呈下降趋势,双阳性细胞比例恢复正常,双阴性细胞比例则上升.结论:松果体能显著影响CD8+T细胞的分化发育和释放,降低血液CD8+T细胞的比例.补充褪黑素能缓解相关影响.

  18. Study of the negative ion extraction mechanism from a double-ion plasma in negative ion sources

    Energy Technology Data Exchange (ETDEWEB)

    Goto, I.; Nishioka, S.; Hatayama, A. [Graduate school of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522 (Japan); Miyamoto, K. [Naruto University of Education, 748 Nakashima, Takashima, Naruto-cho, Naruto-shi, Tokushima 772-8502 (Japan)

    2015-04-08

    We have developed a 2D3V-PIC model of the extraction region, aiming to clarify the basic extraction mechanism of H{sup −} ions from the double-ion plasma in H{sup −} negative ion sources. The result shows the same tendency of the H{sup −} ion density n{sub H{sup −}} as that observed in the experiments, i.e.,n{sub H{sup −}} in the upstream region away from the plasma meniscus (H{sup −} emitting surface) has been reduced by applying the extraction voltage. At the same time, relatively slow temporal oscillation of the electric potential compared with the electron plasma frequency has been observed in the extraction region. Results of the systematic study using a 1D3V-PIC model with the uniform magnetic field confirm the result that the electrostatic oscillation is identified to be lower hybrid wave. The effect of this oscillation on the H{sup −} transport will be studied in the future.

  19. Ion-acoustic double layers in magnetized positive-negative ion plasmas with nonthermal electrons

    Science.gov (United States)

    El-Labany, S. K.; Sabry, R.; El-Taibany, W. F.; Elghmaz, E. A.

    2012-07-01

    The nonlinear ion-acoustic double layers (IADLs) in a warm magnetoplasma with positive-negative ions and nonthermal electrons are investigated. For this purpose, the hydrodynamic equations for the positive-negative ions, nonthermal electron density distribution, and the Poisson equation are used to derive a modified Zakharov-Kuznetsov (MZK) equation, in the small amplitude regime. It is found that compressive and rarefactive IADLs strongly depend on the mass and density ratios of the negative-to-positive ions as well as the nonthermal electron parameter. Also, it is shown that there are one critical value for the density ratio of the negative-to-positive ions ( ν), the ratio between unperturbed electron-to-positive ion density ( μ), and the nonthermal electron parameter ( β), which decide the existence of positive and negative IADLs. The present study is applied to examine the small amplitude nonlinear IADL excitations for the (H+, O2-) and (H+,H-) plasmas, where they are found in the D- and F-regions of the Earth's ionosphere. This investigation should be helpful in understanding the salient features of the nonlinear IADLs in either space or laboratory plasmas where two distinct groups of ions and non-Boltzmann distributed electrons are present.

  20. Negative Differential Resistance Probe for Interdot Interactions in a Double Quantum Dot Array.

    Science.gov (United States)

    Pozner, Roni; Lifshitz, Efrat; Peskin, Uri

    2015-05-07

    Colloidal quantum dots are free-standing nanostructures with chemically tunable electronic properties. In this work, we consider a new STM tip-double quantum dot (DQD)-surface setup with a unique connectivity, in which the tip is coupled to a single dot and the coupling to the surface is shared by both dots. Our theoretical analysis reveals a unique negative differential resistance (NDR) effect attributed to destructive interference during charge transfer from the DQD to the surface. This NDR can be used as a sensitive probe for interdot interactions in DQD arrays.

  1. Double negative elastic metamaterial design through electrical-mechanical circuit analogies.

    Science.gov (United States)

    Pope, Simon A

    2013-07-01

    Previous studies into solid elastic metamaterials which have a simultaneously negative effective bulk modulus and density have proposed designs for materials with relatively narrow bandwidths, because of the reliance on resonators to provide the dispersive material properties. Some of the proposed novel applications for metamaterials, such as invisibility cloaks and sub-wavelength lenses, generally require materials with inherently larger bandwidths for practical exploitation. In this paper, a well-known electromagnetic metamaterial design is used together with the electrical-mechanical circuit analogies to propose a simultaneously double negative elastic metamaterial design which does not suffer from the narrow bandwidth constraints of previous designs. An interesting consequence of the proposed design is that it has an effective wavelength which asymptotically goes to infinity with frequency.

  2. A New Compact Double-Negative Miniaturized Metamaterial for Wideband Operation

    Directory of Open Access Journals (Sweden)

    Md. Mehedi Hasan

    2016-10-01

    Full Text Available The aim of this paper is to introduce a compact double-negative (DNG metamaterial that exhibits a negative refractive index (NRI bandwidth of more than 3.6 GHz considering the frequency from 2 to 14 GHz. In this framework, two arms of the designed unit cell are split in a way that forms a Modified-Z-shape structure of the FR-4 substrate material. The finite integration technique (FIT-based Computer Simulation Technology (CST Microwave Studio is applied for computation, and the experimental setup for measuring the performance is performed inside two waveguide ports. Therefore, the measured data complies well with the simulated data of the unit cell at 0-degree and 90-degree rotation angles. The designed unit cell shows a negative refractive index from 3.482 to 7.096 GHz (bandwidth of 3.61 GHz, 7.876 to 10.047 GHz (bandwidth of 2.171 GHz, and 11.594 to 14 GHz (bandwidth of 2.406 GHz in the microwave spectra. The design also exhibits almost the same wide negative refractive index bandwidth in the major region of the C-band and X-band if it is rotated 90 degrees. However, the novelty of the proposed structure lies in its effective medium ratio of more than 4, wide bandwidth, and compact size.

  3. Nonlinear Localization due to a Double Negative Defect Layer in a One-Dimensional Photonic Crystal Containing Single Negative Material Layers

    Institute of Scientific and Technical Information of China (English)

    Munazza Zulfiqar Ali; Tariq Abdullah

    2008-01-01

    We investigate the effects of introducing a defect layer in a one-dimensional photonic crystal containing single negative material layers on the transmission properties.The width of the defect layer js taken to be the same or smaller than the period of the structure.Different cases of the defect layer being linear or nonlinear and double positive or double negative are discussed.It is found that only a nonlinear double negative layer givas rises to a localized mode within the zero-φeff gap in this kind of structure.It is also shown that the important characteristics of the nonlinear defect mode such as its frequency,its FWHM and the threshold of the associated bistability can be controlled by changing the widths of the defect layer and the host layers.

  4. Double Doppler effect in two-dimensional photonic crystal with negative effective index

    Science.gov (United States)

    Jiang, Qiang; Chen, Jiabi; Liang, Binming; Zhuang, Songlin

    2016-11-01

    The inverse Doppler effect in photonic crystal with negative refractive index had been proofed experimentally in our previous research. In this paper, we studied the spatial harmonics of Bloch wave propagating in such PhCs by FFT method. The lagging and front phase evolutions reveal that both backward wave and forward wave exist in these harmonics. Subsequently, we studied the double Doppler effect phenomenon that both the normal and inverse Doppler exist in one photonic crystal simultaneously by using the improved dynamic FDTD method which we made it suitable for dealing with moving objects. The simulative Doppler frequency shifts were consistent with the theoretical values. Our study provides a potential technology in measurement area.

  5. Simulation-based study of negative capacitance double-gate junctionless transistors with ferroelectric gate dielectric

    Science.gov (United States)

    Jiang, Chunsheng; Liang, Renrong; Wang, Jing; Xu, Jun

    2016-12-01

    In this work, a kind of negative capacitance double-gate junctionless transistor (NC-DG-JLT) with ferroelectric (FE) gate dielectric and metal-ferroelectric-metal-insulator-semiconductor (MFMIS) structure is proposed. It is demonstrated that NC-DG-JLTs can lower off-state current, improve on-state drain current, and lower subthreshold swing at the same time compared with its conventional DG JLT counterpart using numerical simulation. The steep subthreshold swing (SS detail. The low off-state current and high on/off current ratio could be obtained even for ultra-small transistors by optimizing the device parameters. NC-DG-JLTs have a great potential for low power dissipation applications.

  6. Analyses of a Dipole Antenna Loaded by a Cylindrical Shell of Double Negative (DNG Metamaterial

    Directory of Open Access Journals (Sweden)

    Khan M. Z. Shams

    2007-01-01

    Full Text Available The current distribution, input impedance, and radiation pattern of a cylindrical dipole antenna enclosed by a thin cylindrical shell of double negative (DNG metamaterial are computed using the piecewise sinusoidal Galerkin formulation. In the presence of the DNG shell, the dipole antenna exhibits three interesting characteristics. The input impedance shows potentials for wide bandwidth due to the relative insensitivity of the impedance with frequency. Within specific ranges of DNG material parameter values, the dipole shows resonance at much lower frequencies than its resonant frequency in free space. The dipole does not show change in the direction of the principal beam nor does it show signs of beam splitting and side lobes even when the antenna length approaches one and a half wavelength.

  7. Study of optical reflectance properties in 1D annular photonic crystal containing double negative (DNG) metamaterials

    Science.gov (United States)

    Srivastava, Sanjeev K.; Aghajamali, Alireza

    2016-05-01

    Theoretical investigation of photonic band gaps or reflection bands in one-dimensional annular photonic crystal (APC) containing double negative (DNG) metamaterials and air has been presented. The proposed structure consists of the alternate layers of dispersive DNG material and air immersed in free space. In order to study photonic band gaps we obtain the reflectance spectrum of the annular PC by employing the transfer matrix method (TMM) in the cylindrical waves for both TE and TM polarizations. In this work we study the effect of azimuthal mode number (m) and starting radius (ρ0) on the three band gaps viz. zero averaged refractive index (zero-nbar) gap, zero permittivity (zero- ε) and zero permeability (zero- μ) gaps. It is found that for m ≥ 1 , zero- μ gap appears in TE mode and zero- ε gap appears in TM mode. The width of both zero- μ and zero- ε gap increases by increasing m values, but the enhancement of zero- μ gap is more appreciable. Also, the effect of ρ0 on the three band gaps (reflection bands) of annular PC structure at the given m-number has been studied, for both TE and TM polarizations. The result shows that in both polarizations zero- ε and zero- μ gaps decreases when ρ0 increases, whereas zero-nbar gap remains invariant.

  8. Enhancement of H{sup -}/D{sup -} volume production in a double plasma type negative ion source

    Energy Technology Data Exchange (ETDEWEB)

    Fukumasa, Osamu; Nishimura, Hideki; Sakiyama, Satoshi [Yamaguchi Univ., Ube (Japan). Faculty of Engineering

    1997-02-01

    H{sup -}/D{sup -} production in a pure volume source has been studied. In our double plasma type negative ion source, both energy and density of fast electrons are well controlled. With the use of this source, the enhancement of H{sup -}/D{sup -} production has been observed. Namely, under the same discharge power, the extracted H{sup -}/D{sup -} current in the double plasma operation is higher than that in the single plasma operation. At the same time, measurements of plasma parameters have been made in the source and the extractor regions for these two cases. (author)

  9. Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy

    Science.gov (United States)

    Castaneda, Carlos A; Mittendorf, Elizabeth; Casavilca, Sandro; Wu, Yun; Castillo, Miluska; Arboleda, Patricia; Nunez, Teresa; Guerra, Henry; Barrionuevo, Carlos; Dolores-Cerna, Ketty; Belmar-Lopez, Carolina; Abugattas, Julio; Calderon, Gabriela; De La Cruz, Miguel; Cotrina, Manuel; Dunstan, Jorge; Gomez, Henry L; Vidaurre, Tatiana

    2016-01-01

    AIM To determine influence of neoadjuvant-chemotherapy (NAC) over tumor-infiltrating-lymphocytes (TIL) in triple-negative-breast-cancer (TNBC). METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays (TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response (pCR) (P = 0.0251) and outcome (P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections (ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. Post-NAC lesions with pCR had similar TIL levels than those without pCR (P = 0.6331). NAC produced a TIL decrease in full-face sections (P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival (DFS). Higher counts of CD3 in pre-NAC samples had longer overall-survival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR. CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related. PMID:27777881

  10. UNIFORM CONVERGENCE OF CES(A)RO MEANS OF NEGATIVE ORDER OF DOUBLE TRIGONOMETRIC FOURIER SERIES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper we prove that iff ∈ C([-π,π]2) and the function f is bounded partial p-variation for some p ∈ [1, +∞), then the double trigonometric Fourier series of a function f is uniformly (C;-α,-β) summable (α+ β< 1/p,α,β> 0) in the sense of Pringsheim. If α + β≥ 1/p, then there exists a continuous function f0 of bounded partial double trigonometric Fourier series of fo diverge over cubes.

  11. Double-spin-flip resonance of rhodium nuclei at positive and negative spin temperatures

    DEFF Research Database (Denmark)

    Tuoriniemi, J.T.; Knuuttila, T.A.; Lefmann, K.

    2000-01-01

    Sensitive SQUID-NMR measurements were used to study the mutual interactions in the highly polarized nuclear-spin system of rhodium metal. The dipolar coupling gives rise to a weak double-spin-flip resonance. The observed frequency shifts allow deducing separately the dipolarlike contribution...

  12. Effect of a mangosteen dietary supplement on human immune function: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Tang, Yu-Ping; Li, Peng-Gao; Kondo, Miwako; Ji, Hong-Ping; Kou, Yan; Ou, Boxin

    2009-08-01

    The effect of a mangosteen product containing multivitamins and essential minerals was tested on immune function and well-being in healthy adults. A randomized, double blinded, placebo-controlled study was conducted in 59 healthy human subjects (40-60 years old). Changes from baseline immune function were measured after a 30-day consumption of the mangosteen product and the placebo. The subjects' self-appraisal of their health status was also surveyed. A xanthone-rich mangosteen product intake increased mean values for peripheral T-helper cell frequency (P = .020) and reduced the serum C-reactive protein concentration (P = .014). Increases in peripheral CD4/CD8 double-positive (DP) T-cell frequency and serum complement C3, C4, and interleukin (IL)-1alpha concentrations were significantly higher in the experimental group than in the placebo group (DP, P = .038; C3, P = .017; C4, P = .031; IL-1alpha, P = .006). At the end of study, serum IL-1alpha and IL-1beta concentrations in the study group were significantly higher than that in the placebo group (IL-1alpha, P = .033; IL-1beta, P = .04). Furthermore, more participants in the experimental group reported greatly improved overall health status compared with participants receiving placebo (P = .001). The results indicated that the intake of an antioxidant-rich product significantly enhanced immune responses and improved the subject's self-appraisal on his or her overall health status.

  13. Effete of bronchoscopic cryotherapy and injection treatment on negative sputum conversion and immune function of multi-drug resistant tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Li Li

    2016-01-01

    Objective:To analyze the effect of bronchoscopic cryotherapy and injection treatment on negative sputum conversion and immune function of multi-drug resistant tuberculosis. Methods:A total of 60 patients with multi-drug resistant tuberculosis were randomly divided into observation group and control group, control group received 3DVThAE/15DVThE treatment and observation group received bronchoscopic cryotherapy and injection + 3DVThAE/15DVThE treatment. Differences in negative sputum conversion, serum ADA and inflammatory factors, immune function index values,etc. were compared between two groups after treatment.Results: Negative sputum conversion rate of observation group 6, 12 and 18 months after treatment were higher than those of control group (P<0.05); ADA, CRP and IL-10 levels of observation group after treatment were lower than those of control group, and IFN-γ level was higher than that of control group (P<0.05); peripheral blood CD3+ and CD4+T lymphocyte levels and CD4+/CD8+ ratio were higher than those of control group, and CD8+T lymphocyte level was lower than that of control group (P<0.05); IgA, IgM and IgG levels were higher than those of control group (P<0.05).Conclusions:Bronchoscopic cryotherapy and injection therapy can improve the condition in patients with multidrug-resistant tuberculosis and optimize treatment outcome.

  14. Viral blips during long-term treatment with standard or double dose lamivudine in HBe antigen negative chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate safety and effect on hepatitis B virus (HBV) suppression of a long-term treatment with lamivudine (LAM) at standard (100 mg/d) or double (200 mg/d) dose in chronic hepatitis B. METHODS: This was a case study with matched controls (1:3) in patients with chronic hepatitis B with anti-Hbe antibodies. RESULTS: Twelve patients received LAM 200 mg/d and 35 LAM 100 mg/d, for a median of 28 mo. A primary response (PR; I.e. Negative HBV-DNA with Amplicor assay) was achieved in 100% of LAM-200 patients and 83% of LAM-100 patients. A virological breakthrough occurred in 16.7 and 24.7%, respectively, of the PR-patients, with the appearance of typical LAM resistance mutations in all but one patient. Viremia blips (I.e. Transient HBV-DNA below 80 IU/Ml in patients who tested negative at Amplicor assay) were detected using a real time polymerase chain reaction (PCR) and occurred in seven out of nine patients with subsequent BT and in four out of 32 patients with end-of-study response (77.7% vs 12.5%; P = 0.001) at chi-square test). At the end of the study, 51.4% of LAM-100 patients and 83.3% of LAM-200 patients had remained stably HBV-DNA negative. Double-dose LAM was well tolerated. CONCLUSION: Long-term treatment of anti-Hbe positive chronic hepatitis B with double dose lamivudine causes a more profound and stable viral suppression as compared to conventional treatment.

  15. Design challenges in a double-blinded RCT study of music therapy for people suffering from szhizophrenia with negative symptoms

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2016-01-01

    . The study includes 120 participants. Participants in the experimental group become 25 hours of individual music therapy by specific trained music therapists working from a manual, wheras the control Group become 25 hours of being together with a care persone (trained by a music therapist) for music......The aim of this study is to examine if postiive results of International Cochrane Reviews on Music Therapy and Schizophrenia can be confirmed by a randomized controlled double blinded study on music therapy for people suffering from schizophrenia with extensive negative symptoms in Denmark...... of the design and the experiences of the first 30-40 cases involved in the study...

  16. Experimental Study of Single- and Double-Electron Detachment for Negative Carbon Ions Incident on Helium

    Institute of Scientific and Technical Information of China (English)

    HUANG Yong-Yi; WU Shi-Min; ZHANG Xue-Mei; LI Guang-Wu; LU Fu-Quan; YANG Fu-Jia

    2004-01-01

    Using the growth rate method, we obtain the single-electron detachment (SED) cross-sections for 5-30keV C-+He, and double-electron detachment (DED) cross-sections for 5-15keV C--+He. The SED cross-sections first increase with the increasing incident ion energy, and then decrease with further increase of the energy. The DED cross-sections increase with the increasing incident energy in the 5-15keV region.

  17. Dual-band double-negative-index fishnet metamaterial at millimeter-waves.

    Science.gov (United States)

    Navarro-Cía, Miguel; García-Meca, Carlos; Beruete, Miguel; Martínez, Alejandro; Sorolla, Mario

    2011-11-01

    An effective negative refractive index (NRI) is demonstrated and experimentally verified for the first two propagation bands of a fishnet-like metamaterial at millimeter-wave frequencies. The dual-band NRI behavior is achieved by engineering the diffraction order (±1, ±1) associated with the internal mode supported between holey layers to correspond with the second propagation band. In addition to the experimental interferometric technique that accounts for the handedness of the propagation, numerical results are given to predict the dual-band effective NRI and to confirm dual-band negative refraction for a prism composed of the proposed metamaterial.

  18. Proportions of CD4+, CD8+ and B cell subsets are not affected by exposure to HIV or to Cotrimoxazole prophylaxis in Malawian HIV-uninfected but exposed children.

    Science.gov (United States)

    Longwe, Herbert; Phiri, Kamija S; Mbeye, Nyanyiwe M; Gondwe, Thandile; Jambo, Kondwani C; Mandala, Wilson L

    2015-08-28

    As a result of successful PMTCT programs, children born from HIV-infected mothers are now effectively protected from contracting the infection. However, it is not well known whether in utero exposure to the virus and the subsequent exposure to Cotrimoxazole (CTX) prophylaxis affect the cell mediated immune system of the children. This observational prospective study was aimed at determining how CD4(+) T, CD8(+) T and B cell subsets varied in HIV-exposed but uninfected (HEU) children at different ages. We recruited HEU and HIV-unexposed and uninfected (HUU) children from 6 months of age and followed them up until they were 18 months old. HEU children received daily CTX prophylaxis beginning at 6 weeks of age until when 12 months of age. Venous blood samples were collected 6 monthly and analysed for different subsets of CD8(+) T, B cells and totalCD4(+) T cells. At 6 months of age, HEU children had a lower percentage of total CD4(+) T cells compared to HUU children and a lower proportion of naïve CD8(+) T cells but higher percentage of effector memory CD8(+) T cells compared to HUU children. HEU and HUU children had similar proportions of all B cell subsets at all ages. The study showed that the subtle variations in CD4(+) and CD8(+) T cell subsets observed at 6 months do not last beyond 12 months of age, suggesting that HEU children have a robust cell-mediated immune system during first year of life. This article report is not based on results of a controlled health-care intervention.

  19. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus by qRT-PCR

    Directory of Open Access Journals (Sweden)

    Iona E. Maher

    2014-03-01

    Full Text Available Investigation of the immune response of the koala (Phascolarctos cinereus is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV, which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala’s susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1 and Th2 lymphocyte responses are important to an individual’s susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala’s adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4, interleukin 6 (IL-6, interleukin 10 (IL-10 and interferon gamma (IFNγ along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A. Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not consistently up-regulated by any of the protocols. Expression of CD4 and CD8β was down-regulated by mitogen stimulation. We found that the reference genes GAPDH and 28s are valid for normalising cytokine expression by koala lymphocytes after mitogen stimulation.

  20. Hierarchy Low CD4+/CD8+ T-Cell Counts and IFN-γ Responses in HIV-1+ Individuals Correlate with Active TB and/or M.tb Co-Infection.

    Science.gov (United States)

    Shao, Lingyun; Zhang, Xinyun; Gao, Yan; Xu, Yunya; Zhang, Shu; Yu, Shenglei; Weng, Xinhua; Shen, Hongbo; Chen, Zheng W; Jiang, Weimin; Zhang, Wenhong

    2016-01-01

    Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. 164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (PHierarchy low CD8+ T-cell counts and effector function in HIV-1-infected individuals are correlated with both M.tb co-infection and active TB. Hierarchy low CD4+ T-cell counts and Th1 effector function in HIV-1+ individuals are associated with increased frequencies of active TB, but not M.tb co-infection.

  1. From Sunshine to Double Arrows: An Evaluation Window Account of Negative Compatibility Effects

    Science.gov (United States)

    Klauer, Karl Christoph; Dittrich, Kerstin

    2010-01-01

    In category priming, target stimuli are to be sorted into 2 categories. Prime stimuli preceding targets typically facilitate processing of targets when primes and targets are members of the same category, relative to the case in which both stem from different categories, a positive compatibility effect (PCE). But negative compatibility effects…

  2. Miniaturized dual-band antenna array with double-negative (DNG) metamaterial for wireless applications

    Science.gov (United States)

    Alqadami, Abdulrahman Shueai Mohsen; Jamlos, Mohd Faizal; Soh, Ping Jack; Rahim, Sharul Kamal Abdul; Vandenbosch, Guy A. E.; Narbudowicz, Adam

    2017-01-01

    A miniaturized dual-band antenna array using a negative index metamaterial is presented for WiMAX, LTE, and WLAN applications. This left-handed metamaterial plane is located behind the antenna array, and its unit cell is a combination of split-ring resonator, square electric ring resonator, and rectangular electrical coupled resonator. This enables the achievement of a metamaterial structure exhibiting both negative permittivity and permeability, which results in antenna size miniaturization, efficiency, and gain enhancement. Moreover, the proposed metamaterial antenna has realized dual-band operating frequencies compared to a single frequency for normal antenna. The measured reflection coefficient (S11) shows a 50.25% bandwidth in the lower band (from 2.119 to 3.058 GHz) and 4.27% in the upper band (from 5.058 to 5.276 GHz). Radiation efficiency obtained in the lower and upper band are >95 and 80%, respectively.

  3. Two-dimensional locally resonant elastic metamaterials with chiral comb-like interlayers: Bandgap and simultaneously double negative properties.

    Science.gov (United States)

    Wang, Yan-Feng; Wang, Yue-Sheng; Zhang, Chuanzeng

    2016-06-01

    In this paper, bandgap and dynamic effective properties of two-dimensional elastic metamaterials with a chiral comb-like interlayer are studied by using the finite element method. The effects of the geometrical parameters of the chiral comb-like interlayer on the band edges are investigated and discussed. Combined with the analysis of the vibration modes at the band edges, equivalent spring-mass/pendulum models are developed to investigate the mechanisms of the bandgap generation. The analytically predicted results of the band edges, including the frequency where the double negative properties appear, and the numerical ones are generally in good agreement. The research findings in this paper have relevant engineering applications of the elastic metamaterials in the low frequency range.

  4. Design challenges in a double-blinded study of music therapy for people suffering from szhizophrenia with negative symptoms

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2016-01-01

    The aim of this study is to examine if postiive results of International Cochrane Reviews on Music Therapy and Schizophrenia can be confirmed by a randomized controlled double blinded study on music therapy for people suffering from schizophrenia with extensive negative symptoms in Denmark....... The study includes 120 participants. Participants in the experimental group become 25 hours of individual music therapy by specific trained music therapists working from a manual, wheras the control Group become 25 hours of being together with a care persone (trained by a music therapist) for music...... listening from a selected playlist. Ethical refelctions around the design will be presented, and the possibilities of keeping the examination process blinded or not blinded to the participants with be shared. As this examination is currently running, the focus will be on the Development of abd application...

  5. Investigation of the negative differential resistance reproducibility in AlN/GaN double-barrier resonant tunnelling diodes

    Energy Technology Data Exchange (ETDEWEB)

    Boucherit, M.; Soltani, A.; Rousseau, M.; Deresmes, D.; Berthe, M.; Durand, C.; De Jaeger, J.-C. [IEMN/UMR-CNRS 8520, Universite Lille1, PRES Universite Lille Nord de France (France); Monroy, E. [Equipe mixte CEA-CNRS-UJF Nanophysique et Semiconducteurs, DRFMC/SP2M/PSC, CEA-Grenoble (France)

    2011-10-31

    AlN/GaN double-barrier resonant tunnelling diodes were grown by molecular beam epitaxy on GaN/sapphire template and processed into mesa diameters from 2 {mu}m to 4 {mu}m. The current-voltage characteristics were carried out in direct current operation and under-high vacuum. A sharp negative differential resistance (NDR) was detected in the forward bias at 120 K. The NDR was observed for the mesa size of 2 {mu}m at 4 V with a peak-to-valley current ratio of 3.5. The measurement conditions were chosen to make NDR reproducible more than 50 times and apparent in both scan voltage directions after electrical treatment.

  6. Properties of the Band Gaps in 1D Ternary Lossy Photonic Crystal Containing Double-Negative Materials

    Directory of Open Access Journals (Sweden)

    Alireza Aghajamali

    2014-01-01

    Full Text Available Theoretically, the characteristics matrix method is employed to investigate and compare the properties of the band gaps of the one-dimensional ternary and binary lossy photonic crystals which are composed of double-negative and double-positive materials. This study shows that by varying the angle of incidence, the band gaps for TM and TE waves behave differently in both ternary and binary lossy structures. The results demonstrate that, by increasing the angle of incidence for the TE wave, the width and the depth of zero-n¯, zero-μ, and Bragg gap increase in both ternary and binary structures. On the other hand, the enhancement of the angle of incidence for the TM wave contributes to reduction of the width and the depth of the zero-n¯ and Bragg gaps, and they finally disappear for incidence angles greater than 50° and 60° for the binary structure and 40° and 45° for the ternary structures, respectively. In addition, the details of the edges of the band gaps variations as a function of incidence angle for both structures are studied.

  7. Waves in hyperbolic and double negative metamaterials including rogues and solitons.

    Science.gov (United States)

    Boardman, A D; Alberucci, A; Assanto, G; Grimalsky, V V; Kibler, B; McNiff, J; Nefedov, I S; Rapoport, Yu G; Valagiannopoulos, C A

    2017-03-17

    considered with a model of the response of hyperbolic metamaterials in terms of the homogenisation ('effective medium') approach. The model has a macroscopic dielectric tensor encompassing at least one negative eigenvalue. It is shown that light propagating in the presence of hyperbolic dispersion undergoes negative (anomalous) diffraction. The theory is ten broadened out to include the influence of the orientation of the optical axis with respect to the propagation wave vector. Optical rogue waves are discussed in terms of how they are influenced, but not suppressed, by a metamaterial background. It is strongly discussed that metamaterials and optical rogue waves have both been making headlines in recent years and that they are, separately, large areas of research to study. A brief background of the inevitable linkage of them is considered and important new possibilities are discussed. After this background is revealed some new rogue wave configurations combining the two areas are presented alongside a discussion of the way forward for the future.

  8. A Primary Study of the Subgroups of T Lymphocytes in MHV-3 Induced Chronic Viral Hepatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice, ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units (PFU) of MHV-3 intraperitoneally. The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin (HE) staining method from 2 days post MHV-3 infection. The ratios of T cell subsets including CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8-, CD3+CD4+CD25+, CD3+CD4+CD25- and CD3+CD4-CD25+ T lymphocyte of total T lymphocytes in blood, spleen and liver were examined at 0, 2, 4, 6,8, 10, 12, 15, 20, 25, 30, 40 days post MHV-3 infection by flow cytosorting. We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection. The double negative T cell (DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 2 days post MHV-3 infection in C3H/Hej mice, and CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD25- and CD3+CD4-CD25+ T cell ratios decreased accordingly. In conclusion, the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence. Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice.The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection. Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.

  9. Nucleoprotein structure of the CD4 locus: Implications for the mechanisms underlying CD4 regulation during T cell development

    OpenAIRE

    Yu, Ming; Wan, Mimi; Zhang, Jianmin; Wu, Jie; Khatri, Rohini; Chi, Tian

    2008-01-01

    The CD4 gene is regulated in a stage-specific manner during T cell development, being repressed in CD4−CD8− double-negative (DN) and CD8 cells, but expressed in CD4+CD8+ double-positive (DP) and CD4 cells. Furthermore, the expression/repression pattern is reversible in developing (DN and DP) thymocytes, but irreversible in mature (CD4 and CD8) T cells. Here, we explored the molecular mechanisms underlying this complex mode of regulation by examining the nucleoprotein structure of the CD4 locu...

  10. Effects of negative air ions on oxygen uptake kinetics, recovery and performance in exercise: a randomized, double-blinded study

    Science.gov (United States)

    Nimmerichter, Alfred; Holdhaus, Johann; Mehnen, Lars; Vidotto, Claudia; Loidl, Markus; Barker, Alan R.

    2014-09-01

    Limited research has suggested that acute exposure to negatively charged ions may enhance cardio-respiratory function, aerobic metabolism and recovery following exercise. To test the physiological effects of negatively charged air ions, 14 trained males (age: 32 ± 7 years; : 57 ± 7 mL min-1 kg-1) were exposed for 20 min to either a high-concentration of air ions (ION: 220 ± 30 × 103 ions cm-3) or normal room conditions (PLA: 0.1 ± 0.06 × 103 ions cm-3) in an ionization chamber in a double-blinded, randomized order, prior to performing: (1) a bout of severe-intensity cycling exercise for determining the time constant of the phase II response ( τ) and the magnitude of the slow component (SC); and (2) a 30-s Wingate test that was preceded by three 30-s Wingate tests to measure plasma [adrenaline] (ADR), [nor-adrenaline] (N-ADR) and blood [lactate] (BLac) over 20 min during recovery in the ionization chamber. There was no difference between ION and PLA for the phase II τ (32 ± 14 s vs. 32 ± 14 s; P = 0.7) or SC (404 ± 214 mL vs 482 ± 217 mL; P = 0.17). No differences between ION and PLA were observed at any time-point for ADR, N-ADR and BLac as well as on peak and mean power output during the Wingate tests (all P > 0.05). A high-concentration of negatively charged air ions had no effect on aerobic metabolism during severe-intensity exercise or on performance or the recovery of the adrenergic and metabolic responses after repeated-sprint exercise in trained athletes.

  11. Effectiveness of rivastigmine on positive, negative, and cognitive symptoms of schizophrenia: a double-blind clinical trial

    Science.gov (United States)

    Shoja Shafti, Saeed; Azizi Khoei, Abbas

    2016-01-01

    Background: Several lines of evidence suggest that the cholinergic system may be disrupted in schizophrenia and so this may contribute to the cognitive impairments of schizophrenic patients. Because such deficits do not respond to neuroleptic treatment, different approaches have been done by acetylcholinesterase inhibitors (AChEIs). The objective of the present assessment was to evaluate the safety and clinical effects of rivastigmine, as an adjunctive drug, on the clinical symptoms of schizophrenia. Methods: A total of 46 patients with a diagnosis of schizophrenia entered into a 12-week, double-blind, clinical trial for random assignment to rivastigmine or placebo, as adjuvant to their current antipsychotic medication. Positive and Negative Symptom Scale (PANSS) and Mini Mental State Examination (MMSE) had been used as the primary outcome measures. Clinical Global Impressions- Improvement (CGI-I) Scale and Extrapyramidal Symptom Rating Scale (ESRS) had been used as the secondary measures. Treatment efficacy was evaluated by a Student’s t test and repeated-measures analysis of variance (ANOVA). Statistical significance was defined as a two-sided p value ⩽ 0.05. Cohen’s standard (d) and correlation measures of effect size (r) had been calculated for comparing baseline to endpoint changes. Results: According to the findings, except for significant enhancement of MMSE by rivastigmine (p < 0.001), no significant improvement in PANSS (negative symptoms), PANSS (positive symptoms), and PANSS (general psychopathology) was evident in the target group. Also, except for significant improvement of CGI-I by rivastigmine in intragroup analysis, no significant effectiveness was evident in between-group analysis or repeated-measures ANOVA. ESRS, also, did not show any significant alteration in either group. Effect size (ES) analysis showed a large improvement in MMSE by rivastigmine. Conclusions: According to the findings, while rivastigmine could not induce significant

  12. Delayed functional maturation of natural regulatory T cells in the medulla of postnatal thymus: role of TSLP

    Directory of Open Access Journals (Sweden)

    Knudsen Geoffry

    2006-04-01

    Full Text Available Abstract Background Generation of functional CD4+CD8-CD25+ regulatory T cells (Treg in the murine thymus depends on FoxP3. Removal of the thymus from neonatal mice has been shown to result in a multiple organ autoimmune disease phenotype that can be prevented by introducing the FoxP3+ Treg population to the animal. It has therefore, been proposed that functional FoxP3+ Treg cells are not made in the neonatal thymus; however, it remains unclear when and where functional FoxP3+CD4+CD8-CD25+ thymocytes are generated in postnatal thymus. Results We report that neither FoxP3 mRNA nor protein is expressed in CD4+CD8-CD25+, or CD4+CD8-CD25- thymocytes until 3–4 days post birth, despite the presence of mature CD4+CD8-CD25+/- thymocytes in the thymus by 1–2 days after birth. FoxP3-CD4+CD8-CD25+ thymocytes from day 2 newborn mice show no Treg activity. Interestingly, we are able to detect low numbers of FoxP3+ thymocytes dispersed throughout the medullary region of the thymus as early as 3–4 days post birth. Expression of FoxP3 is induced in embryonic day 17 fetal thymus organ culture (FTOC after 4–6 days of in vitro culture. Treatment of FTOCs with thymic stromal derived lymphopoietin (TSLP enhanced expression of FoxP3, and blocking the TSLP receptor reduces FoxP3 expression in FTOC. Furthermore, TSLP stimulates FoxP3 expression in purified CD4+CD8- thymocytes, but not in CD4+CD8+, CD4-CD8+ and CD4-CD8- thymocytes. Conclusion Expression of FoxP3 or Treg maturation is ontogenically distinct and kinetically delayed from the generation of CD4+CD8-CD25+ or CD4+CD8-CD25- thymocytes in the postnatal thymus. TSLP produced from medullary thymic epithelia cells (mTEC contributes to the expression of FoxP3 and the maturation of natural regulatory T cells. Overall, these results suggest that the development of Treg cells requires paracrine signaling during late stages of thymocyte maturation that is distinct from signaling during positive or negative

  13. Germline genetic variants disturbing the Let-7/LIN28 double-negative feedback loop alter breast cancer susceptibility.

    Directory of Open Access Journals (Sweden)

    Ao-Xiang Chen

    2011-09-01

    Full Text Available Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7-induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300 demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR of 1.25 (P = 0.0091, which was successfully replicated in a second independent study (n = 1,156 with community-based controls. The combined P-value of the two studies was 8.0 × 10⁻⁵. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk.

  14. Germline genetic variants disturbing the Let-7/LIN28 double-negative feedback loop alter breast cancer susceptibility.

    Science.gov (United States)

    Chen, Ao-Xiang; Yu, Ke-Da; Fan, Lei; Li, Ji-Yu; Yang, Chen; Huang, A-Ji; Shao, Zhi-Ming

    2011-09-01

    Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7-induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0 × 10⁻⁵. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk.

  15. Lymphoma-like T cell infiltration in liver is associated with increased copy number of dominant negative form of TGFβ receptor II.

    Directory of Open Access Journals (Sweden)

    Weici Zhang

    Full Text Available Hepatosplenic T cell lymphoma (HSTCL is a distinct and lethal subtype of peripheral T cell lymphoma with an aggressive course and poor outcome despite multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor response to treatment highlight the need to define the malignant process and identify molecular targets with potential for successful therapeutic interventions. Herein, we report that mice homozygously expressing a dominant negative TGFβRII (dnTGFβRII under the control of the CD4 promoter spontaneously develop lymphoma-like T cell infiltration involving both spleen and liver. Splenomegaly, hepatomegaly and liver dysfunction were observed in homozygous dnTGFβRII mice between 10 weeks and 10 months of age associated with a predominant infiltration of CD4(-CD8(-TCRβ(+NK1.1(+ or CD8(+TCRβ(+NK1.1(- T cell subsets. Notch 1 and c-Myc expression at the mRNA levels were significantly increased and positively correlated with the cell number of lymphoid infiltrates in the liver of dnTGFβRII homozygous compared to hemizygous mice. Further, 2×10(4 isolated lymphoma-like cells transplant disease by adoptive cell transfers. Collectively, our data demonstrate that increased copy number of dnTGFβRII is critical for development of lymphoma-like T cell infiltration.

  16. Production of negative hydrogen ions in a large multicusp ion source with double-magnetic filter configuration

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A.; Takeiri, Y.; Kaneko, O.; Oka, Y.; Wada, M.; Kuroda, T.

    1992-05-01

    The production of the negative hydrogen ions in a large multicusp ion source has been investigated in a double-magnetic filter (DMF) configuration. In the DMF configuration, the energetic electrons are trapped by the mirror of a magnetic multicusp field, and only the thermal electrons are present in the center of the arc chamber. A large amount of H[sup -] ions of more than 1 x 10[sup 12] cm[sup -3] are produced in the center region. The electron current extracted with the H[sup -] ions can be suppressed by a magnetic filter field in front of a plasma grid without affecting the H[sup -] ion current. The experimental data obtained in the DMF configuration are compared with those obtained in a single-magnetic filter (SMF) configuration. In the SMF configuration, the energetic electrons are present in the center region, and the magnetic filter in front of a plasma grid reduces the electron density and temperature, which results in the reduction of H[sup -] ion current as well as the electron current. The extracted electron current and the optimum gas pressure for the H[sup -] ion current are lower in the DMF configuration that those in the SMF configuration. (author).

  17. Production of negative hydrogen ions in a large multicusp ion source with double-magnetic filter configuration

    Energy Technology Data Exchange (ETDEWEB)

    Ando, A.; Takeiri, Y.; Kaneko, O.; Oka, Y.; Wada, M.; Kuroda, T.

    1992-05-01

    The production of the negative hydrogen ions in a large multicusp ion source has been investigated in a double-magnetic filter (DMF) configuration. In the DMF configuration, the energetic electrons are trapped by the mirror of a magnetic multicusp field, and only the thermal electrons are present in the center of the arc chamber. A large amount of H{sup -} ions of more than 1 x 10{sup 12} cm{sup -3} are produced in the center region. The electron current extracted with the H{sup -} ions can be suppressed by a magnetic filter field in front of a plasma grid without affecting the H{sup -} ion current. The experimental data obtained in the DMF configuration are compared with those obtained in a single-magnetic filter (SMF) configuration. In the SMF configuration, the energetic electrons are present in the center region, and the magnetic filter in front of a plasma grid reduces the electron density and temperature, which results in the reduction of H{sup -} ion current as well as the electron current. The extracted electron current and the optimum gas pressure for the H{sup -} ion current are lower in the DMF configuration that those in the SMF configuration. (author).

  18. Coordination of Double Strand Break Repair and Meiotic Progression in Yeast by a Mek1- Ndt80 Negative Feedback Loop.

    Science.gov (United States)

    Prugar, Evelyn; Burnett, Cameron; Chen, Xiangyu; Hollingsworth, Nancy M

    2017-03-01

    During meiosis, homologous chromosomes are physically connected by crossovers and sister chromatid cohesion. Interhomolog crossovers are generated by the highly regulated repair of programmed double strand breaks (DSBs). The meiosis-specific kinase, Mek1, is critical for this regulation. Mek1 down-regulates the mitotic recombinase Rad51, indirectly promoting interhomolog strand invasion by the meiosis-specific recombinase, Dmc1. Mek1 also promotes the formation of crossovers that are distributed throughout the genome by interference and is the effector kinase for a meiosis-specific checkpoint that delays entry into Meiosis I until DSBs have been repaired. The target of this checkpoint is a meiosis-specific transcription factor, Ndt80, which is necessary to express the polo-like kinase, CDC5, and the cyclin, CLB1, thereby allowing completion of recombination and meiotic progression. This work shows that Mek1 and Ndt80 negatively feedback on each other such that when DSB levels are high, Ndt80 is inactive due to high levels of Mek1 activity. As DSBs are repaired, chromosomes synapse and Mek1 activity is reduced below a threshold that allows activation of Ndt80. Ndt80 transcription of CDC5 results in degradation of Red1, a meiosis-specific protein required for Mek1 activation, thereby abolishing Mek1 activity completely. Elimination of Mek1 kinase activity allows Rad51-mediated repair of any remaining DSBs. In this way, cells do not enter Meiosis I until recombination is complete and all DSBs are repaired.

  19. Electric-line-source illumination of a circular cylinder of lossless double-negative material: an investigation of near field, directivity, and radiation resistance

    DEFF Research Database (Denmark)

    Arslanagic, Samel; Breinbjerg, Olav

    2006-01-01

    This work investigates the properties of an antenna-like configuration with an electric line source radiating in the presence of a double-negative circular cylinder. First, the analytical eigenfunction-series solution is derived. Second, this solution is employed in numerical calculations to stud...

  20. Safety and Efficacy of Tien-Hsien Liquid Practical in Patients with Refractory Metastatic Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase IIa Trial

    Directory of Open Access Journals (Sweden)

    Wen-Hung Kuo

    2012-01-01

    Full Text Available To evaluate the safety and efficacy of Tien-Hsien Liquid Practical (THL-P, a Chinese herbal mixture, in patients with refractory metastatic breast cancer, we performed a randomized, double-blind, placebo-controlled, parallel-group, phase IIa pilot trial. Patients were randomly assigned to either receive THL-P or matching placebo and followed up every 4 weeks for 24 weeks. The primary endpoint was changes in the global health status/quality of life (GHS/QOL scale. The secondary endpoints were changes in functional and symptom scales, immunomodulating effects, and adverse events. Sixty-three patients were enrolled between June 2009 and June 2011. The intent-to-treat population included 28 patients in the THL-P group and 11 patients in the placebo group. Compared to the placebo group, the THL-P group had significant improvement from baseline to last visit in GHS/QOL (41.7 versus −33.3; P<0.05, CD3, CD4/CD8, CD19, CD16+56 positive cells (P<0.05, and higher levels of physical, role, emotional, and cognitive functioning, as well as decreased fatigue and systemic side effects. Treatment-related adverse events were mild constipation and localized itching, and no serious adverse events were reported. THL-P appears to be a safe alternative adjuvant treatment for patients with refractory metastatic breast cancer, as it effectively improves QOL and palliates cancer-related symptoms.

  1. Cooperation of Gata3, c-Myc and Notch in malignant transformation of double positive thymocytes.

    Science.gov (United States)

    van Hamburg, Jan Piet; de Bruijn, Marjolein J W; Dingjan, Gemma M; Beverloo, H Berna; Diepstraten, Hans; Ling, Kam-Wing; Hendriks, Rudi W

    2008-06-01

    Gata transcription factors are critical regulators of proliferation and differentiation implicated in various human cancers, but specific genes activated by Gata proteins remain to be identified. We previously reported that enforced expression of Gata3 during T cell development in CD2-Gata3 transgenic mice induced CD4(+)CD8(+) double-positive (DP) T cell lymphoma. Here, we show that the presence of the DO11.10 T-cell receptor transgene, which directs DP cells towards the CD4 lineage, resulted in enhanced lymphoma development and a dramatic increase in thymocyte cell size in CD2-Gata3 transgenic mice. CD2-Gata3 DP cells expressed high levels of the proto-oncogene c-Myc but the Notch1 signaling pathway, which is known to induce c-Myc, was not activated. Gene expression profiling showed that in CD2-Gata3 lymphoma cells transcription of c-Myc and its target genes was further increased. A substantial fraction of CD2-Gata3 lymphomas had trisomy of chromosome 15, leading to an increased c-Myc gene dose. Interestingly, most lymphomas showed high expression of the Notch targets Deltex1 and Hes1, often due to activating Notch1 PEST domain mutations. Therefore, we conclude that enforced Gata3 expression converts DP thymocytes into a pre-malignant state, characterized by high c-Myc expression, whereby subsequent induction of Notch1 signaling cooperates to establish malignant transformation. The finding that Gata3 regulates c-Myc expression levels, in a direct or indirect fashion, may explain the parallel phenotypes of mice with overexpression or deficiency of either of the two transcription factors.

  2. A post hoc analysis of negative symptoms and psychosocial function in patients with schizophrenia: a 40-week randomized, double-blind study of ziprasidone versus haloperidol followed by a 3-year double-blind extension trial.

    Science.gov (United States)

    Stahl, Stephen M; Malla, Ashok; Newcomer, John W; Potkin, Steven G; Weiden, Peter J; Harvey, Philip D; Loebel, Antony; Watsky, Eric; Siu, Cynthia O; Romano, Steve

    2010-08-01

    Schizophrenia is a persistent, lifelong illness such that enduring functional improvements may only occur over the course of years [corrected].This post hoc analysis in stable outpatients with schizophrenia investigated the negative symptom efficacy and treatment outcomes of ziprasidone (80-160 mg/d given twice a day, mean modal dose of 112 mg/d; and 80-120 mg/d given every day, mean modal dose of 96 mg/d) versus haloperidol (5-20 mg/d, mean modal dose of 12 mg/d) in a randomized, 40-week, double-blind study, followed by a double-blind continuation trial that extended up to 156 additional weeks. Symptomatic and functional recovery criteria were met when subjects attained both negative symptom remission and adequate psychosocial functioning based on the 4 Quality-of-Life subscales (instrumental role, interpersonal relations, participation in community, and intrapsychic foundations). Negative symptom remission (P = 0.005), as well as sustained adequate functioning (6 months) in instrumental role (P = 0.04) and participation in community (P = 0.02), was associated with significantly shorter time to remission in the ziprasidone 80 to 160 mg group than in the haloperidol group, as was the combination of symptomatic and functional recovery during the 196-week double-blind study period. A similar pattern was observed for the ziprasidone 80 to 120 mg group, which showed significant differences versus haloperidol in negative symptom remission and instrumental role functioning (but not other Quality-of-Life subscale measures). The clinically relevant outcome differences detected in this post hoc exploratory analysis support the potential for both enhanced remission in negative symptoms and psychosocial recovery during long-term treatment with an atypical agent and add to our understanding regarding the degree to which negative symptom remission can be attained in the maintenance phase.

  3. Double-blind, randomized sham controlled study of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia.

    Science.gov (United States)

    Rabany, Liron; Deutsch, Lisa; Levkovitz, Yechiel

    2014-07-01

    Negative symptoms and cognitive deficits are considered core symptoms of schizophrenia, yet treatment for them remains inadequate. Deep-transcranial magnetic stimulation (TMS) is a novel technology that enables non-invasive stimulation of deep layers of the prefrontal cortex. Preliminary evidence suggests that deep-TMS could be effective in the treatment of negative symptoms and cognitive deficits. The current study is the first double-blind, randomized sham-controlled study to examine the feasibility of deep-TMS add-on treatment for negative symptoms and cognitive deficits in schizophrenia. Twenty daily H1 deep-TMS treatments (20Hz, 120% MT) were delivered, in a double-blind, randomized sham-controlled design (n=30). Extensive clinical and cognitive assessments were carried out throughout the study and for an additional one month follow-up period. The results indicate that at the end of the treatment period, negative symptoms (as indicated by the Scale for the Assessment of Negative Symptoms (SANS)) significantly reduced in the TMS group (-7.7), but not in the sham group (-1.9). Differences between the groups were not statistically significant.

  4. Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.

    Directory of Open Access Journals (Sweden)

    Ailin Lepletier

    2014-10-01

    Full Text Available The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P, a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.

  5. Comparison of combined-field and electric-field volume integral equations for modelling double-negative metematerial antennas and scatterers

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Breinbjerg, Olav

    2008-01-01

    Two volume integral equation formulations for modelling magneto-dielectric objects are compared in terms of accuracy and computational efficiency. The first is the combined-field integral equation (CFVIE), in which the unknown quantities are both the electric and magnetic fields, while the second...... is the electric-field integral equation (EFVIE) with a single unknown quantity - the electric field. A resonant double-negative metamaterial spherical shell is analysed as an example....

  6. Comparison of combined-field and electric-field volume integral equations for modelling double-negative metematerial antennas and scatterers

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Breinbjerg, Olav

    2008-01-01

    Two volume integral equation formulations for modelling magneto-dielectric objects are compared in terms of accuracy and computational efficiency. The first is the combined-field integral equation (CFVIE), in which the unknown quantities are both the electric and magnetic fields, while the second...... is the electric-field integral equation (EFVIE) with a single unknown quantity - the electric field. A resonant double-negative metamaterial spherical shell is analysed as an example....

  7. Disturbance of the let-7/LIN28 double-negative feedback loop is associated with radio- and chemo-resistance in non-small cell lung cancer.

    Science.gov (United States)

    Yin, Jun; Zhao, Jian; Hu, Weimin; Yang, Guangping; Yu, Hui; Wang, Ruihao; Wang, Linjing; Zhang, Guoqian; Fu, Wenfan; Dai, Lu; Li, Wanzhen; Liao, Boyu; Zhang, Shuxu

    2017-01-01

    Radio- and chemo-resistance represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC) and the underlying molecular mechanisms are not known. In the present study, during induction of radio- or chemo-resistance in NSCLC cells, dynamic analyses revealed that decreased expression of let-7 induced by irradiation or cisplatin resulted in increased expression of its target gene LIN28, and increased expression of LIN28 then contributed to further decreased expression of let-7 by inhibiting its maturation and biogenesis. Moreover, we showed that down-regulation of let-7 and up-regulation of LIN28 expression promoted resistance to irradiation or cisplatin by regulating the single-cell proliferative capability of NSCLC cells. Consequently, in NSCLC cells, let-7 and LIN28 can form a double-negative feedback loop through mutual inhibition, and disturbance of the let-7/LIN28 double-negative feedback loop induced by irradiation or chemotherapeutic drugs can result in radio- and chemo-resistance. In addition, low expression of let-7 and high expression of LIN28 in NSCLC patients was associated significantly with resistance to radiotherapy or chemotherapy. Therefore, our study demonstrated that disturbance of the let-7/LIN28 double-negative feedback loop is involved in the regulation of radio- and chemo-resistance, and that let-7 and LIN28 could be employed as predictive biomarkers of response to radiotherapy or chemotherapy in NSCLC patients.

  8. No negative symptoms in healthy volunteers after single doses of amisulpride, aripiprazole, and haloperidol: a double-blind placebo-controlled trial.

    Science.gov (United States)

    Park, Chul-Hyun; Park, Tae-Won; Yang, Jong-Chul; Lee, Keon-Hak; Huang, Guang-Biao; Tong, Zhao; Park, Myung-Sook; Chung, Young-Chul

    2012-03-01

    Noncompliance and poor outcome in patients with schizophrenia are closely related to the negative symptoms secondary to antipsychotics. No controlled study has evaluated whether amisulpride and aripiprazole induce negative symptoms. The aim of this study was to assess the effects of single doses of amisulpride, aripiprazole, haloperidol, and risperidone in healthy volunteers. Seventy-eight young volunteers took part in this double-blind, randomized, placebo-controlled, parallel study of four antipsychotics: 400 mg amisulpride, 10 mg aripiprazole, 3 mg haloperidol, and 2 mg risperidone. Assessments of negative symptoms were done 4 h after administration using both subjective rating scales (Neuroleptic Induced Deficit Syndrome Scale and Subjective Deficit Syndrome Scale) and an objective rating scale (Scale for the Assessment of Negative Symptoms). Risperidone only produced significant increases on the avolition score of the Neuroleptic Induced Deficit Syndrome Scale and blunted affect and alogia scores of the Scale for the Assessment of Negative Symptoms compared with placebo. The effect on blunted affect persisted after controlling for mental sedation. Amisulpride, aripiprazole, and haloperidol did not induce negative symptoms. Aripiprazole and risperidone induced mild extrapyramidal symptoms. The most common adverse events were somnolence and cognitive slowing. These data indicate that a single risperidone dose induces negative symptoms in normal volunteers, whereas amisulpride, aripiprazole, and haloperidol do not. These characteristics of antipsychotics should be considered when choosing optimal drugs for patients with psychosis.

  9. Characterization of the diffuse mucosal associated lymphoid tissue of feline small intestine.

    Science.gov (United States)

    Roccabianca, P; Woo, J C; Moore, P F

    2000-06-30

    Characterization of the feline intestinal mucosal associated lymphoid tissue (MALT) will facilitate investigation of intestinal disease in the cat and promote the cat as an animal model for a range of human diseases which involve the intestinal lymphoid tissue. This includes inflammatory bowel disease, viral and non-viral associated intestinal lymphomas and immunodeficiency associated syndromes. Morphologic and phenotypic characterization of the normal small intestinal diffuse MALT in 22 SPF cats was performed using flow cytometry and cytology on isolated intestinal leukocytes from the intra-epithelial and lamina proprial compartments, as well as immunohistology on tissues from the feline duodenum, jejunum and ileum. The intra-epithelial compartment (IEC) was dominated by lymphocytes (>85%) which frequently contained intracytoplasmic granules. The most striking findings in the IEC were the elevated percentages of CD8 alpha+ lymphocytes (40%), presumed to express CD8 alpha alpha chains, and CD4-/CD8- (double negative) lymphocytes (44%), and the consistent presence of a minor subpopulation of CD3+/CD11d+ IELs (6%). Small percentages of CD4+ lymphocytes (10%) were observed such that the IEL CD4:CD8 ratio (0.25) was low. The LPC also contained a majority of T cells and few plasma cells. However, this compartment had reduced percentages of CD8 alpha+ lymphocytes (28%) and increased percentages of CD4+ lymphocytes (27%) relative to the IEC. However, the LPL CD4:CD8 ratio (1.0) remained low compared with the ratio in peripheral blood. In feline MALT, MHC class II expression was lower than in other peripheral lymphoid compartments. The results of this study provide important reference values for future investigations involving feline intestinal lymphocytes and demonstrates that the leukocyte distribution and phenotypic characteristics of the feline diffuse MALT appear largely similar to the murine, rat and human counterparts.

  10. Maternal education mitigates the negative effects of higher income on the double burden of child stunting and maternal overweight in rural Mexico.

    Science.gov (United States)

    Leroy, Jef L; Habicht, Jean-Pierre; González de Cossío, Teresa; Ruel, Marie T

    2014-05-01

    Globally, the rate at which maternal overweight and obesity increase with rising wealth is higher than the accompanying decline in the prevalence of child stunting, resulting in the double burden of malnutrition. The positive association between household wealth and child linear growth is larger in households with a more educated mother. However, whether a similar positive and synergistic association between maternal education and household wealth is observed for maternal body weight is unknown. Our objective was to assess the potential protective role of maternal education in the etiology of the double burden of malnutrition (stunted child with an overweight mother). We used data on 1547 nonpregnant mothers (aged 18-49 y) and their children (aged 0-5 y) collected in a cross-sectional survey in 235 rural communities in southern Mexico. Child height-for-age Z-score and maternal body weight were regressed on household wealth, women's schooling, and the interaction between both, controlling for relevant covariates. A similar model was used for the prevalence of double-burden pairs (stunted child with an overweight mother). In mothers with less than primary school, a doubling in wealth was not associated with improved child's height but was associated with an increase in mother's weight (3.7%, P effectively mitigated the negative effects of household wealth on the prevalence of double-burden households in rural Mexico. Where maternal schooling is low, poverty reduction must be accompanied by effective behavior change communication to prevent child stunting and to protect women from unhealthy weight gain.

  11. Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks

    DEFF Research Database (Denmark)

    Poulsen, Maria; Lukas, Claudia; Lukas, Jiri

    2012-01-01

    Nonproteolytic ubiquitylation of chromatin surrounding deoxyribonucleic acid double-strand breaks (DSBs), mediated by the RNF8/RNF168 ubiquitin ligases, plays a key role in recruiting repair factors, including 53BP1 and BRCA1, to reestablish genome integrity. In this paper, we show that human RNF......169, an uncharacterized E3 ubiquitin ligase paralogous to RNF168, accumulated in DSB repair foci through recognition of RNF168-catalyzed ubiquitylation products by its motif interacting with ubiquitin domain. Unexpectedly, RNF169 was dispensable for chromatin ubiquitylation and ubiquitin...... chromatin, RNF169 stimulated homologous recombination and restrained nonhomologous end joining, affecting cell survival after DSB infliction. Our results show that RNF169 functions in a noncanonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing...

  12. Regulation of TCR delta and alpha repertoires by local and long-distance control of variable gene segment chromatin structure.

    Science.gov (United States)

    Hawwari, Abbas; Krangel, Michael S

    2005-08-15

    Murine Tcrd and Tcra gene segments reside in a single genetic locus and undergo recombination in CD4- CD8- (double negative [DN]) and CD4+ CD8+ (double positive [DP]) thymocytes, respectively. TcraTcrd locus variable gene segments are subject to complex regulation. Only a small subset of approximately 100 variable gene segments contributes substantially to the adult TCRdelta repertoire. Moreover, although most contribute to the TCRalpha repertoire, variable gene segments that are Jalpha proximal are preferentially used during primary Tcra recombination. We investigate the role of local chromatin accessibility in determining the developmental pattern of TcraTcrd locus variable gene segment recombination. We find variable gene segments to be heterogeneous with respect to acetylation of histones H3 and H4. Those that dominate the adult TCRdelta repertoire are hyperacetylated in DN thymocytes, independent of their position in the locus. Moreover, proximal variable gene segments show dramatic increases in histone acetylation and germline transcription in DP thymocytes, a result of super long-distance regulation by the Tcra enhancer. Our results imply that differences in chromatin accessibility contribute to biases in TcraTcrd locus variable gene segment recombination in DN and DP thymocytes and extend the distance over which the Tcra enhancer can regulate chromatin structure to a remarkable 525 kb.

  13. The orphan adapter protein SLY1 as a novel anti-apoptotic protein required for thymocyte development

    Directory of Open Access Journals (Sweden)

    Beer-Hammer Sandra

    2009-07-01

    Full Text Available Abstract Background SH3 containing Lymphocyte Protein (SLY1 is a putative adapter protein exclusively expressed in lymphocytes which is involved in antigen receptor induced activation. We previously have generated SLY1Δ/Δ mice harbouring a partial deletion in the N-terminal region of SLY1 which revealed profound immunological defects in T and B cell functions. Results In this study, T cell development in SLY1-/- and SLY1Δ/Δ mice was analysed ex vivo and upon cultivation with the bone marrow stromal cell line OP9. SLY1-deficient thymocytes were compromised in inducing nutrient receptor expression and ribosomal protein S6 phosphorylation, indicating a defect in mTOR complex activation. Furthermore, SLY1 was identified as a novel anti-apoptotic protein required for developmental progression of T cell precursors to the CD4+CD8+ double-positive stage by protecting from premature programmed cell death initiation in developing CD4-CD8- double-negative thymocytes. In addition, SLY1 phosphorylation was differentially regulated upon Notch ligand-mediated stimulation and expression of the preTCR. Conclusion Thus, our results suggest a non-redundant role for SLY1 in integrating signals from both receptors in early T cell progenitors in the thymus.

  14. The effect of regular aerobic exercise on both positive and negative symptoms of male patients with chronic Schizophrenia: A double blinded study

    Directory of Open Access Journals (Sweden)

    Hossein Namdar areshtanab

    2016-11-01

    Full Text Available Nowadays in different communities, sport is being used as a mean to prevent diseases, improve health and have a sense of well-being. The evidences show that sport improves mental health, self-confidence, cognitive performance and on the other hand it decreases anxiety and depression. Therefore, this study aims to investigate the effect of regular aerobic exercise on both positive and negative symptoms of male patients with chronic Schizophrenia who are hospitalized at RAZI Psychiatric hospital, TABRIZ, IRAN. The present study, which has been done on 68 male patients with chronic Schizophrenia, is a double-blinded clinical trial study. Randomly chosen samples have been categorized in two groups of case(34 patients and control (34 patients. The case group samples participated in the designed exercise program during 24sessions over 8 weeks, 11hours in total. The positive and negative symptoms for both groups were assessed in two steps before starting the exercise program and also after that through Standard Anderson Positive and Negative questionnaire (SAPS.SANS. The data of both groups were compared using statistical tests, T-test, paired t-test , and Chi-square test. The results demonstrated that there is no significant relationship between before intervention in terms of positive and negative symptoms of disease (P>0.05. Furthermore, the results indicated that there is a significant statistical difference between the average total score of positive and negative symptoms of the disease in both case and control group after intervention (P<0.05.Health system officials and managers can implement programs and solutions for creating regular aerobic exercises for patients with Schizophrenia in order to reduce disease symptoms and improve the rate of recovery in patients with chronic mental disorders.

  15. Randomized Double-blinded and Controlled Clinical Trial on Treatment of HIV/AIDS by Zhongyan-4 (中研-4号)

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To assess the efficacy and safety of Zhongyan-4 (中研-4号, ZY-4, a Chinese herbal preparation worked out according to the therapeutic principle of supplementing qi, nourishing Yin,clearing heat and detoxication) in treating HIV/AIDS patients in the early or middle stage. Methods: Adopted was randomized double-blinded and placebo-parallel-controlled method, with 72 HIV/AIDS patients randomly divided into the ZY-4 group (36 patients) treated with ZY-4 and the control group (36 patients) treated with placebo. The treatment course was six months. The index of CD4+ , CD8+ counts, body weight, clinical symptom scoring were estimated at 4 time points (0, 1, 3 and 6 month in the course), and also the viral load before and after treatment. The whole course of observation was completed in 63 patients, 30 in the ZY-4group and 33 in the control group. Results: CD4 + count in the ZY-4 group got elevated by 7.70 ± 150.96/mm3on average, while that in the control group lowered by 27.33±85.28 /mm3. Fifteen out of the 30 patients in the ZY-4 group had their CD4+ count increased, which was evidently much higher than that in the control group (8/33, P<0.05), suggesting that the efficacy of ZY-4 is superior to that of placebo in elevating CD4 +count. Moreover, ZY-4 showed actions in elevating CD45RA+ and CD8+ count, reducing HIV virus load, improving clinical symptom/sign and increasing body weight of patients. No obvious adverse reaction was found in the clinical trial. Conclusion: ZY-4 has an immunity-protective and/or rebuilding function in HIV/AIDS patients in the early and middle stage, and also shows effects in lowering viral load, increasing body weight and improving symptoms and signs to a certain degree.

  16. Increased sensitivity of BRCA defective triple negative breast tumors to plumbagin through induction of DNA Double Strand Breaks (DSB).

    Science.gov (United States)

    Nair, Rakesh Sathish; Kumar, Jerald Mahesh; Jose, Jedy; Somasundaram, Veena; Hemalatha, Sreelatha K; Sengodan, Satheesh Kumar; Nadhan, Revathy; Anilkumar, Thapasimuthu V; Srinivas, Priya

    2016-05-25

    We have earlier shown that Plumbagin (PB) can induce selective cytotoxicity to BRCA1 defective ovarian cancer cells; however, the effect of this molecule in BRCA1 mutated breast cancers has not been analyzed yet. Here, we report that reactive oxygen species (ROS) induced by PB resulted in DNA DSB and activates downstream signaling by ATR/ATM kinases and subsequent apoptosis. PB reduces DNA- dependent protein kinase (DNA-PK) expression and inhibits NHEJ (Non Homologous End Joining) activity in BRCA1 defective breast cancer cells. Also, PB induces apoptosis in two different BRCA1 conditional knock out murine models: MMTV-Cre; BRCA1(Co/Co) and WAP-Cre; BRCA1(Co/Co), at 2 mg/kg body weight, but 32 mg/kg of carboplatin (CN) was needed to induce apoptosis in them. This is the first study where two different tissue specific promoter driven transgenic mice models with BRCA1 exon 11 deletions are used for preclinical drug testing. The apoptosis induced by PB in HR (Homologous Recombination) defective triple negative BRCA1 mutant cell lines and in mouse models occur by inducing ROS mediated DNA DSB. The toxicity profile as compared with CN in transgenic mice provides evidence for PB's safer disposition as a therapeutic lead in breast cancer drug development.

  17. Double attention bias for positive and negative emotional faces in clinical depression: evidence from an eye-tracking study.

    Science.gov (United States)

    Duque, Almudena; Vázquez, Carmelo

    2015-03-01

    According to cognitive models, attentional biases in depression play key roles in the onset and subsequent maintenance of the disorder. The present study examines the processing of emotional facial expressions (happy, angry, and sad) in depressed and non-depressed adults. Sixteen unmedicated patients with Major Depressive Disorder (MDD) and 34 never-depressed controls (ND) completed an eye-tracking task to assess different components of visual attention (orienting attention and maintenance of attention) in the processing of emotional faces. Compared to ND, participants with MDD showed a negative attentional bias in attentional maintenance indices (i.e. first fixation duration and total fixation time) for sad faces. This attentional bias was positively associated with the severity of depressive symptoms. Furthermore, the MDD group spent a marginally less amount of time viewing happy faces compared with the ND group. No differences were found between the groups with respect to angry faces and orienting attention indices. The current study is limited by its cross-sectional design. These results support the notion that attentional biases in depression are specific to depression-related information and that they operate in later stages in the deployment of attention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Double impact: what sibling data can tell us about the long-term negative effects of parental divorce.

    Science.gov (United States)

    Wolfinger, Nicholas H; Kowaleski-Jones, Lori; Smith, Ken R

    2003-01-01

    Most prior research on the adverse consequences of parental divorce has analyzed only one child per family. As a result, it is not known whether the same divorce affects siblings differently. We address this issue by analyzing paired sibling data from the 1994 General Social Survey (GSS) and 1994 Survey of American Families (SAF). Both seemingly unrelated regressions and random effects models are used to study the effect of family background on offspring's educational attainment and marital stability. Parental divorce adversely affects the educational attainment and the probability of divorce of both children within a sibship; in other words, siblings tend to experience the same divorce the same way. However, family structure of origin only accounts for a trivial portion of the shared variance in offspring's educational attainment and marital stability, so parental divorce is only one of many factors determining how offspring fare. These findings were unchanged when controlling for a number of differences both between and within sibships. Also, the negative effects of parental divorce largely do not vary according to respondent characteristics.

  19. Study of double bond equivalents and the numbers of carbon and oxygen atom distribution of dissolved organic matter with negative-mode FT-ICR MS.

    Science.gov (United States)

    Bae, EunJung; Yeo, In Joon; Jeong, Byungkwan; Shin, Yongsik; Shin, Kyung-Hoon; Kim, Sunghwan

    2011-06-01

    A strong linear relationship was observed between the average double bond equivalence (DBE) and the ratio of carbon to oxygen atoms in oxygenated compounds of dissolved organic matter (DOM). Data were acquired by a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS), equipped with a negative-mode electrospray ionization source. The slope and y-intercepts extracted from the linear relationship can be used to compare DOM samples originating from different locations. Significant differences in these parameters were observed between inland riverine and offshore coastal DOM samples. Offshore coastal DOM molecules underwent a change of one DBE for each removal or addition of two oxygen atoms. This suggested the existence of multiple carboxyl groups, each of which contains a double bond and two oxygen atoms. Inland riverine samples exhibited a change of ~1.5 DBE following the addition or removal of two oxygen atoms. This extra change in DBE was attributed to cyclic structures or unsaturated chemical bonds. The DBE value with maximum relative abundance and the minimum DBE value for each class of oxygenated compounds showed that approximately two oxygen atoms contributed to a unity change in DBE. The qualitative analyses given here are in a good agreement with results obtained from analyses using orthogonal analytical techniques. This study demonstrates that DBE and the carbon number distribution, observed by high resolution mass spectrometry, can be valuable in elucidating and comparing structural features of oxygenated molecules of DOM.

  20. Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ranran Zhang; Dongchu Ma; Xiaodong Xie; Wanqing Xie Co-first author; Tao Han; Yongye Liu; Zhaozhe Liu; Fang Guo; Yaling Han; Zhenyu Ding; Yinghui Sun

    2015-01-01

    Objective The aim of the present study was to investigate the ef ect of dendritic cel (DC)/cytokine-in-duced kil er cel (CIK) immunobiological cancer therapy in patients with triple-negative breast cancer (TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrol ed in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, dif erences between the two groups with regard to quality of life (QoL), immunological indicators (CD3, CD4, CD8, and NK cel levels), disease-free survival (DFS), and side ef ects of chemotherapy and DC/CIK treatment were evaluated. Results In the DC/CIK group, the proportion of NK cel s and CD3+ and CD4+ T-cel subgroups significantly increased, and the proportion of CD8+ cel s decreased when they were compared before and after DC/CIK therapy (P Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the con-trol group, and was not associated with any obvious side ef ects. Therefore, DC/CIK therapy is a safe and ef ective method for the treatment of TNBC.

  1. Double negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells

    Science.gov (United States)

    Yang, Xiaojun; Lin, Xiaojuan; Zhong, Xiaomin; Kaur, Sippy; Li, Ning; Liang, Shun; Lassus, Heini; Wang, Liping; Katsaros, Dionyssios; Montone, Kathleen; Zhao, Xia; Zhang, Youcheng; Bützow, Ralf; Coukos, George; Zhang, Lin

    2010-01-01

    A relatively rare aldehyde dehydrogenase 1 (ALDH1) positive “stem cell-like” subpopulation of tumor cells has the unique ability to initiate and perpetuate tumor growth; moreover it is highly resistant to chemotherapy and significantly associated with poor clinical outcomes. The development of more effective therapies for cancer requires targeting of this cell population. Using cDNA microarray analysis, we identified that the expression of the C. elegans lin-28 homolog (LIN28) was positively correlated with the percentage of ALDH1+ tumor cells; this was further validated in an independent set of tissue arrays (n=197). Both lose-of-function and gain-of-function studies demonstrated that LIN28 plays a critical role in the maintenance of ALDH1+ tumor cells. In addition, we found that there is a double negative feedback loop between LIN28 and let-7 in tumor cells, and that let-7 negatively regulates ALDH1+ tumor cells. Finally, we report that a LIN28/let-7 loop modulates self renewal and differentiation of mammary gland epithelial progenitor cells. Our data provide evidence that cancer stem cells may arise through a “reprogramming-like” mechanism. A rebalancing of the LIN28/let-7 regulatory loop could be a novel therapeutic strategy to target ALDH1+ cancer stem cells. PMID:21045151

  2. Human Lymph Node-Derived Fibroblastic and Double-Negative Reticular Cells Alter Their Chemokines and Cytokines Expression Profile Following Inflammatory Stimuli

    Science.gov (United States)

    Severino, Patricia; Palomino, Diana Torres; Alvarenga, Heliene; Almeida, Camila Bononi; Pasqualim, Denise Cunha; Cury, Adriano; Salvalaggio, Paolo Rogério; De Vasconcelos Macedo, Antonio Luiz; Andrade, Maria Claudina; Aloia, Thiago; Bromberg, Silvio; Rizzo, Luiz Vicente; Rocha, Fernanda Agostini; Marti, Luciana C.

    2017-01-01

    Lymph node (LN) is a secondary lymphoid organ with highly organized and compartmentalized structure. LNs harbor B, T, and other cells among fibroblastic reticular cells (FRCs). FRCs are characterized by both podoplanin (PDPN/gp38) expression and by the lack of CD31 expression. FRCs are involved in several immune response processes but mechanisms underlying their function are still under investigation. Double-negative cells (DNCs), another cell population within LNs, are even less understood. They do not express PDPN or CD31, their localization within the LN is unknown, and their phenotype and function remain to be elucidated. This study evaluates the gene expression and cytokines and chemokines profile of human LN-derived FRCs and DNCs during homeostasis and following inflammatory stimuli. Cytokines and chemokines secreted by human FRCs and DNCs partially diverged from those identified in murine models that used similar stimulation. Cytokine and chemokine secretion and their receptors expression levels differed between stimulated DNCs and FRCs, with FRCs expressing a broader range of chemokines. Additionally, dendritic cells demonstrated increased migration toward FRCs, possibly due to chemokine-induced chemotaxis since migration was significantly decreased upon neutralization of secreted CCL2 and CCL20. Our study contributes to the understanding of the biology and functions of FRCs and DNCs and, accordingly, of the mechanisms involving them in immune cells activation and migration. PMID:28261205

  3. Dominant negative mutant of Plasmodium Rad51 causes reduced parasite burden in host by abrogating DNA double-strand break repair.

    Science.gov (United States)

    Roy, Nabamita; Bhattacharyya, Sunanda; Chakrabarty, Swati; Laskar, Shyamasree; Babu, Somepalli Mastan; Bhattacharyya, Mrinal Kanti

    2014-10-01

    Malaria parasites survive through repairing a plethora of DNA double-stranded breaks (DSBs) experienced during their asexual growth. In Plasmodium Rad51 mediated homologous recombination (HR) mechanism and homology-independent alternative end-joining mechanism have been identified. Here we address whether loss of HR activity can be compensated by other DSB repair mechanisms. Creating a transgenic Plasmodium line defective in HR function, we demonstrate that HR is the most important DSB repair pathway in malarial parasite. Using mouse malaria model we have characterized the dominant negative effect of PfRad51(K143R) mutant on Plasmodium DSB repair and host-parasite interaction. Our work illustrates that Plasmodium berghei harbouring the mutant protein (PfRad51(K143R)) failed to repair DSBs as evidenced by hypersensitivity to DNA-damaging agent. Mice infected with mutant parasites lived significantly longer with markedly reduced parasite burden. To better understand the effect of mutant PfRad51(K143R) on HR, we used yeast as a surrogate model and established that the presence of PfRad51(K143R) completely inhibited DNA repair, gene conversion and gene targeting. Biochemical experiment confirmed that very low level of mutant protein was sufficient for complete disruption of wild-type PfRad51 activity. Hence our work provides evidence that HR pathway of Plasmodium could be efficiently targeted to curb malaria.

  4. A Double Negative Loop Comprising ETV6/RUNX1 and MIR181A1 Contributes to Differentiation Block in t(12;21-Positive Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Yung-Li Yang

    Full Text Available Childhood acute lymphoblastic leukemia (ALL with t(12;21, which results in expression of the ETV6/RUNX1 fusion gene, is the most common chromosomal lesion in precursor-B (pre-B ALL. We identified 17 microRNAs that were downregulated in ETV6/RUNX1+ compared with ETV6/RUNX1- clinical samples. Among these microRNAs, miR-181a-1 was the most significantly reduced (by ~75%; P < 0.001. Using chromatin immunoprecipitation, we demonstrated that ETV6/RUNX1 directly binds the regulatory region of MIR181A1, and knockdown of ETV6/RUNX1 increased miR-181a-1 level. We further showed that miR-181a (functional counterpart of miR-181a-1 could target ETV6/RUNX1 and cause a reduction in the level of the oncoprotein ETV6/RUNX1, cell growth arrest, an increase in apoptosis, and induction of cell differentiation in ETV6/RUNX1+ cell line. Moreover, ectopic expression of miR-181a also resulted in decreased CD10 hyperexpression in ETV6/RUNX1+ primary patient samples. Taken together, our results demonstrate that MIR181A1 and ETV6/RUNX1 regulate each other, and we propose that a double negative loop involving MIR181A1 and ETV6/RUNX1 may contribute to ETV6/RUNX1-driven arrest of differentiation in pre-B ALL.

  5. Double-negative feedback between S-phase cyclin-CDK and CKI generates abruptness in the G1/S switch

    Directory of Open Access Journals (Sweden)

    Rainis eVenta

    2012-12-01

    Full Text Available The G1/S transition is a crucial decision point in the cell cycle. At G1/S, there is an abrupt switch from a state of high CDK inhibitor (CKI levels and low S-phase CDK activity to a state of high S-phase CDK activity and degraded CKI. In budding yeast, this transition is triggered by phosphorylation of the Cdk1 inhibitor Sic1 at multiple sites by G1-phase CDK (Cln1,2-Cdk1 and S-phase CDK (Clb5,6-Cdk1 complexes. Using mathematical modeling we demonstrate that the mechanistic basis for the abruptness and irreversibility of the G1/S transition is the highly specific phosphorylation of Sic1 by S-phase CDK complex. This switch is generated by a double negative feedback loop in which S-CDK1 phosphorylates Sic1, thus targeting it for destruction, and thereby liberating further S-CDK1 from the inhibitory Sic1-S-CDK1 complex. Our model predicts that the abruptness of the switch depends upon a strong binding affinity within the Sic1-S-CDK inhibitory complex. In vitro phosphorylation analysis using purified yeast proteins revealed that free Clb5-Cdk1 can create positive feedback by phosphorylating Sic1 that is bound in the inhibitory complex, and that Sic1 inhibits Clb5-Cdk1 with a sub-nanomolar inhibition constant. Our model also predicts that if the G1-phase CDK complex is too efficient at targeting Sic1 for destruction, then G1/S becomes a smooth and readily reversible transition. We propose that the optimal role for the G1-phase CDK in the switch would not be to act as a kinase activity directly responsible for abrupt degradation of CKI, but rather to act as a priming signal that initiates a positive feedback loop driven by emerging free S-phase CDK.

  6. Double-stranded RNA-binding protein DRB3 negatively regulates anthocyanin biosynthesis by modulating PAP1 expression in Arabidopsis thaliana.

    Science.gov (United States)

    Sawano, Hikaru; Matsuzaki, Takuma; Usui, Tomoyuki; Tabara, Midori; Fukudome, Akihito; Kanaya, Akihiro; Tanoue, Daichi; Hiraguri, Akihiro; Horiguchi, Gorou; Ohtani, Misato; Demura, Taku; Kozaki, Toshinori; Ishii, Kazuo; Moriyama, Hiromitsu; Fukuhara, Toshiyuki

    2017-01-01

    The model plant Arabidopsis thaliana has five double-stranded RNA-binding proteins (DRB1-DRB5), two of which, DRB1 and DRB4, are well characterized. In contrast, the functions of DRB2, DRB3 and DRB5 have yet to be elucidated. In this study, we tried to uncover their functions using drb mutants and DRB-over-expressed lines. In over-expressed lines of all five DRB genes, the over-expression of DRB2 or DRB3 (DRB2ox or DRB3ox) conferred a downward-curled leaf phenotype, but the expression profiles of ten small RNAs were similar to that of the wild-type (WT) plant. Phenotypes were examined in response to abiotic stresses. Both DRB2ox and DRB3ox plants exhibited salt-tolerance. When these plants were exposed to cold stress, drb2 and drb3 over-accumulated anthocyanin but DRB2ox and DRB3ox did not. Therefore, the over-expression of DRB2 or DRB3 had pleiotropic effects on host plants. Microarray and deep-sequencing analyses indicated that several genes encoding key enzymes for anthocyanin biosynthesis, including chalcone synthase (CHS), dihydroflavonol reductase (DFR) and anthocyanidin synthase (ANS), were down-regulated in DRB3ox plants. When DRB3ox was crossed with the pap1-D line, which is an activation-tagged transgenic line that over-expresses the key transcription factor PAP1 (Production of anthocyanin pigmentation1) for anthocyanin biosynthesis, over-expression of DRB3 suppressed the expression of PAP1, CHS, DFR and ANS genes. DRB3 negatively regulates anthocyanin biosynthesis by modulating the level of PAP1 transcript. Since two different small RNAs regulate PAP1 gene expression, a possible function of DRB3 for small RNA biogenesis is discussed.

  7. The production of alpha/beta and gamma/delta double negative (DN) T-cells and their role in the maintenance of pregnancy.

    Science.gov (United States)

    Chapman, John C; Chapman, Fae M; Michael, Sandra D

    2015-07-12

    The ability of the thymus gland to convert bone marrow-derived progenitor cells into single positive (SP) T-cells is well known. In this review we present evidence that the thymus, in addition to producing SP T-cells, also has a pathway for the production of double negative (DN) T-cells. The existence of this pathway was noted during our examination of relevant literature to determine the cause of sex steroid-induced thymocyte loss. In conducting this search our objective was to answer the question of whether thymocyte loss is the end product of a typical interaction between the reproductive and immune systems, or evidence that the two systems are incompatible. We can now report that "thymocyte loss" is a normal process that occurs during the production of DN T-cells. The DN T-cell pathway is unique in that it is mediated by thymic mast cells, and becomes functional following puberty. Sex steroids initiate the development of the pathway by binding to an estrogen receptor alpha located in the outer membrane of the mast cells, causing their activation. This results in their uptake of extracellular calcium, and the production and subsequent release of histamine and serotonin. Lymphatic vessels, located in the subcapsular region of the thymus, respond to the two vasodilators by undergoing a substantial and preferential uptake of gamma/delta and alpha/beta DN T- cells. These T- cells exit the thymus via efferent lymphatic vessels and enter the lymphatic system.The DN pathway is responsible for the production of three subsets of gamma/delta DN T-cells and one subset of alpha/beta DN T-cells. In postpubertal animals approximately 35 % of total thymocytes exit the thymus as DN T-cells, regardless of sex. In pregnant females, their levels undergo a dramatic increase. Gamma/delta DN T-cells produce cytokines that are essential for the maintenance of pregnancy.

  8. 双重消减纯化体外培养许旺细胞%In vitro purification of Schwann cells with double negative selection

    Institute of Scientific and Technical Information of China (English)

    史金凤; 雷雳; 夏寅

    2007-01-01

    BACKGROUND: Although cultured technique and purified method of Schwann cells (SCs) are changed successively,purity is still limited. Whether double negative selections can culture high-purified SCs still needs a further study.OBJECTIVE: To investigate the effects of double negative selections on growth and purity of SCs.DESIGN: Controlled animal study.SETTING: Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University,and the Beijing Institution of Otolaryngology.MATERIALS: The experiment was carried out in the Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University and the Beijing Institution of Otolaryngology between May 2006 and July 2006. Twenty new-born Wistar rats of 3 days (without gender limitation) were provided by the Experimental Animal Center of the Chinese Medical Academy.METHODS: The sciatic nerves of rats were digested by 0.2% collagenase. ① Grouping: All the rats were divided into 4 groups with 5 each. The experimental group was depurated by differential adhesion and Ara-c for 30 minutes. SCs in the control group 1 and 2 were managed by differential adhesion and Ara-c for 30 minutes, respectively. Cells in the control group 3 were not purified. ② Evaluation: The cell growth was observed under invert microscope; growth curves were measured with MTT method in the experimental group and control group 3 to observe cell proliferation. In addition, the SCs were identified by immunocytochemistry; the culture purity was calculated (ratio of S100 positive cells in each sight).MAIN OUTCOME MEASURES: ① Growth of SCs; ② immunocytochemistry stain of SCs; ③ growth curve of SCs; ④ purity of SCs.RESULTS: ① Growth of SCs: At 5 days after incubation, the SCs proliferated well. SCs were spindle, bipolar and sometimes tripolar, with obvious nuclei and a little cytoplasm. There was more fibroblast cell in the group 3 than that in experimental group. ② Growth

  9. Negation and negative concord in romance

    NARCIS (Netherlands)

    Swart, Henriëtte de; Sag, I.A.

    This paper addresses the two interpretations a combination of negative indefinites can get in concord languages like French, namely a concord reading which amounts to a single negation, or a double negation reading. We develop an analysis in a polyadic framework, in which a sequence of

  10. Subpopulações de linfócitos CD4, CD8 e CD45RB em enxertos esplênicos autólogos heterotópicos de camundongos sadios e esquistossomóticos : estudo comparativo com o baço intacto e o remanescente esplênico vascularizado

    OpenAIRE

    Carlos Leitão Adeodato, Luís

    2004-01-01

    A esquistossomose mansônica é uma doença infecciosa, causada por um verme (Schistosoma mansoni) que no seu ciclo evolutivo pode ter o homem como um dos seus hospedeiros definitivos. Nas formas mais avançadas, a embolização maciça de ovos depositados por vermes adultos no sistema da veia porta para o parênquima hepático provoca alterações inflamatórias na estrutura do fígado, modificando a arquitetura do órgão e induzindo à formação de granulomas, cuja resolução causa a fibrose de ...

  11. Autoimmune lymphoproliferative disorder in an adult patient

    Directory of Open Access Journals (Sweden)

    N K Desai

    2011-01-01

    Full Text Available A 50-year-old male patient presented with fever, epistaxis and multiple lymphadenopathy since 15 days. In the light of the above presentation a complete workup was initiated to exclude common conditions like tuberculosis, acquired immunodeficiency syndrome, lymphoid malignancy and sarcoidosis. After excluding common conditions a biopsy of cervical lymph node demonstrated reactive lymphadenitis with paracortical hyperplasia. Immunohistochemistry demonstrated double negative lymphocytes (CD4-, CD8-. A diagnosis of autoimmune lymphoproliferative disorder syndrome (ALPS (probable was made and patient was started on 1 mg/kg of steroids. Patient showed a dramatic improvement with respect to general wellbeing, fever and regression of lymphadenopathy. This entity of ALPS has been recently identified and classified; most of the reports are from the pediatric population. To the best of our knowledge ours is one of the few cases of this entity being reported in an adult patient from India.

  12. A Novel and Likely Inherited Lymphoproliferative Disease in British Shorthair Kittens.

    Science.gov (United States)

    Aberdein, D; Munday, J S; Fairley, R A; Vernau, W; Thompson, K G

    2015-11-01

    An unusual lymphoproliferative disease was identified in multiple closely related British Shorthair (BSH) kittens, suggesting an inherited predisposition to disease. Affected kittens typically developed rapidly progressive and marked generalized lymphadenopathy, moderate splenomegaly, and regenerative and likely hemolytic anemia from 6 weeks of age. Microscopic findings were suggestive of multicentric T-cell lymphoma, but additional testing revealed a polyclonal population of CD3+/CD4-/CD8- "double negative" T cells (DNT cells). This is a novel disease presentation with similarities to the human disorder autoimmune lymphoproliferative syndrome (ALPS), a rare inherited disease causing lymphoproliferation and variable manifestations of autoimmunity. The human disease is most commonly due to the presence of Fas gene mutations causing defective lymphocyte apoptosis, and further investigations of both the mode of inheritance and genetic basis for disease in affected cats are currently in progress.

  13. Unexplained lymphadenopathies: autoimmune lymphoproliferative syndrome in an adult patient.

    Science.gov (United States)

    Leal-Seabra, Fatima; Costa, Gonçalo Sarmento; Coelho, Henrique Pereira; Oliveira, Agripino

    2016-12-15

    Autoimmune lymphoproliferative syndrome (ALPS) is characterised by massive enlargement of the lymphoid organs, autoimmune cytopenias and a predisposition to develop lymphoid malignancies. The basic defect is a disturbance of the lymphocyte apoptosis, and a high number of circulating TCRab CD3(+)CD4(-)CD8(-) T-cells (double-negative T cells (DNT cells)). We describe a case of a 41-year-old man with fever, hepatosplenomegaly, multiple lymphadenopathy, autoimmune haemolytic anaemia and severe thrombocytopenia. Peripheral blood immunophenotyping revealed elevation of the characteristic DNT cells in 8% and high levels of interleukin 10. Histopathological analysis of lymph nodes showed lymphadenitis with paracortical hyperplasia. It was assumed as a probable diagnosis of ALPS, and the procedure was to medicate the patient with steroids. As a result, a significant clinical improvement was achieved, and he has been in remission for 2 years. To our knowledge, this is the first case reported in a Portuguese adult patient.

  14. RasGRP1, but not RasGRP3, is required for efficient thymic β-selection and ERK activation downstream of CXCR4.

    Directory of Open Access Journals (Sweden)

    Dominic P Golec

    Full Text Available T cell development is a highly dynamic process that is driven by interactions between developing thymocytes and the thymic microenvironment. Upon entering the thymus, the earliest thymic progenitors, called CD4(-CD8(- 'double negative' (DN thymocytes, pass through a checkpoint termed "β-selection" before maturing into CD4(+CD8(+ 'double positive' (DP thymocytes. β-selection is an important developmental checkpoint during thymopoiesis where developing DN thymocytes that successfully express the pre-T cell receptor (TCR undergo extensive proliferation and differentiation towards the DP stage. Signals transduced through the pre-TCR, chemokine receptor CXCR4 and Notch are thought to drive β-selection. Additionally, it has long been known that ERK is activated during β-selection; however the pathways regulating ERK activation remain unknown. Here, we performed a detailed analysis of the β-selection events in mice lacking RasGRP1, RasGRP3 and RasGRP1 and 3. We report that RasGRP1 KO and RasGRP1/3 DKO deficient thymi show a partial developmental block at the early DN3 stage of development. Furthermore, DN3 thymocytes from RasGRP1 and RasGRP1/3 double knock-out thymi show significantly reduced proliferation, despite expression of the TCRβ chain. As a result of impaired β-selection, the pool of TCRβ(+ DN4 is significantly diminished, resulting in inefficient DN to DP development. Also, we report that RasGRP1 is required for ERK activation downstream of CXCR4 signaling, which we hypothesize represents a potential mechanism of RasGRP1 regulation of β-selection. Our results demonstrate that RasGRP1 is an important regulator of proliferation and differentiation at the β-selection checkpoint and functions downstream of CXCR4 to activate the Ras/MAPK pathway.

  15. Blood concentrations of hydroxychloroquine and its desethyl derivative correlate negatively with the percentage of CD45RO+ cells among CD4+ lymphocytes in hydroxychloroquine-treated lupus patients.

    Science.gov (United States)

    Sailler, Laurent; Puissant, Bénédicte; Méliani, Pascal; Castex, Jean Olivier; Saivin, Sylvie; Adoue, D; Fournie, B; Arlet, Philippe; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse; Pourrat, Jacques; Blancher, Antoine

    2007-06-01

    The objective of the study was to investigate the influence of the blood concentrations of hydroxychloroquine ([HCQ]) and its derivative desethylhydroxychloroquine ([DHCQ]) on lymphocyte activation or differentiation in HCQ-treated lupus patients. We studied the correlations between [HCQ], [DHCQ], and the frequency of various lymphocyte subsets in 58 HCQ-treated lupus patients (mean HCQ dose: 4.93 +/- 1.58 mg/kg/day; mean duration of the disease: 122 +/- 64 months). [HCQ] and [DHCQ] were determined by high-performance liquid chromatography (HPLC). Lymphocyte markers were studied by flow cytometry using monoclonal anti-CD3, -CD4, -CD8, -CD25, -DR, -CD45RA, -CD45RO, -CD19, -CD38, and -CD86 antibodies. sIL2-R serum concentrations were measured by enzyme-linked immunosorbent assay (ELISA). [HCQ] and [DHCQ] were 599.9 ng/mL (median: 529.5; range: 55-1935) and 353.43 (median: 286 ng/mL; range: 118-1090). In a multiple regression analysis, [HCQ] and [DHCQ] were associated with the HCQ prescribed dose in mg/kg/day (P = 0.0002 and P = 0.03) and with compliance to the treatment (P = 0.004 and P = 0.03). We found a negative correlation between [HCQ], [DHCQ], and the CD45RO+ cell frequency among CD3+CD4+ cells (P = 0.03 and P = 0.007, respectively). Other lymphocyte subset markers (LSMs) and sIL2-R concentrations were not significantly associated with [HCQ] or [DHCQ]. In the multiple regression analysis, CD45RO+ expression was negatively influenced by [HCQ] (P = 0.005), and positively influenced by smoking habits (P = 0.005) and age (P = 0.005). Similar results were found in the multivariate model including [DHCQ]. Disease activity and taking more than 10 mg/day of corticosteroids or an immunosuppressive drug did not influence CD45RO+ expression. Lupus patients had less CD3+CD4+CD45RO+ cells than controls (P = 0.03). In lupus patients, HCQ and DHCQ may alter the generation or the blood circulation of CD4+CD45RO+ lymphocytes in a concentration-dependent pattern.

  16. Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study.

    Science.gov (United States)

    Palm, Ulrich; Keeser, Daniel; Hasan, Alkomiet; Kupka, Michael J; Blautzik, Janusch; Sarubin, Nina; Kaymakanova, Filipa; Unger, Ina; Falkai, Peter; Meindl, Thomas; Ertl-Wagner, Birgit; Padberg, Frank

    2016-09-01

    Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (-36.1%) than after sham tDCS (-0.7%). PANSS sum scores decreased significantly more with active (-23.4%) than with sham stimulation (-2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Increased TCR signal strength in DN thymocytes promotes development of gut TCRαβ((+))CD8αα((+)) intraepithelial lymphocytes.

    Science.gov (United States)

    Grandjean, Capucine L; Sumaria, Nital; Martin, Stefania; Pennington, Daniel J

    2017-09-06

    CD4((+))CD8((+)) "double positive" (DP) thymocytes differentiate into diverse αβ T cell sub-types using mechanistically distinct programs. For example, conventional αβ T cells develop from DP cells after partial-agonist T cell receptor (TCR) interactions with self-peptide/MHC, whereas unconventional αβ T cells, such as TCRαβ((+))CD8αα((+)) intraepithelial lymphocytes (IELs), require full-agonist TCR interactions. Despite this, DP cells appear homogeneous, and it remains unclear how distinct TCR signalling instructs distinct developmental outcomes. Moreover, whether TCR signals at earlier stages of development, for example in CD4((-))CD8((-)) double negative (DN) cells, impact on later fate decisions is presently unknown. Here, we assess four strains of mice that display altered TCR signal strength in DN cells, which correlates with altered generation of unconventional TCRαβ((+))CD8αα((+)) IELs. FVB/n mice (compared to C57BL/6 animals) and mice with altered preTCRα (pTα) expression, both displayed weaker TCR signalling in DN cells, an inefficient DN-to-DP transition, and reduced contribution of TCRαβ((+))CD8αα((+)) IELs to gut epithelium. Conversely, TCRαβ((+))CD8αα((+)) IEL development was favoured in mice with increased TCR signal strength in DN cells. Collectively, these data suggest TCR signal strength in DN cells directly impacts on subsequent DP cell differentiation, fundamentally altering the potential of thymocyte progenitors to adopt conventional versus unconventional T cell fates.

  18. Efficacy of bilateral repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia : results of a multicenter double-blind randomized controlled trial

    NARCIS (Netherlands)

    Dlabac-de Lange, J. J.; Bais, L.; van Es, F. D.; Visser, B. G. J.; Reinink, E.; Bakker, B.; van den Heuvel, E. R.; Aleman, A.; Knegtering, H.

    2015-01-01

    Background. Few studies have investigated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for negative symptoms of schizophrenia, reporting inconsistent results. We aimed to investigate whether 10 Hz stimulation of the bilateral dorsolateral prefrontal cortex during 3 w

  19. Outpatient diagnosis and treatment of double negative seronegative spondyloarthropathy%双阴性血清阴性脊柱关节病的门诊诊治

    Institute of Scientific and Technical Information of China (English)

    陈睿; 宋恒平

    2014-01-01

    目的:探讨双阴性血清阴性脊柱关节病(Both Negative-Seronegtive Spondyloarthro Pathies BNSPA)的门诊诊治。方法20例具有SPA症状的患者HLA-B27检测全部报告阴性,骶髂关节影像学报告全部阴性,均按SPA的诊治思路做进一步检查治疗。结果经抗SPA治疗后,症状全部得以明显控制,无一例出现典型的骶髂关节影像学变化。结论国民体质的提高,早期抗SPA的干预是HLA-B27阴性频率较高的一个重要因素,而骶髂关节炎影像学的误判也是SIJ阳性率不高的一个重要原因。根据临床征象以BNSPA诊治,取得良好效果。%Objective To explore the diagnosis and treatment of outpatients of both negative-seronegative spondyloarthropathy ( BNSPA ). Methods 20 patients who had the symptoms of SPA with negative test report of HLA-B27 and sacroiliac joint imaging,received the further examination and treatment as SPA. Results After anti-SPA treatment,all the patients' symptoms were signifi-cantly controlled,no typical imaging changes of sacroiliac joint appeared. Conclusion The early in-tervention against SPA is an important reason of negative HLA-B27,and the misjudgment of sacroil-iac joint imaging can cause negative HLA-B27 too. Treatment based on clinical manifestations of BNSPA achieved good results.

  20. Comparison between the AA/EPA ratio in depressed and non depressed elderly females: omega-3 fatty acid supplementation correlates with improved symptoms but does not change immunological parameters

    Directory of Open Access Journals (Sweden)

    Rizzo Angela

    2012-10-01

    Full Text Available Abstract Background Depression is one of the most frequently missed diagnoses in elderly people, with obvious negative effects on quality of life. Various studies have shown that long chain omega-3 polyunsaturated fatty acids (n-3 PUFA may be useful in its management. Our objective was to evaluate whether a supplement containing n-3 PUFA improves depressive symptoms in depressed elderly patients, and whether the blood fatty acid pattern is correlated with these changes. Methods The severity of depressive symptoms according to the Geriatric Depression Scale (GDS, blood fatty acid composition and erythrocyte phospholipids were analyzed in 46 depressed females aged 66-95y, diagnosed with depression according to DSMIV, within the context of a randomized, double-blind, placebo-controlled trial. 22 depressed females were included in the intervention group (2.5 g/day of n-3 PUFA for 8 weeks, and 24 in the placebo group. We also measured immunological parameters (CD2, CD3, CD4, CD8, CD16, CD19 and cytokines (IL-5, IL-15. Results The mean GDS score and AA/EPA ratio, in whole blood and RBC membrane phospholipids, were significantly lower after 2 months supplementation with n-3 PUFA. A significant correlation between the amelioration of GDS and the AA/EPA ratio with some immunological parameters, such as CD2, CD19, CD4, CD16 and the ratio CD4/CD8, was also found. Nevertheless, omega-3 supplementation did not significantly improve the studied immunological functions. Conclusions n-3 PUFA supplementation ameliorates symptoms in elderly depression. The n-3 PUFA status may be monitored by means of the determination of whole blood AA/EPA ratio.

  1. Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Mulligan, Kathleen; Glidden, David V.; Anderson, Peter L.; Liu, Albert; McMahan, Vanessa; Gonzales, Pedro; Ramirez-Cardich, Maria Esther; Namwongprom, Sirianong; Chodacki, Piotr; de Mendonca, Laura Maria Carvalo; Wang, Furong; Lama, Javier R.; Chariyalertsak, Suwat; Guanira, Juan Vicente; Buchbinder, Susan; Bekker, Linda-Gail; Schechter, Mauro; Veloso, Valdilea G.; Grant, Robert M.; Vargas, Lorena; Sanchez, Jorge; Mai, Chiang; Saokhieo, Pongpun; Murphy, Kerry; Gilmore, Hailey; Holland, Sally; Faber, Elizabeth; Duda, John; Bewerunge, Linda; Batist, Elizabeth; Hoskin, Christine; Brown, Ben; de Janeiro, Rio; Beppu-Yoshida, Carina; da Costa, Marcellus Dias; Assis de Jesus, Sergio Carlos; Grangeiro da Silva, Jose Roberto; Millan, Roberta; de Siqueira Hoagland, Brenda Regina; Martinez Fernandes, Nilo; da Silva Freitas, Lucilene; Grinsztejn, Beatriz; Pilotto, Jose; Bushman, Lane; Zheng, Jia-Hua; Anthony Guida, Louis; Kline, Brandon; Goicochea, Pedro; Manzo, Jonathan; Hance, Robert; McConnell, Jeff; Defechereux, Patricia; Levy, Vivian; Robles, Malu; Postle, Brian; Burns, David; Rooney, James

    2015-01-01

    Background. Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. Methods. Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. Results. In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, −0.91% [95% confidence interval {CI}, −1.44% to −.38%]; P = .001) and hip (−0.61% [95% CI, −.96% to −.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged −1.42% ± 29% and −0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD. Conclusions. In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. Clinical Trials Registration. NCT00458393. PMID:25908682

  2. Improvement of drain current of AlGaN/GaN-HEMT through the modification of negative differential conductance (NDC), current collapse, self-heating and optimization of double hetero structure

    Science.gov (United States)

    Basumatary, Bikramjit; Maity, Santanu; Muchahary, Deboraj

    2016-09-01

    For the high-power application, high breakdown voltage of the HEMT device is required that is free from the negative effects such as current collapse and NDC. In this paper, it is found that without any substrate for the higher dimension, the breakdown is larger than the lower dimension. However, it is not free from NDC, which can be eliminated by the shorter channel. Back barrier layer is used to increase this breakdown voltage for the shorter dimension which has given very efficient result, doubling the voltage from 6 V to 13 V for the 'x' composition of 0.3 of AlxGa1-xN and 16 V for AlN back barrier. At the end, the relation of capacitance to the breakdown voltage for the shorter channel is derived, which shows that the breakdown voltage is mostly dependent on the carrier concentration in the lower layer.

  3. The Effects of Negative Differential Resistance, Bipolar Spin-Filtering, and Spin-Rectifying on Step-Like Zigzag Graphene Nanoribbons Heterojunctions with Single or Double Edge-Saturated Hydrogen

    Science.gov (United States)

    Wang, Lihua; Zhao, Jianguo; Ding, Bingjun; Guo, Yong

    2016-09-01

    In this study, we investigated the spin-resolved transport aspects of step-like zigzag graphene ribbons (ZGNRs) with single or double edge-saturated hydrogen using a method that combined the density functional theory with the nonequilibrium Green's function method under the local spin density approximation. We found that, when the ZGNR-based heterojunctions were in a parallel or antiparallel layout, negative differential resistance, the maximum bipolar spin-filtering, and spin-rectifying effects occurred synchronously except for the case of spin-down electrons in the parallel magnetic layouts. Interestingly, these spin-resolved transport properties were almost unaffected by altering the widths of the two component ribbons. Therefore, step-like ZGNR heterojunctions are promising for use in designing high-performance multifunctional spintronic devices.

  4. The Effects of Negative Differential Resistance, Bipolar Spin-Filtering, and Spin-Rectifying on Step-Like Zigzag Graphene Nanoribbons Heterojunctions with Single or Double Edge-Saturated Hydrogen

    Science.gov (United States)

    Wang, Lihua; Zhao, Jianguo; Ding, Bingjun; Guo, Yong

    2017-01-01

    In this study, we investigated the spin-resolved transport aspects of step-like zigzag graphene ribbons (ZGNRs) with single or double edge-saturated hydrogen using a method that combined the density functional theory with the nonequilibrium Green's function method under the local spin density approximation. We found that, when the ZGNR-based heterojunctions were in a parallel or antiparallel layout, negative differential resistance, the maximum bipolar spin-filtering, and spin-rectifying effects occurred synchronously except for the case of spin-down electrons in the parallel magnetic layouts. Interestingly, these spin-resolved transport properties were almost unaffected by altering the widths of the two component ribbons. Therefore, step-like ZGNR heterojunctions are promising for use in designing high-performance multifunctional spintronic devices.

  5. Research on the Negative Effects and Countermeasures of Double Surplus in China's International Balance of Payments%我国国际收支双顺差的负面效应及对策研究

    Institute of Scientific and Technical Information of China (English)

    余小雨

    2012-01-01

      Since 1994, China's international balance of payments has remained in double surplus and China has become the superpower of foreign exchange reserves, which has increased the difficulty of its foreign exchange management and the pressure of RMB appreciation. In addition, this situation has brought some negative effects on the effectiveness of its monetary policy and worsened the relationship between China and its trade partners. Based on detailed analysis of the negative effects of double surplus in China's international balance of payments to⁃wards its economy, this paper puts forward some countermeasures to improve the situation of its international trade surplus.%  从1994年至今,我国的国际收支双顺差的局面长期存在,这种局面带动了我国外汇储备的剧增,使得我国成为外汇储备第一大国,也使得我国的外汇管理难度增加,人民币升值压力增大,对货币政策的有效性产生负面影响,造成我国和贸易伙伴国之间的关系恶化。文章分析国际收支双顺差的长期存在对我国经济产生的负面效用,针对这些负面影响提出改善我国国际收支双顺差的相关对策。

  6. Add-on Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-week, randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Kardashev, Adasa; Ratner, Yael; Ritsner, Michael S

    2015-07-28

    Pregnenolone (PREG) and L-Theanine (LT) have shown ameliorative effects on various schizophrenia symptoms. This is the first study to evaluate the efficacy and safety of augmentation of antipsychotic treatment among patients with chronic schizophrenia or schizoaffective disorder with PREG - LT. Double-blind, placebo-controlled trial of PREG - LT or placebo augmentation was conducted for 8 weeks with 40 chronic DSM-IV schizophrenia and schizoaffective disorder patients with suboptimal response to antipsychotics. Oral PREG (50 mg/day) with LT (400 mg/day) or placebo were added to a stable regimen of antipsychotic medication from March 2011 to October 2013. The participants were rated using the Scale for the Assessment of Negative Symptoms (SANS), Hamilton Scale for Anxiety (HAM-A), and Positive and Negative Syndrome Scale (PANSS) scales bi-weekly. The decrease of SANS and HAM-A scores were the co-primary outcomes. Secondary outcomes included assessments of general functioning and side effects. Negative symptoms such as blunted affect, alogia, and anhedonia (SANS) were found to be significantly improved, with moderate effect sizes among patients who received PREG-LT, in comparison with the placebo group. Add-on PREG-LT also significantly associated with a reduction of anxiety scores such as anxious mood, tension, and cardiovascular symptoms (HAM-A), and elevation of general functioning (GAF). Positive symptoms, antipsychotic agents, concomitant drugs, and illness duration did not associate significantly with effect of PREG-LT augmentation. PREG-LT was well-tolerated. Pregnenolone with L-Theanine augmentation may offer a new therapeutic strategy for treatment of negative and anxiety symptoms in schizophrenia and schizoaffective disorder. Further studies are warranted. clinicaltrials.gov Identifier: NCT01831986.

  7. Analysis of negative sequence and efficiency of balance transformer connected in Y and double trapezoids%星形-双梯形接线平衡变压器负序及效率分析

    Institute of Scientific and Technical Information of China (English)

    刘谋君; 罗隆福; 张志文; 宁志豪; 黄际元

    2012-01-01

    由于现有电气化铁道牵引负荷的不对称性,导致电力系统含有大量负序电流,牵引变压器运行效率不高.为了解决上述问题,对星形-双梯形接线三相变两相平衡变压器进行了研究,重点分析其负序特性及效率特性,并在不同负载工况下,探讨一次侧电流不平衡度及变压器运行效率的情况,得出了电流不平衡度为零且变压器运行效率最高的条件.通过MATLAB建模对其负序特性与效率特性进行了仿真研究,结果表明该变压器能抑制负序电流的产生.%The unbalanced load of electrified railway causes big negative sequence currents,resulting in low efficiency of traction transformer. The three-phase to two-phase balance transformer connected in Y and double trapezoids is researched and its characteristics of negative-sequence and efficiency are analyzed. The unbalance degree of the current at primary side and the operating efficiency of transformer are studied under different loads,and the conditions to achieve zero current unbalance degree with highest transformer efficiency are obtained. Simulative study is carried out with MATLAB and results show that the transformer suppresses the negative sequence current effectively.

  8. Doppelt negative T-Lymphozyten, löslicher FAS Rezeptor und löslicher FAS Ligand bei Kindern mit häufigen Infektionen

    OpenAIRE

    Renner, Christian

    2004-01-01

    Es wurden 29 Patienten untersucht, die sich wegen häufigen Infektionen im Dr. von Haunerschen Kinderspital vorstellten. Hierbei wurde die prozentuale Verteilung von CD4-, CD8-positiven und doppelt negativen T-Lymphozyten bestimmt. Ebenfalls bestimmt wurden die Plasmaspiegel der Plasmaproteine sFas und sFasL. Der prozentuale Anteil an DN-T-Zellen lag signifikant über dem der gesunden Kontrollen bei gleichzeitig erniedrigten CD8 positiven Zellen. Es wird angenommen, dass aktivierte T-Lymphoz...

  9. 类获得性免疫缺陷(阴性HIV)“患者”的流行病学调查%Epidemiological investigation of cases with complained AIDS-related complex (HIV negative)

    Institute of Scientific and Technical Information of China (English)

    刘雅琼; 林辉; 于磊; 王清青; 王太武; 马翔宇; 凌华; 吴国辉; 张路

    2013-01-01

    目的 对社区类获得性免疫缺陷(AIDS)综合征(阴性HIV)“患者”进行病因探索.方法 采用定性系统分析筛检国内外相关综合征报道病例,探索类AIDS综合征“患者”临床特征可能的聚类属性;通过现况调查掌握“患者”人群的一般特征和临床特征.结果 定性系统分析显示,目前在世界范围,与类AIDS综合征(阴性HIV)“患者”相似的疾病有2种,即CD4+T淋巴细胞缺陷综合征(ICL)和非结核分枝杆菌感染(NTM感染);通过174例网络调查和52例现场观察,发现“患者”人群以男性为主,青、中年为主;在国内分布地区广泛;主诉症状涉及呼吸道、消化道、皮肤、肌肉、骨骼和神经系统;根据症状特点,病程有急性期和稳定期之分;群体症状及体征为:淋巴结部位肿胀感、骨痛、肌肉“跳”(痛)、淋巴结节、皮肤结节(皮疹)、舌苔白厚、关节弹响、皮肤干燥;52例“患者”检测发现CD4+T淋巴细胞< 500/μL 17例(32.69%)、CD4/CD8比值异常16例(30.77%)、干扰素-γ抗体阳性17例(36.69%)和PPD阳性39例(++~+++,75.00%);高危险性行为是可疑的暴露因素之一.结论 类AIDS综合征(阴性HIV)“患者”现象不能完全用心理因素予以解释,其呈现的临床特征有明显的一致性和规律性,亟待开展深入研究进行分析.%Objective To investigate the possible causes of AIDS-related complex (HIV negative) in community population. Methods Qualitative systematic analysis was used to screen the cases with AIDS-related complex (HIV negative) that had been reported. The possible clustering types of the clinical features of AIDS-related complex were explored based on a cross-section study that had been conducted to observe the personality and clinical features of the cases with AIDS-related complex. Results The qualitative systematic analysis suggested that the idiopathic CD4+ T lymphocytopenia (ICL) and infection of

  10. Caracterização imunofenotípica das subpopulações de linfócitos do lavado broncoalveolar de pacientes com silicose Phenotypic characterization of lymphocyte subsets in bronchoalveolar lavage of patients with silicosis

    Directory of Open Access Journals (Sweden)

    ÂNGELA FERREIRA

    2000-06-01

    dusts. The aim of this study was to characterize the lymphocyte subsets in bronchoalveolar lavage of patients with silicosis. Bronchoalveolar lavage was carried out in 26 workers with different forms of silicosis: simple form (n = 12, complicated (n = 13 and 1 patient with acute form of the disease. As a control group, 7 healthy individuals were included. Compared to the control group, silicotic patients showed intense pleocytosis constituted mainly by alveolar macrophages with slight lymphocytosis. Lymphocyte subsets present in the bronchoalveolar fluid (BAL of normal individuals were mature lymphocytes with phenotype CD2+TCRab (87.3% and only 2.9% were CD2+TCRgd. CD4/CD8 ratio was 1.8 with few (16% immature double negative T cells subsets (CD4-CD8-. In contrast, silicotic patients showed reduction of the more mature lymphocyte subset CD2+CD4+, CD2+CD8+ and a great increase (47% of immature (CD4-CD8- T cell subsets. No increase in the NK (CD56+ cell population was observed. Biochemical analysis of protein contents and determination of the Ig/albumin ratio characterized local immunoglobulin production within the pulmonary microenvironment. Furthermore, lack of increase of plasma cells, as well as the maintenance of the percentage of B lymphocyte population (CD19+ in the BAL of silicotic patients, favors the hypothesis that the cells responsible for Ig production are possibly located in the interstitial space. Altogether the results suggest development of lymphopoiesis and tertiary lymphoid tissue within the pulmonary microenvironment during the clinical course of silicosis.

  11. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

    Science.gov (United States)

    Kim, Sung-Bae; Dent, Rebecca; Im, Seock-Ah; Espié, Marc; Blau, Sibel; Tan, Antoinette R; Isakoff, Steven J; Oliveira, Mafalda; Saura, Cristina; Wongchenko, Matthew J; Kapp, Amy V; Chan, Wai Y; Singel, Stina M; Maslyar, Daniel J; Baselga, José

    2017-10-01

    The oral AKT inhibitor ipatasertib is being investigated in cancers with a high prevalence of PI3K/AKT pathway activation, including triple-negative breast cancer. The LOTUS trial investigated the addition of ipatasertib to paclitaxel as first-line therapy for triple-negative breast cancer. In this randomised, placebo-controlled, double-blind, phase 2 trial, women aged 18 years or older with measurable, inoperable, locally advanced or metastatic triple-negative breast cancer previously untreated with systemic therapy were recruited from 44 hospitals in South Korea, the USA, France, Spain, Taiwan, Singapore, Italy, and Belgium. Enrolled patients were randomly assigned (1:1) to receive intravenous paclitaxel 80 mg/m(2) (days 1, 8, 15) with either ipatasertib 400 mg or placebo once per day (days 1-21) every 28 days until disease progression or unacceptable toxicity. Randomisation was by stratified permuted blocks (block size of four) using an interactive web-response system with three stratification criteria: previous (neo)adjuvant therapy, chemotherapy-free interval, and tumour PTEN status. The co-primary endpoints were progression-free survival in the intention-to-treat population and progression-free survival in the PTEN-low (by immunohistochemistry) population. This ongoing trial is registered with ClinicalTrials.gov (NCT02162719). Between Sept 2, 2014, and Feb 4, 2016, 166 patients were assessed for eligibility and 124 patients were enrolled and randomly assigned to paclitaxel plus ipatasertib (n=62) or paclitaxel plus placebo (n=62). Median follow-up was 10·4 months (IQR 6·5-14·1) in the ipatasertib group and 10·2 months (6·0-13·6) in the placebo group. Median progression-free survival in the intention-to-treat population was 6·2 months (95% CI 3·8-9·0) with ipatasertib versus 4·9 months (3·6-5·4) with placebo (stratified hazard ratio [HR] 0·60, 95% CI 0·37-0·98; p=0·037) and in the 48 patients with PTEN-low tumours, median progression

  12. A novel double-negative feedback loop between miR-489 and the HER2-SHP2-MAPK signaling axis regulates breast cancer cell proliferation and tumor growth.

    Science.gov (United States)

    Patel, Yogin; Shah, Nirav; Lee, Ji Shin; Markoutsa, Eleni; Jie, Chunfa; Liu, Shou; Botbyl, Rachel; Reisman, David; Xu, Peisheng; Chen, Hexin

    2016-04-05

    Human epidermal growth factor receptor 2 (HER2 or ErBb2) is a receptor tyrosine kinase overexpressed in 20-30% of breast cancers and associated with poor prognosis and outcome. Dysregulation of several microRNAs (miRNAs) plays a key role in breast cancer progression and metastasis. In this study, we screened and identified miRNAs dysregualted in HER2-positive breast cancer cells. Our molecular study demonstrated that miR-489 was specifically downregulated by the HER2-downstream signaling, especially through the MAPK pathway. Restoration or overexpression of miR-489 in HER2-positive breast cancer cells significantly inhibited cell growth in vitro and decreased the tumorigenecity and tumor growth in xenograft mice. Mechanistically, we found that overexpression of miR-489 led to the decreased levels of HER2 and SHP2 and thus attenuated HER2-downstream signaling. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2-SHP2-MAPK and miR-489 signaling pathways form a mutually inhibitory loop. Using quantitative real-time PCR analysis and Fluorescent in situ hybridization technique (FISH), we found that miR-489 was expressed at significantly lower level in tumor tissues compared to the adjacent normal tissues. Downregulation of miR-489 in breast cancers was associated with aggressive tumor phenotypes. Overall, our results define a double-negative feedback loop involving miR-489 and the HER2-SHP2-MAPK signaling axis that can regulate breast cancer cell proliferation and tumor progression and might have therapeutic relevance for HER2-positive breast cancer.

  13. Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses

    Directory of Open Access Journals (Sweden)

    Barik Sailen

    2001-12-01

    Full Text Available Abstract Background Post-transcriptional gene silencing (PTGS by short interfering RNA has opened up new directions in the phenotypic mutation of cellular genes. However, its efficacy on non-nuclear genes and its effect on the interferon pathway remain unexplored. Since directed mutation of RNA genomes is not possible through conventional mutagenesis, we have tested sequence-specific 21-nucleotide long double-stranded RNAs (dsRNAs for their ability to silence cytoplasmic RNA genomes. Results Short dsRNAs were generated against specific mRNAs of respiratory syncytial virus, a nonsegmented negative-stranded RNA virus with a cytoplasmic life cycle. At nanomolar concentrations, the dsRNAs specifically abrogated expression of the corresponding viral proteins, and produced the expected mutant phenotype ex vivo. The dsRNAs did not induce an interferon response, and did not inhibit cellular gene expression. The ablation of the viral proteins correlated with the loss of the specific mRNAs. In contrast, viral genomic and antigenomic RNA, which are encapsidated, were not directly affected. Conclusions Synthetic inhibitory dsRNAs are effective in specific silencing of RNA genomes that are exclusively cytoplasmic and transcribed by RNA-dependent RNA polymerases. RNA-directed RNA gene silencing does not require cloning, expression, and mutagenesis of viral cDNA, and thus, will allow the generation of phenotypic null mutants of specific RNA viral genes under normal infection conditions and at any point in the infection cycle. This will, for the first time, permit functional genomic studies, attenuated infections, reverse genetic analysis, and studies of host-virus signaling pathways using a wild type RNA virus, unencumbered by any superinfecting virus.

  14. Novel INHAT repressor (NIR) is required for early lymphocyte development.

    Science.gov (United States)

    Ma, Chi A; Pusso, Antonia; Wu, Liming; Zhao, Yongge; Hoffmann, Victoria; Notarangelo, Luigi D; Fowlkes, B J; Jain, Ashish

    2014-09-23

    Novel inhibitor of histone acetyltransferase repressor (NIR) is a transcriptional corepressor with inhibitor of histone acetyltransferase activity and is a potent suppressor of p53. Although NIR deficiency in mice leads to early embryonic lethality, lymphoid-restricted deletion resulted in the absence of double-positive CD4(+)CD8(+) thymocytes, whereas bone-marrow-derived B cells were arrested at the B220(+)CD19(-) pro-B-cell stage. V(D)J recombination was preserved in NIR-deficient DN3 double-negative thymocytes, suggesting that NIR does not affect p53 function in response to physiologic DNA breaks. Nevertheless, the combined deficiency of NIR and p53 provided rescue of DN3L double-negative thymocytes and their further differentiation to double- and single-positive thymocytes, whereas B cells in the marrow further developed to the B220(+)CD19(+) pro-B-cell stage. Our results show that NIR cooperate with p53 to impose checkpoint for the generation of mature B and T lymphocytes.

  15. Isotropic Single Negative Metamaterials

    Directory of Open Access Journals (Sweden)

    P. Protiva

    2008-09-01

    Full Text Available This paper presents the application of simple, and therefore cheap, planar resonators for building 3D isotropic metamaterials. These resonators are: a broadside-coupled split ring resonator with a magnetic response providing negative permeability; an electric dipole terminated by a loop inductor together with a double H-shaped resonator with an electric response providing negative permittivity. Two kinds of 3D isotropic single negative metamaterials are reported. The first material consists of unit cells in the form of a cube bearing on its faces six equal planar resonators with tetrahedral symmetry. In the second material, the planar resonators boxed into spherical plastic shells and randomly distributed in a hosting material compose a real 3D volumetric metamaterial with an isotropic response. In both cases the metamaterial shows negative permittivity or permeability, according to the type of resonators that are used. The experiments prove the isotropic behavior of the cells and of the metamaterial specimens.

  16. IL-17-producing double-negative T cells are expanded in the peripheral blood, infiltrate the salivary gland and are partially resistant to corticosteroid therapy in patients with Sjögren’s syndrome

    Directory of Open Access Journals (Sweden)

    A. Alunno

    2013-10-01

    Full Text Available A small CD3+ T-cell population, that lacks both CD4 and CD8 molecules, defined as double negative (DN, is expanded in the peripheral blood of patients with systemic lupus erythematosus, produces IL-17 and accumulates in the kidney during lupus nephritis. Since IL-17 production is enhanced in salivary gland infiltrates of patients with primary Sjögren’s syndrome (pSS, we aimed to investigate whether DN T cells may be involved in the pathogenesis of salivary gland damage. Fifteen patients with SS and 15 normal controls (NC were enrolled. Peripheral blood mononuclear cells were stimulated with anti-CD3 antibody and cultured in presence or absence of dexamethasone (Dex. Phenotypic characterization was performed by flow cytometry in freshly isolated cells and after culture. Minor salivary glands (MSG from pSS were processed for immunofluorescence staining. Total circulating DN T cells were increased in pSS compared to NC (4.7±0.4% vs 2.6±0.4%. NC and pSS freshly isolated DN T cells produce consistent amounts of IL-17 (67.7±5.6 in NC vs 69.2±3.3 in pSS. Notably, DN T cells were found in the pSS-MSG infiltrate. Dex was able to down-regulate IL-17 in vitro production in NC (29±2.6% vs 15.2±1.9% vs 13±1.6% and pSS (49±4.8% vs 16±3.8% vs 10.2±0.8% conventional Th17 cells and in DN T cells of NC (80±2.8% vs 3.8±2.1% vs 4.2±1.8%, but not of pSS (81±1.5% vs 85.4±0.8% vs 86.2±1.7%. DN T cells are expanded in pSS PB, produce IL-17 and infiltrate pSS MSG. In pSS, conventional Th17 cells are inhibited by Dex, but DN T cells appear to be resistant to this effect. Taken together, these data suggest a key role of this T-cell subset in the perpetuation of chronic sialoadenitis and eventually in pSS prognosis.

  17. {sup 18}F-FDG PET patterns and BAL cell profiles in pulmonary sarcoidosis

    Energy Technology Data Exchange (ETDEWEB)

    Keijsers, Ruth G.; Verzijlbergen, Fred J. [St Antonius Hospital, Department of Nuclear Medicine, Postbox 2500, Nieuwegein (Netherlands); Grutters, Jan C.; Bosch, Jules M. van den [St Antonius Hospital, Department of Pulmonology, Nieuwegein (Netherlands); Velzen-Blad, Heleen van [St Antonius Hospital, Medical Microbiology and Immunology, Nieuwegein (Netherlands); Oyen, Wim J. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)

    2010-06-15

    Bronchoalveolar lavage (BAL) and {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) PET can both demonstrate sarcoid activity. To assess whether metabolic activity imaged by {sup 18}F-FDG PET represents signs of disease activity as reflected by BAL, {sup 18}F-FDG PET patterns were compared with BAL cell profiles. In this retrospective analysis, 77 newly diagnosed pulmonary sarcoidosis patients underwent BAL and {sup 18}F-FDG PET. Based on {sup 18}F-FDG PET, patients were diagnosed with exclusively mediastinal/hilar activity (group A) and activity in the lung parenchyma (group B). Per group, BAL lymphocytes (%), CD4/CD8 ratio, CD103{sup +}CD4{sup +}/CD4{sup +} ratio and neutrophils (%) were compared with the extent of metabolic activity expressed as the maximum standardized uptake value (SUV{sub max}). Additionally, SUV{sub max} and BAL parameters per radiographic stage were analysed. Overall, the SUV{sub max} in the lung parenchyma correlated with neutrophils and SUV{sub max} of the mediastinum/hila correlated with the CD4/CD8 ratio. In both groups, a significant, negative correlation between the SUV{sub max} of the mediastinum/hila and the CD103{sup +}CD4{sup +}/CD4{sup +} ratio was found. In group B, the SUV{sub max} of the mediastinum/hila correlated with the CD4/CD8 ratio, while the SUV{sub max} in the lung parenchyma correlated with the CD103{sup +}CD4{sup +}/CD4{sup +} ratio and neutrophils. Significant differences were found in the SUV{sub max}, CD4/CD8 ratio, CD103{sup +}CD4{sup +}/CD4{sup +} ratio and neutrophils between the radiographic stages. The SUV{sub max} of the lung parenchyma was positively related to the radiographic stage, while the SUV{sub max} of the mediastinum/hila and CD4/CD8 ratio were inversely related. {sup 18}F-FDG PET correlates with the CD4/CD8 ratio and neutrophils, suggesting that {sup 18}F-FDG PET represents this specific cell profile in BAL. High SUV{sub max} values of the lung parenchyma may therefore correlate with more severe

  18. Surface molecules that drive T cell development in vitro in the absence of thymic epithelium and in the absence of lineage-specific signals.

    Science.gov (United States)

    Cibotti, R; Punt, J A; Dash, K S; Sharrow, S O; Singer, A

    1997-03-01

    Differentiation of immature double positive (DP) CD4+ CD8+ thymocytes into single positive (SP) CD4+ and CD8+ T cells is referred to as positive selection and requires physical contact with thymic cortical epithelium. We now have identified "coinducer" molecules on DP thymocytes that, together with TCR, signal DP thymocytes to differentiate into SP T cells in vitro in the absence of thymic epithelium. A remarkable number of different molecules on DP thymocytes possessed "coinducing" activity, including CD2, CD5, CD24, CD28, CD49d, CD81, and TSA-1. Interestingly, in vitro differentiation occurred in the absence of lineage-specific signals, yet resulted in the selective generation of CD4+CD8- T cells. Thus, the present study has identified surface molecules that can signal DP thymocytes to differentiate into SP T cells in the absence of thymic epithelium and has characterized a default pathway for CD4+ T cell differentiation.

  19. Double Trouble

    NARCIS (Netherlands)

    Elsaesser, Thomas; Kievit, Robert; Simons, Jan

    1994-01-01

    Double Trouble highlights the career of Dutch scriptwriter and television producer Chiem van Houweninge, well-known for his long-running TV comedy series and as author of episodes for TV detective series. Double Trouble gives Van Houweninge's own views on writing and filming in television prime impo

  20. Double Trouble

    NARCIS (Netherlands)

    Elsaesser, Thomas; Kievit, Robert; Simons, Jan

    1994-01-01

    Double Trouble highlights the career of Dutch scriptwriter and television producer Chiem van Houweninge, well-known for his long-running TV comedy series and as author of episodes for TV detective series. Double Trouble gives Van Houweninge's own views on writing and filming in television prime

  1. Detailing profiles of Lawsonia intracellularis specific lymphocytes in the immune response to a challenge inoculation after oral vaccination or primary inoculation with virulent bacteria

    DEFF Research Database (Denmark)

    Riber, Ulla; Hvass, Henriette Cordes; Heegaard, Peter M. H.;

    2012-01-01

    , the vaccinated pigs did not show any immediate evidence of primed (faster or stronger) IgG or CMI response compared to naïve pigs. L. intracellularis-specific CMI responses 18-33 dpi were further characterized by flow cytometry for intracellular IFN-γ and cell proliferation (CFSE). Phenotypes of IFN-γ producing...... cells in the vaccinated pigs showed profiles primarily of CD8+(CD4neg) and CD4+CD8+ double positive lymphocytes. Similar profiles of IFN-γ producing cells were found in re-inoculated immune pigs, which experienced a boost in CMI responses. Cellular proliferation was identified in nearly all vaccinated...... pigs with mainly CD4+(CD8neg) and CD4+CD8+ double positive cells, whereas the immune re-inoculated pigs also included response in CD8high(CD4neg) cells. These different profiles of responsive cellular phenotypes may influence the observed differences in protection between vaccinated and re...

  2. Somatic mosaicism for a NRAS mutation associates with disparate clinical features in RAS-associated leukoproliferative disease: a report of two cases.

    Science.gov (United States)

    Shiota, Mitsutaka; Yang, Xi; Kubokawa, Mei; Morishima, Tatsuya; Tanaka, Kuniaki; Mikami, Masamitsu; Yoshida, Kenichi; Kikuchi, Masako; Izawa, Kazushi; Nishikomori, Ryuta; Okuno, Yusuke; Wang, Xian; Sakaguchi, Hirotoshi; Muramatsu, Hideki; Kojima, Seiji; Miyano, Satoru; Ogawa, Seishi; Takagi, Masatoshi; Hata, Daisuke; Kanegane, Hirokazu

    2015-07-01

    RAS-associated leukoproliferative disease (RALD) is a newly classified disease; thus its clinical features and management are not fully understood. The cases of two patients with characteristic features of RALD are described herein. Patient 1 was a 5-month-old female with clinical features typical of autoimmune lymphoproliferative syndrome (ALPS) and markedly elevated TCRαβ(+)CD4(-)CD8(-) T cell numbers. Genetic analyses failed to detect an ALPS-related gene mutation; however, whole exome sequencing and other genetic analyses revealed somatic mosaicism for the G13D NRAS mutation. These data were indivative of NRAS-associated RALD with highly elevated αβ-double-negative T cells. Patient 2 was a 12-month-old girl with recurrent fever who clearly met the diagnostic criteria for juvenile myelomonocytic leukemia (JMML). Genetic analyses revealed somatic mosaicism, again for the G13D NRAS mutation, suggesting RALD associated with somatic NRAS mosaicism. Notably, unlike most JMML cases, Patient 2 did not require steroids or hematopoietic stem cell transplantation. Genetic analysis of RAS should be performed in patients fulfilling the diagnostic criteria for ALPS in the absence of ALPS-related gene mutations if the patients have elevated αβ-double-negative-T cells and in JMML patients if autoimmunity is detected. These clinical and experimental data increase our understanding of RALD, ALPS, and JMML.

  3. IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes.

    Science.gov (United States)

    Boggio, Elena; Clemente, Nausicaa; Mondino, Anna; Cappellano, Giuseppe; Orilieri, Elisabetta; Gigliotti, Casimiro L; Toth, Erika; Ramenghi, Ugo; Dianzani, Umberto; Chiocchetti, Annalisa

    2014-02-20

    In autoimmune/lymphoproliferative syndrome (ALPS), defective Fas death receptor function causes lymphadenomegaly/splenomegaly, the expansion of T-cell receptor αβ(+) CD4/CD8 double-negative T cells, and frequent development of hematologic autoimmunity. Dianzani autoimmune lymphoproliferative disease (DALD) has a similar phenotype but lacks the expansion of double-negative T cells. This work shows that patients with ALPS and DALD have high serum levels of interleukin 17A (IL-17A), IL-17F, and IL-17AF, which are involved in several autoimmune diseases, and that their T cells show increased secretion of these cytokines upon activation in vitro. The following data indicate that these cytokines may contribute to ALPS and DALD: (1) recombinant IL-17A and IL-17F significantly inhibit Fas-induced cell death in Fas-sensitive T cells from healthy donors; (2) this inhibitory effect is also induced by the patients' serum and is reversed by anti-IL-17A antibodies; (3) IL-17A neutralization substantially increases Fas-induced cell death in T cells from ALPS and DALD patients in vitro; and (4) treatment with anti-IL-17A antibodies ameliorates the autoimmune manifestations and, at a lesser extent, the lymphoproliferative phenotype and prolongs survival in MRLlpr/lpr mice, which are an animal model of ALPS. These data suggest that IL-17A and IL-17F could be targeted therapeutically to improve Fas function in ALPS and DALD.

  4. Negative learning

    Energy Technology Data Exchange (ETDEWEB)

    Oppenheimer, M. [Woodrow Wilson School of Public and International Affairs, Department of Geosciences, Princeton University, Princeton, NJ (United States); O' Neill, B.C. [International Institute for Applied Systems Analysis, Laxenburg (Austria)]|[Institute for the Study of Society and Environment, National Center for Atmospheric Research, Boulder, CO (United States); Webster M. [MIT Joint Program on the Science and Policy of Global Change, Massachusetts Institute of Technology, Cambridge, MA (United States)

    2008-07-15

    New technical information may lead to scientific beliefs that diverge over time from the a posteriori right answer. We call this phenomenon, which is particularly problematic in the global change arena, negative learning. Negative learning may have affected policy in important cases, including stratospheric ozone depletion, dynamics of the West Antarctic ice sheet, and population and energy projections. We simulate negative learning in the context of climate change with a formal model that embeds the concept within the Bayesian framework, illustrating that it may lead to errant decisions and large welfare losses to society. Based on these cases, we suggest approaches to scientific assessment and decision making that could mitigate the problem. Application of the tools of science history to the study of learning in global change, including critical examination of the assessment process to understand how judgments are made, could provide important insights on how to improve the flow of information to policy makers.

  5. Study on T lymphocyte subsets and NK cells in patients with Graves' disease combined with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Wei Feng; Du Jing; Su Xiulan; Wu Lan; Wang Jinjing; Huo Xiaojing

    2008-01-01

    Objective To investigate changes in T lymphocyte subsets and NK cells in patients with simple Graves' disease (GD)and Graves' disease combined with type 2 diabetes mellitus (GD/T2DM). Methods Fifteen cases of GD/ T2DM were selected from our hospital from November 2001 to November 2004. Before and after therapy thyroid function, thyroglobulin antibody (TGA), thyroid microsomal antibody (TMA) and blood glucose level were measured, and T lymphocyte subsets (CD3, CD4, CD8, CD4/CD8) and NK cells (CD56) were measured by immunofluorescence double labeling monoclonal antibody and flow cytometry, respectively. At the same time, comparison was made with simple GD (15 cases), T2DM (15 cases) and healthy control (20 cases). Results Before therapy, CD4/CD8, CD4 and NK cells in GD/T2DM were less than normal, and there was no significant difference in comparison with simple GD (P<0.05). In T2DM group, only CD4/CD8 and CD4 were less than those of healthy controls (P<0.05). When thyroid function recovered after 1 to 3 months of methimazole treatment in both GD/T2DM and simple GD groups, various indexes recovered, which were more obvious in simple GD. Conclusion Immune hypofunction of GD may be the key to the immune abnormality of GD/T2DM, which is more significant than that of simple GD or T2DM. The recovery of thyroid function and immune abnormality is not consistent, and the recovery of GD is more significant than that of GD/T2DM.

  6. Role of SLAM in NKT cell development revealed by transgenic complementation in NOD mice.

    Science.gov (United States)

    Jordan, Margaret A; Fletcher, Julie M; Jose, Roby; Chowdhury, Shahead; Gerlach, Nicole; Allison, Janette; Baxter, Alan G

    2011-04-01

    Allelic variation of SLAM expression on CD4(+)CD8(+) thymocytes has been proposed to play a major role in NKT cell development. In this article, this hypothesis is tested by the production of subcongenic mouse strains and Slamf1 transgenic lines. The long isoform of the C57BL/6 allele of Slamf1 was transgenically expressed on CD4(+)CD8(+) thymocytes under control of an hCD2 minigene. NOD.Nkrp1b.Tg(Slamf1)1 mice, which had a 2-fold increase in SLAM protein expression on CD4(+)CD8(+) thymocytes, had a 2-fold increase in numbers of thymic NKT cells. The additional thymic NKT cells in NOD.Nkrp1b.Tg(Slamf1)1 mice were relatively immature, with a similar subset distribution to those of congenic NOD.Nkrp1b.Nkt1 and NOD.Nkrp1b.Slamf1 mice, which also express increased levels of SLAM on CD4(+)CD8(+) thymocytes and produce larger numbers of NKT cells. Transgenic enhancement of SLAM expression also increased IL-4 and IL-17 production in response to TCR-mediated stimulation. Paradoxically, NOD.Nkrp1b.Tg(Slamf1)2 mice, which had a 7-fold increase in SLAM expression, showed no significant increase in NKT cells numbers; on the contrary, at high transgene copy number, SLAM expression levels correlated inversely with NKT cell numbers, consistent with a contribution to negative selection. These data confirm a role for SLAM in controlling NKT cell development and are consistent with a role in both positive and negative thymic selection of NKT cells.

  7. Changes in circulating lymphocyte subpopulations in pigs receiving therapeutic doses of ceftiofur and tulathromycin

    Directory of Open Access Journals (Sweden)

    Czyżewska-Dors Ewelina

    2016-12-01

    Full Text Available Introduction: The aim of the study was to evaluate the effect of administration of therapeutic doses of ceftiofur and tulathromycin on the circulating lymphocyte subpopulations in healthy pigs. Material and Methods: The study was conducted on thirty healthy 7- to 10-week-old pigs, assigned to three groups: the TUL group, injected with tulathromycin (n = 10; the CEF group, injected with ceftiofur (n = 10; and the C group, the control with no antibiotic administration (n = 10. Blood samples were collected before, during, and after treatment with antimicrobials. Lymphocyte subpopulations circulating in the blood were determined by immunostaining and flow cytometry analyses. Results: Following administration of a therapeutic dose of tulathromycin, there were no changes in the lymphocyte subpopulations circulating in blood. In contrast, administration of ceftiofur at the recommended dose decreased the absolute number of CD3+, CD21+, CD4+CD8-, CD4-CD8+, and double positive CD4CD8 cells. Conclusion: Results from the study indicate that ceftiofur possesses the ability to modulate the immune system in healthy pigs by decreasing lymphocyte subpopulations circulating in blood.

  8. Effect of transoral endoscopic adenoidectomy on peripheral blood T-lymphocyte subsets in children with obstructive sleep apnea-hypopnea syndrome and its treatment strategy.

    Science.gov (United States)

    Yang, Na; Ji, Yaofeng; Liu, Yin

    2017-10-01

    The objective of the present study was to investigate the effect of transoral endoscopic adenoidectomy on peripheral blood T lymphocyte subsets in pediatric patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and its treatment strategy. Ninety-eight pediatric patients with adenoidal hypertrophy associated with OSAHS admitted to the Department of Otolaryngology, Xuzhou Children's Hospital were selected. After admission, patients received perfected 24 h polysomnogram monitoring, routine blood examination, fasting blood biochemistry examination, T-lymphocyte subset count, 24 h ambulatory blood pressure monitoring, and nasopharyngeal computed tomography. After patients were diagnosed with adenoidal hypertrophy associated with OSAHS, they underwent transoral endoscopic adenoidectomy with a power microdebrider. Patients were evaluated at 3-, 6- and 12-week follow-up visits. The CD3(+), CD4(+), and CD8(+) T-cell counts, CD4(+)/CD8(+) T lymphocyte ratio, and changes of 24 h ambulatory blood pressure before and after surgery were recorded. After the 6-week follow-up visit, the mean CD4(+) T lymphocyte count in patients was increased significantly compared with that before surgery, the CD4(+)/CD8(+) T lymphocyte ratio increased gradually, and the differences were statistically significant (PT lymphocyte ratio was negatively correlated with mean arterial pressure (MAP) (r=-1.06, P=0.003). In conclusion, adenoidectomy can significantly decrease the MAP in pediatric patients with OSAHS and increase the duration of nocturnal sleep. The peripheral blood CD4(+)/CD8(+) T lymphocyte ratio in pediatric patients was significantly negatively correlated with MAP.

  9. Negative Certainty

    Science.gov (United States)

    Ariso, José María

    2017-01-01

    The definitions of "negative knowledge" and the studies in this regard published to date have not considered the categorial distinction Wittgenstein established between knowledge and certainty. Hence, the important role that certainty, despite its omission, should have in these definitions and studies has not yet been shown. In this…

  10. Negative Numbers

    Science.gov (United States)

    Galbraith, Mary J.

    1974-01-01

    Examination of models for representing integers demonstrates that formal operational thought is required for establishing the operations on integers. Advocated is the use of many models for introducing negative numbers but, apart from addition, it is recommended that operations on integers be delayed until the formal operations stage. (JP)

  11. Negative Certainty

    Science.gov (United States)

    Ariso, José María

    2017-01-01

    The definitions of "negative knowledge" and the studies in this regard published to date have not considered the categorial distinction Wittgenstein established between knowledge and certainty. Hence, the important role that certainty, despite its omission, should have in these definitions and studies has not yet been shown. In this…

  12. T-cell-specific deletion of Mof blocks their differentiation and results in genomic instability in mice.

    Science.gov (United States)

    Gupta, Arun; Hunt, Clayton R; Pandita, Raj K; Pae, Juhee; Komal, K; Singh, Mayank; Shay, Jerry W; Kumar, Rakesh; Ariizumi, Kiyoshi; Horikoshi, Nobuo; Hittelman, Walter N; Guha, Chandan; Ludwig, Thomas; Pandita, Tej K

    2013-05-01

    Ataxia telangiectasia patients develop lymphoid malignancies of both B- and T-cell origin. Similarly, ataxia telangiectasia mutated (Atm)-deficient mice exhibit severe defects in T-cell maturation and eventually develop thymomas. The function of ATM is known to be influenced by the mammalian orthologue of the Drosophila MOF (males absent on the first) gene. Here, we report the effect of T-cell-specific ablation of the mouse Mof (Mof) gene on leucocyte trafficking and survival. Conditional Mof(Flox/Flox) (Mof (F/F)) mice expressing Cre recombinase under control of the T-cell-specific Lck proximal promoter (Mof(F/F)/Lck-Cre(+)) display a marked reduction in thymus size compared with Mof(F/F)/Lck-Cre(-) mice. In contrast, the spleen size of Mof(F/F)/Lck-Cre(+) mice was increased compared with control Mof(F/F)/Lck-Cre(-) mice. The thymus of Mof(F/F)/Lck-Cre(+) mice contained significantly reduced T cells, whereas thymic B cells were elevated. Within the T-cell population, CD4(+)CD8(+) double-positive T-cell levels were reduced, whereas the immature CD4(-)CD8(-) double-negative (DN) population was elevated. Defective T-cell differentiation is also evident as an increased DN3 (CD44(-)CD25(+)) population, the cell stage during which T-cell receptor rearrangement takes place. The differentiation defect in T cells and reduced thymus size were not rescued in a p53-deficient background. Splenic B-cell distributions were similar between Mof(F/F)/Lck-Cre(+) and Mof(F/F)/Lck-Cre(-) mice except for an elevation of the κ light-chain population, suggestive of an abnormal clonal expansion. T cells from Mof(F/F)/Lck-Cre(+) mice did not respond to phytohaemagglutinin (PHA) stimulation, whereas LPS-stimulated B cells from Mof(F/F)/Lck-Cre(+) mice demonstrated spontaneous genomic instability. Mice with T-cell-specific loss of MOF had shorter lifespans and decreased survival following irradiation than did Mof(F/F)/Lck-Cre(-) mice. These observations suggest that Mof plays a critical

  13. Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes.

    Science.gov (United States)

    Patrick, Michael S; Oda, Hiroyo; Hayakawa, Kunihiro; Sato, Yoshinori; Eshima, Koji; Kirikae, Teruo; Iemura, Shun-Ichiro; Shirai, Mutsunori; Abe, Takaya; Natsume, Tohru; Sasazuki, Takehiko; Suzuki, Harumi

    2009-09-22

    T cells develop in the thymus through positive and negative selection, which are responsible for shaping the T cell receptor (TCR) repertoire. To elucidate the molecular mechanisms involved in selection remains an area of intense interest. Here, we identified and characterized a gene product Gasp (Grb2-associating protein, also called Themis) that is critically required for positive selection. Gasp is a cytosolic protein with no known functional motifs that is expressed only in T cells, especially immature CD4/CD8 double positive (DP) thymocytes. In the absence of Gasp, differentiation of both CD4 and CD8 single positive cells in the thymus was severely inhibited, whereas all other TCR-induced events such as beta-selection, negative selection, peripheral activation, and homeostatic proliferation were unaffected. We found that Gasp constitutively associates with Grb2 via its N-terminal Src homology 3 domain, suggesting that Gasp acts as a thymocyte-specific adaptor for Grb2 or regulates Ras signaling in DP thymocytes. Collectively, we have described a gene called Gasp that is critical for positive selection.

  14. Double supergeometry

    CERN Document Server

    Cederwall, Martin

    2016-01-01

    A geometry of superspace corresponding to double field theory is developed, with type II supergravity in D=10 as the main example. The formalism is based on an orthosymplectic extension OSp(d,d|2s) of the continuous T-duality group. Covariance under generalised super-diffeomorphisms is manifest. Ordinary superspace is obtained as a solution of the orthosymplectic section condition. A systematic study of curved superspace Bianchi identities is performed, and a relation to a double pure spinor superfield cohomology is established. A Ramond-Ramond superfield is constructed as an infinite-dimensional orthosymplectic spinor. Such objects in minimal orbits under the OSp supergroup ("pure spinors") define super-sections.

  15. Double screening

    Energy Technology Data Exchange (ETDEWEB)

    Gratia, Pierre [Department of Physics, University of Chicago,South Ellis Avenue, Chicago, IL 60637 (United States); Hu, Wayne [Department of Astronomy and Astrophysics, University of Chicago,South Ellis Avenue, Chicago, IL 60637 (United States); Enrico Fermi Institute and Kavli Institute for Cosmological Physics, University of Chicago,South Ellis Avenue, Chicago, IL 60637 (United States); Joyce, Austin [Enrico Fermi Institute and Kavli Institute for Cosmological Physics, University of Chicago,South Ellis Avenue, Chicago, IL 60637 (United States); Ribeiro, Raquel H. [School of Physics and Astronomy, Queen Mary University of London,Mile End Road, London, E1 4NS (United Kingdom)

    2016-06-15

    Attempts to modify gravity in the infrared typically require a screening mechanism to ensure consistency with local tests of gravity. These screening mechanisms fit into three broad classes; we investigate theories which are capable of exhibiting more than one type of screening. Specifically, we focus on a simple model which exhibits both Vainshtein and kinetic screening. We point out that due to the two characteristic length scales in the problem, the type of screening that dominates depends on the mass of the sourcing object, allowing for different phenomenology at different scales. We consider embedding this double screening phenomenology in a broader cosmological scenario and show that the simplest examples that exhibit double screening are radiatively stable.

  16. TRIO-012: a multicenter, multinational, randomized, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer.

    Science.gov (United States)

    Mackey, John; Gelmon, Karen; Martin, Miguel; McCarthy, Nicole; Pinter, Tamas; Rupin, Mathieu; Youssoufian, Hagop

    2009-11-01

    In this multinational, placebo-controlled, randomized phase III trial, Translational Research In Oncology (TRIO) will define the efficacy and safety of adding a novel antiangiogenic agent, IMC-1121B (ramucirumab), to standard first-line docetaxel chemotherapy for women with HER2-negative metastatic breast cancer. We will evaluate whether the addition of IMC-1121B prolongs progression-free survival and whether its use improves overall survival. Accrual is under way.

  17. γ-干扰素释放试验对HIV感染者合并菌阴肺结核辅助诊断价值的探讨%Auxiliary diagnostic value of interferon-γrelease assay in HIV and pulmonary tuberculosis with negative cul-ture

    Institute of Scientific and Technical Information of China (English)

    张林; 李琦

    2016-01-01

    value of interferon-γ release assays ( IGRAs) for human immunodeficiency virus infection and pulmonary tuberculosis with negative culture. Methods The clinical data of 128 cases of negative HIV pulmonary tuberculosis, HIV/AIDS and pulmonary tuberculosis by IGRAs were ret-rospectively analyzed. Rate within the group and between groups were compared by chi-square test. T test was used for measurement data. Taking positive or negative results of IGRAs as the dependent variable factor, it used logistic regression (parameter estimation based on the condition of backward method) to analyze the results. Results (1) The level of blood interferon-γ and the positive detection rate were higher in HIV and pulmonary tuberculosis with negative culture patients than in patients with HIV/AIDS (U=7. 813, P=0. 005;chi-square=8. 486, P=0. 004), but it was close to pulmonary tuberculosis with negative culture patients ( U =1. 109, P =0. 292; chi-square =2. 459, P=0. 117). (2) Compared with negative HIV/ pulmonary tuberculosis patients, the level of of CD4+, lymphocyte count and CD4+ /CD8+ increased obviously in IGRAs positive HIV/ pulmonary tuberculosis patients ( t=5. 349, P=0. 002;t=2. 834, P =0. 009; t =5. 576, P <0. 001), and blood sedimentation decreased (t = -2. 317, P=0. 029). (3) Logistic regression analysis showed that CD4+ was independent factor for HIV/ pulmonary tuberculosis with negative culture (Waldχ2 =4. 434, P=0. 035, OR=13. 5, 95% CI=1. 197 -152. 211). (4) The sensitivity of IGRAs detection was 35. 7%, and the diagnosis accuracy was 72. 7%, which were higher than tu-berculosis antibody (21. 4%, 63. 6%) and PPD (14. 2%, 67. 0%) in HIV/ pulmonary tuberculosis with negative culture. Its specific degree was 90. 0%, which was similar with PPD (91. 7%) and slightly higher than tuberculosis antibody (83. 3%). The detection sensitivity of IGRAs joint PPD and tuberculosis antibody was up to 60. 7%. Con-clusion IGRAS can help to sieve out early from HIV patients or find HIV

  18. Double Imbalance

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The government has been introducing a string of policies to stabilize the economy and cushion the impact of the global eco-nomic slowdown since October.These policies are generally deemed"timely"and"necessary,"but not a long-term cure for problems in China’s economy.Renowned economist Wu Jinglian says the country must address its"double imbalance"and further reform its economic growth mode.He made his comments at the First Annual Global Management Forum on December 6 in Shanghai.Excerptsf ollow:

  19. Variation of T cell subset during acute rejection after liver transplantation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Ran Jiang-hua; Liu Jing; Zhang Xi-bing; Zhang Sheng-ning; Wu Shu-yuan; Li Lai-bang; Li Wang; Li Li

    2014-01-01

    Abstract BACKGROUND: Looking for the early diagnosis of acute rejection indicators after liver transplantation can assess the risk after liver transplantation quickly and effectively, and T lymphocytes play the significant role in acute rejection. OBJECTIVE:To observe the relationship between acute rejection and variation of expression of T cel subset in blood after liver transplantation in rhesus monkey. METHODS: The sixteen liver transplant models in rhesus monkey which were constructed successfuly by the method of “double-cuff and one support tube” were divided into two groups randomly: experiment group (no treated by immunosuppressant in perioperative period) and control group (treated by immunosuppressant in perioperative period). Then the blood specimen and liver tissue respectively were colected at 6, 12, 24 and 72 hours after operation. The levels of alanine transferase, aspartate aminotransferase, and total bilirubin were detected with the fuly automatic biochemical analyser. The levels of CD4+/CD8+were tested by flow cytometry. The liver tissue in rhesus monkey after liver transplantation was detected by hematoxylin-eosin staining. The degree of acute rejection was evaluated by Banff Score System. RESULTS AND CONCLUSION: Acute rejection appeared in the experiment group at 12, 24, and 72 hours after liver transplantation. Levels of alanine transferase, aspartate aminotransferase, and total bilirubin were significantly higher in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). The expression of CD4+/CD8+of the experiment group and control group began to rise at 6 hours after surgery, but the experiment group increased the most obvious. CD4+/CD8+ expression was significantly greater in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). Morphological pathology was severer, and Banff score was higher in the experiment group than in the control group at

  20. Lymphocyte differentiation in sea bass thymus: CD4 and CD8-alpha gene expression studies.

    Science.gov (United States)

    Picchietti, Simona; Guerra, Laura; Buonocore, Francesco; Randelli, Elisa; Fausto, Anna Maria; Abelli, Luigi

    2009-07-01

    Different developmental stages (from eggs to 1-year-old juveniles) of the teleost fish Dicentrarchus labrax (L.) were assayed for CD4 gene expression. RT-PCR revealed the appearance of CD4 transcripts in post-larvae from 51 days post-hatching (dph). This finding overlaps the first detection of CD8-alpha mRNA. Real-time PCR with specific primers quantified CD4, CD8-alpha and TCR-beta transcripts in larvae and post-larvae (25, 51, 75 and 92 dph) and 1-year-old thymus. At 92 dph, TcR-beta and CD8-alpha transcripts were significantly higher (P overlap, except in the medulla, where CD4(+) thymocytes were isolated, while CD8-alpha(+) ones mainly arranged in cords. These results provide new information about the thymic compartmentalization and lymphocyte differentiation pathways in a teleost, almost demonstrating that double negative thymocytes fill the cortex giving rise to further selection in the medulla.

  1. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome.

    Science.gov (United States)

    Völkl, Simon; Rensing-Ehl, Anne; Allgäuer, Andrea; Schreiner, Elisabeth; Lorenz, Myriam Ricarda; Rohr, Jan; Klemann, Christian; Fuchs, Ilka; Schuster, Volker; von Bueren, André O; Naumann-Bartsch, Nora; Gambineri, Eleonora; Siepermann, Kathrin; Kobbe, Robin; Nathrath, Michaela; Arkwright, Peter D; Miano, Maurizio; Stachel, Klaus-Daniel; Metzler, Markus; Schwarz, Klaus; Kremer, Anita N; Speckmann, Carsten; Ehl, Stephan; Mackensen, Andreas

    2016-07-14

    Autoimmune lymphoproliferative syndrome (ALPS) is a human disorder characterized by defective Fas signaling, resulting in chronic benign lymphoproliferation and accumulation of TCRαβ(+) CD4(-) CD8(-) double-negative T (DNT) cells. Although their phenotype resembles that of terminally differentiated or exhausted T cells, lack of KLRG1, high eomesodermin, and marginal T-bet expression point instead to a long-lived memory state with potent proliferative capacity. Here we show that despite their terminally differentiated phenotype, human ALPS DNT cells exhibit substantial mitotic activity in vivo. Notably, hyperproliferation of ALPS DNT cells is associated with increased basal and activation-induced phosphorylation of serine-threonine kinases Akt and mechanistic target of rapamycin (mTOR). The mTOR inhibitor rapamycin abrogated survival and proliferation of ALPS DNT cells, but not of CD4(+) or CD8(+) T cells in vitro. In vivo, mTOR inhibition reduced proliferation and abnormal differentiation by DNT cells. Importantly, increased mitotic activity and hyperactive mTOR signaling was also observed in recently defined CD4(+) or CD8(+) precursor DNT cells, and mTOR inhibition specifically reduced these cells in vivo, indicating abnormal programming of Fas-deficient T cells before the DNT stage. Thus, our results identify the mTOR pathway as a major regulator of lymphoproliferation and aberrant differentiation in ALPS.

  2. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation.

    Science.gov (United States)

    Magerus-Chatinet, Aude; Neven, Bénédicte; Stolzenberg, Marie-Claude; Daussy, Cécile; Arkwright, Peter D; Lanzarotti, Nina; Schaffner, Catherine; Cluet-Dennetiere, Sophie; Haerynck, Filomeen; Michel, Gérard; Bole-Feysot, Christine; Zarhrate, Mohammed; Radford-Weiss, Isabelle; Romana, Serge P; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2011-01-01

    Autoimmune diseases develop in approximately 5% of humans. They can arise when self-tolerance checkpoints of the immune system are bypassed as a consequence of inherited mutations of key genes involved in lymphocyte activation, survival, or death. For example, autoimmune lymphoproliferative syndrome (ALPS) results from defects in self-tolerance checkpoints as a consequence of mutations in the death receptor-encoding gene TNF receptor superfamily, member 6 (TNFRSF6; also known as FAS). However, some mutation carriers remain asymptomatic throughout life. We have now demonstrated in 7 ALPS patients that the disease develops as a consequence of an inherited TNFRSF6 heterozygous mutation combined with a somatic genetic event in the second TNFRSF6 allele. Analysis of the patients' CD4(-)CD8(-) (double negative) T cells--accumulation of which is a hallmark of ALPS--revealed that in these cells, 3 patients had somatic mutations in their second TNFRSF6 allele, while 4 patients had loss of heterozygosity by telomeric uniparental disomy of chromosome 10. This observation provides the molecular bases of a nonmalignant autoimmune disease development in humans and may shed light on the mechanism underlying the occurrence of other autoimmune diseases.

  3. Autoimmune lymphoproliferative syndrome due to somatic FAS mutation (ALPS-sFAS) combined with a germline caspase-10 (CASP10) variation.

    Science.gov (United States)

    Martínez-Feito, Ana; Melero, Josefa; Mora-Díaz, Sergio; Rodríguez-Vigil, Carmen; Elduayen, Ramón; González-Granado, Luis I; Pérez-Méndez, Dolores; Sánchez-Zapardiel, Elena; Ruiz-García, Raquel; Menchén, Miguela; Díaz-Madroñero, Josefa; Paz-Artal, Estela; Del Orbe-Barreto, Rafael; Riñón, Marta; Allende, Luis M

    2016-01-01

    Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency caused by impaired Fas/FasL-mediated apoptosis of lymphocytes and is characterized by chronic nonmalignant or benign lymphoproliferation, autoimmune manifestations and expansion of double negative (DN) T-cells (TCRαβ+CD4-CD8-). Most cases of ALPS are associated with germline (ALPS-FAS) or somatic (ALPS-sFAS) heterozygous FAS mutations or a combination of both. Here we report three unrelated patients with ALPS-sFAS. Only one of them showed impaired Fas function in PHA-activated T-cells. In this patient, the genetic analysis of the caspase-10 gene (CASP10) identified a heterozygous germline change in exon 9 (c.1337A>G) causing Y446C substitution in the caspase-10 protein. In addition, this patient had a dysregulated T- and B-cell phenotype; circulating lymphocytes showed expansion of T effector memory CD45RA+ (TEMRA) CD4 T-cells, effector memory CD8 T-cells, CD21(low) B-cells and reduced memory switched B-cells. Additionally, this patient showed altered expression in T-cells of several molecules that change during differentiation from naïve to effector cells (CD27, CD95, CD57 and perforin). Molecular alterations in genes of the Fas pathway are necessary for the development of ALPS and this syndrome could be influenced by the concurrent effect of other mutations hitting different genes involved in Fas or related pathways.

  4. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS).

    Science.gov (United States)

    Teachey, David T; Manno, Catherine S; Axsom, Kelly M; Andrews, Timothy; Choi, John K; Greenbaum, Barbara H; McMann, Joseph M; Sullivan, Kathleen E; Travis, Susan F; Grupp, Stephan A

    2005-03-15

    Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of disrupted lymphocyte homeostasis. Clinical manifestations of ALPS vary but typically include autoimmune cytopenias, organomegaly, lymphadenopathy, and increased risk of malignancies. A similar spectrum of symptoms may be seen in some patients with Evans syndrome (ES), a hematologic disorder defined by autoimmune destruction of at least 2 hematologic cell types. We hypothesized that a subset of patients diagnosed with ES may have ALPS. We screened 12 children with ES by flow cytometric analysis for CD4-/CD8- (double negative) T cells (DNTs) and with the definitive test for ALPS, defective in vitro Fas-mediated apoptosis. Six of the patients had elevated DNTs, suggestive of ALPS and also had defective Fas-mediated apoptosis. The other 6 patients displayed normal T-cell apoptosis; 5 of whom had normal DNTs, and 1 had a borderline result. Thus, 7 (58%) of 12 patients with ES had elevated DNTs suggestive of ALPS, with functional confirmation in 6 of 7. This suggests that analysis of DNTs may be a sensitive first-line screening test, serving as a marker of patients who should undergo definitive testing for ALPS. Our data further suggest that a number of patients with ES may have ALPS, a novel finding with important therapeutic implications.

  5. Autoimmune lymphoproliferative syndrome (ALPS) caused by Fas (CD95) mutation mimicking sarcoidosis.

    Science.gov (United States)

    Müllauer, Leonhard; Emhofer, Josef; Wohlfart, Sabine; Pichlhöfer, Bettina; Stary, Susanne; Ebetsberger, Georg; Mannhalter, Christine; Chott, Andreas

    2008-02-01

    Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder associated with defects in apoptosis, characterized by childhood onset of lymphadenopathy, splenomegaly, hyperimmunoglobulinemia, and autoimmune disease. ALPS is most frequently associated with a mutation in the cell death receptor Fas (CD95). Very rarely a mutation in caspase 10 is present. An increase of CD4/CD8 double negative T cells in the peripheral blood and lymph nodes is a feature characteristic of ALPS. Additionally, histiocytic proliferations resembling sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) were reported recently in patients with ALPS. In the rare cases with a caspase 10 mutation an accumulation of dendritic cells in lymphoid organs was noted. We describe a different, sarcoidosislike, histiocytic infiltration of lymph nodes that persisted for years in a girl, that was initially supposed to suffer from sarcoidosis, but was eventually diagnosed as ALPS, associated with a missense mutation in the intracellular death domain of Fas. This sarcoidosislike histologic picture extends the spectrum of histiocytic lymph node alterations observed in ALPS and alerts of a potential diagnostic pitfall.

  6. Essential Microenvironment for Thymopoiesis is Preserved in Human Adult and Aged Thymus

    Directory of Open Access Journals (Sweden)

    J. Shiraishi

    2003-01-01

    Full Text Available Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb were employed. One is MoAb to IL-1 receptor (IL-1R recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4+CD8+ double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging.

  7. Increase in CD3+ CD4- T lymphocytes in patients with AIDS and disseminated Mycobacterium avium-intracellulare complex infection: a prospective study. GECSA. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine.

    Science.gov (United States)

    Bonnet, F; Dequae-Merchadou, L; Taupin, J L; Sire, S; Dupon, M; Ragnaud, J M; Lacoste, D; Texier-Maugein, J; Romagné, F; Dabis, F; Pellegrin, J L; Moreau, J F

    1999-08-01

    In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.

  8. Autoimmunity, hypogammaglobulinemia, lymphoproliferation, and mycobacterial disease in patients with activating mutations in STAT3.

    Science.gov (United States)

    Haapaniemi, Emma M; Kaustio, Meri; Rajala, Hanna L M; van Adrichem, Arjan J; Kainulainen, Leena; Glumoff, Virpi; Doffinger, Rainer; Kuusanmäki, Heikki; Heiskanen-Kosma, Tarja; Trotta, Luca; Chiang, Samuel; Kulmala, Petri; Eldfors, Samuli; Katainen, Riku; Siitonen, Sanna; Karjalainen-Lindsberg, Marja-Liisa; Kovanen, Panu E; Otonkoski, Timo; Porkka, Kimmo; Heiskanen, Kaarina; Hänninen, Arno; Bryceson, Yenan T; Uusitalo-Seppälä, Raija; Saarela, Janna; Seppänen, Mikko; Mustjoki, Satu; Kere, Juha

    2015-01-22

    The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of immunodysregulation polyendocrinopathy enteropathy X-linked-like syndrome. Here, we immunologically characterized 3 patients with de novo activating mutations in the DNA binding or dimerization domains of STAT3 (p.K392R, p.M394T, and p.K658N, respectively). The patients displayed multiorgan autoimmunity, lymphoproliferation, and delayed-onset mycobacterial disease. Immunologically, we noted hypogammaglobulinemia with terminal B-cell maturation arrest, dendritic cell deficiency, peripheral eosinopenia, increased double-negative (CD4(-)CD8(-)) T cells, and decreased natural killer, T helper 17, and regulatory T-cell numbers. Notably, the patient harboring the K392R mutation developed T-cell large granular lymphocytic leukemia at age 14 years. Our results broaden the spectrum of phenotypes caused by activating STAT3 mutations, highlight the role of STAT3 in the development and differentiation of multiple immune cell lineages, and strengthen the link between the STAT family of transcription factors and autoimmunity.

  9. Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice.

    Science.gov (United States)

    Dugas, V; Liston, A; Hillhouse, E E; Collin, R; Chabot-Roy, G; Pelletier, A-N; Beauchamp, C; Hardy, K; Lesage, S

    2014-03-01

    Immunoregulatory T cells have been identified as key modulators of peripheral tolerance and participate in preventing autoimmune diseases. CD4(-)CD8(-) (double negative, DN) T cells compose one of these immunoregulatory T-cell subsets, where the injection of DN T cells confers protection from autoimmune diabetes progression. Interestingly, genetic loci defining the function and number of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) coincide with at least some autoimmune disease susceptibility loci. Herein, we investigate the impact of major insulin-dependent diabetes (Idd) loci in defining the number of DN T cells. We demonstrate that although Idd3, Idd5 and Idd9 loci do not regulate DN T-cell number, NOD mice congenic for diabetes resistance alleles at the Idd13 locus show a partial restoration in DN T-cell number. Moreover, competitive and non-competitive bone marrow chimera experiments reveal that DN T-cell number is defined by a bone marrow-intrinsic, but DN T-cell-extrinsic, factor. This suggests that non-autonomous candidate genes define DN T-cell number in secondary lymphoid organs. Together, our results show that the regulation of DN T-cell number in NOD mice is at least partially conferred by alleles at the Idd13 locus.

  10. Negative Concord in Child African American English: Implications for Specific Language Impairment

    Science.gov (United States)

    Coles-White, D'Jaris

    2004-01-01

    In this study, African American English (AAE)-speaking children's comprehension of 2 different types of double negative sentences was examined and contrasted with that of a comparison group of Standard American English (SAE)-speaking children. The first type of double negative, negative concord, involves 2 negative elements in a sentence that are…

  11. Indefinite Determiner Doubling: Data and Methods

    DEFF Research Database (Denmark)

    Wood, Johanna; Vikner, Sten

    2016-01-01

    Syntactic doubling, expressing a constituent twice (or more) when a single occurrence should suffice, is surprisingly common, especially where functional elements are concerned (Barbiers 2008:5). Some well-known examples include multiple negation/negative concord, found in many languages, and dou...

  12. Doubling Down on the PI3K-AKT-mTOR Pathway Enhances the Antitumor Efficacy of PARP Inhibitor in Triple Negative Breast Cancer Model beyond BRCA-ness

    Directory of Open Access Journals (Sweden)

    Pradip De

    2014-01-01

    Full Text Available Phosphoinositide 3-kinase (PI3K pathway, in addition to its pro-proliferative and antiapoptotic effects on tumor cells, contributes to DNA damage repair (DDR. We hypothesized that GDC-0980, a dual PI3K-mammalian target of rapamycin (mTOR inhibitor, would induce an efficient antitumor effect in BRCA-competent triple negative breast cancer (TNBC model when combined with ABT888 and carboplatin. Mechanism-based in vitro studies demonstrated that GDC-0980 treatment alone or in combination led to DNA damage (increased pγH2AXS139; Western blot, immunofluorescence, gain in poly ADP-ribose (PAR, and a subsequent sensitization of BRCA-competent TNBC cells to ABT888 plus carboplatin with a time-dependent 1 decrease in proliferation signals (pAKTT308/S473, pP70S6KT421/S424, pS6RPS235/236, PAR/poly(ADP-ribose polymerase (PARP ratios, PAR/pγH2AX ratios, live/dead cell ratios, cell cycle progression, and three-dimensional clonogenic growths and 2 increase in apoptosis markers (cleaved caspases 3 and 9, a pro-apoptotic BH3-only of Bcl-2 family (BIM, cleaved PARP, annexin V. The combination was effective in vitro in BRCA-wild-type PIK3CA-H1047R-mutated BT20 and PTEN-null HCC70 cells. The combination blocked the growth of established xenograft tumors by 80% to 90% with a concomitant decrease in tumor Ki67, CD31, phosphorylated vascular endothelial growth factor receptor, pS6RPS235/236, and p4EBP1T37/46 as well as an increase in cleaved caspase 3 immunohistochemistry (IHC levels. Interestingly, a combination with GDC-0941, a pan-PI3K inhibitor, failed to block the tumor growth in MDA-MB231. Results demonstrate that the dual inhibition of PI3K and mTOR regulates DDR. In a BRCA-competent model, GDC-0980 enhanced the antitumor activity of ABT888 plus carboplatin by inhibiting both tumor cell proliferation and tumor-induced angiogenesis along with an increase in the tumor cell apoptosis. This is the first mechanism-based study to demonstrate the integral role of the

  13. Micro-syntactic variation in American English Negative Concord

    Directory of Open Access Journals (Sweden)

    Frances Blanchette

    2017-07-01

    Full Text Available This paper presents a series of quantitative gradient acceptability judgment studies of English negative sentences. Adult native speakers of American English recruited via Amazon’s Mechanical Turk were asked to rate sentences on a scale of 1 to 7 on the basis of their naturalness. The main study compares sentences with the marker 'n’t 'and either a negative object (e.g. ‘John didn’t eat nothing’ or a negative subject in canonical position (‘nobody didn’t eat’. Each sentence type has two possible interpretations, one in which the two negatives contribute a single semantic negation, the so-called Negative Concord reading, and another in which the two negations yield a semantic Double Negation logically equivalent to an affirmative. While mean acceptability ratings were below the median for all items, statistical analyses of the gradient data revealed that speakers prefer Negative Concord over Double Negation readings for sentences with negative objects. To rule out a processing explanation for the preference for negative objects over sentence initial negatives, a follow-up study tested the acceptability of sentences with a single negative subject or object and no negative marker. This revealed a preference for subjects, suggesting that the object preference in the two negatives study is a true grammatical effect. A third study revealed that Double Negation constructions are unacceptable overall even in explicit denial contexts, and a fourth study added Negative Auxiliary Inversion constructions (e.g. ‘Didn’t nobody eat’, to compare three types of Negative Concord. The results of all four studies are argued to reveal an English grammar that generates both Negative Concord and Double Negation, and in which Negative Concord is generated despite its unacceptability and reported absence in usage.

  14. Double Conditional Expectation

    Institute of Scientific and Technical Information of China (English)

    HU Di-he

    2004-01-01

    The concept of double conditional expectation is introduced. A series of properties for the double conditional expectation are obtained several convergence theorems and Jensen inequality are proved. Finally we discuss the special cases and application for double conditional expectation.

  15. 自身免疫性淋巴增生综合征一例并文献复习%A case of autoimmune lymphoproliferactive syndrome and literature review

    Institute of Scientific and Technical Information of China (English)

    刘力; 胡坚; 马继军; 李小洁; 李芳芳; 李崇巍

    2014-01-01

    高.治疗以激素和免疫抑制剂为主.%Objective To summarize the clinical characteristics,diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome (ALPS).Method The patient was diagnosed as autoimmune lymphoproliferactive syndrome (ALPS) after being admitted to the Department of Rheumatism and Immunology of Tianjin Children's Hospital in February 20,2014.The clinical characteristics,physical examination,laboratory tests,gene tests,and treatment process were analyzed and related literature was reviewed.Result The patient was a 16-month-old boy.Since the first month of life,he started to have repeatedly fever,diarrhea,shortness of breath,lymphadenopathy,hepatosplenomegaly,anemia(HGBmin 50 g/L) and thrombocytopenia (min 35 × 109/L).But multiple exams showed a normal peripheral blood leukocyte count,hypergammaglobulinemia (IgG 19 800 mg/L,IgA 1 710 mg/L,IgM 2 590 mg/L)and significantly increased serum vitamin B12.Flow cytometric measures showed that CD3 + CD4-CD8-T lymphocytes significantly increased (> 10%) at four times.The count of CD3 + TCRαβ+ CD4-CD8 T lymphocytes (double negative T cells; DNTs) > 3% twice.The genetic test showed that 309th FAS gene area showed heterozygous mutations,the boy was diagnosed as ALPS.Added examinations of lymphocytes apoptosis induced by FAS was positive.He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day,while in maintaining period with normal levels of hemoglobin and platelet,the dose of prednisone was reduced gradually.Till now,the patient has been treated and observed for 8 months.We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years,more than 400 cases reported from foreign countries,but there were only 5 domestic cases.Among those,4 had onset in infancy and 1 at 6-years of age.All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia (4 of them with hemolytic anemia) and

  16. Double-negative metamaterial for mobile phone application

    Science.gov (United States)

    Hossain, M. I.; Faruque, M. R. I.; Islam, M. T.

    2017-01-01

    In this paper, a new design and analysis of metamaterial and its applications to modern handset are presented. The proposed metamaterial unit-cell design consists of two connected square spiral structures, which leads to increase the effective media ratio. The finite instigation technique based on Computer Simulation Technology Microwave Studio is utilized in this investigation, and the measurement is taken in an anechoic chamber. A good agreement is observed among simulated and measured results. The results indicate that the proposed metamaterial can successfully cover cellular phone frequency bands. Moreover, the uses of proposed metamaterial in modern handset antennas are also analyzed. The results reveal that the proposed metamaterial attachment significantly reduces specific absorption rate values without reducing the antenna performances.

  17. The DNA damage- and transcription-associated protein Paxip1 controls thymocyte development and emigration

    DEFF Research Database (Denmark)

    Callen, E.; Faryabi, R.B.; Daniel, Jeremy Austin

    2012-01-01

    Histone 3 lysine 4 trimethylation (H3K4me3) is associated with promoters of active genes and found at hot spots for DNA recombination. Here we have shown that PAXIP1 (also known as PTIP), a protein associated with MLL3 and MLL4 methyltransferase and the DNA damage response, regulates RAG......-mediated cleavage and repair during V(D)J recombination in CD4 CD8 DP thymocytes. Loss of PAXIP1 in developing thymocytes diminished Jα H3K4me3 and germline transcription, suppressed double strand break formation at 3' Jα segments, but resulted in accumulation of unresolved T cell receptor α-chain gene (Tcra...

  18. On Multiplying Negative Numbers.

    Science.gov (United States)

    Crowley, Mary L.; Dunn, Kenneth A.

    1985-01-01

    Comments on the history of negative numbers, some methods that can be used to introduce the multiplication of negative numbers to students, and an explanation of why the product of two negative numbers is a positive number are included. (MNS)

  19. The double identity of linguistic doubling.

    Science.gov (United States)

    Berent, Iris; Bat-El, Outi; Brentari, Diane; Dupuis, Amanda; Vaknin-Nusbaum, Vered

    2016-11-29

    Does knowledge of language consist of abstract principles, or is it fully embodied in the sensorimotor system? To address this question, we investigate the double identity of doubling (e.g., slaflaf, or generally, XX; where X stands for a phonological constituent). Across languages, doubling is known to elicit conflicting preferences at different levels of linguistic analysis (phonology vs. morphology). Here, we show that these preferences are active in the brains of individual speakers, and they are demonstrably distinct from sensorimotor pressures. We first demonstrate that doubling in novel English words elicits divergent percepts: Viewed as meaningless (phonological) forms, doubling is disliked (e.g., slaflaf linguistic preferences doubly dissociate from sensorimotor demands: A single stimulus can elicit diverse percepts, yet these percepts are invariant across stimulus modality--for speech and signs. These conclusions are in line with the possibility that some linguistic principles are abstract, and they apply broadly across language modality.

  20. A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia%利培酮合并知母皂甙元治疗阴性症状为主的精神分裂症的双盲随机对照研究

    Institute of Scientific and Technical Information of China (English)

    肖世富; 薛海波; 李霞; 陈超; 李冠军; 苑成梅; 张明园

    2011-01-01

    Objective To identify whether sarsasapogenin,a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge,would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia.Methods The trial was a double-blind,placebo-controlled,parallelgroup design.The eligible patients were randomized into 2 treatment groups:sarsasapogenin group (sarsasapogenin plus risperidone for 8 weeks,n = 41) and placebo group (risperidone only for 8 weeks,n = 39).At the baseline,as well as at weeks 2,4 and 8 of treatment,the therapeutic response was measured by using scales including Positive and Negative Symptoms Scale (PANSS),Wechsler Memory Scale (WMS),modified Chinese Wechsler Adult Intelligence Scale (mWAIS),Clinical Global Impression (CGI) and Brief Psychiatry Rating Scale (BPRS).The study period for each subject was 8 weeks and duration of overall trial was 2 years.Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS,WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone.The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group.Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia.Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.%目的 探讨知母皂甙元是否能增强利培酮的治疗作用,以及两者联用是否能显著提高阴性症状为主的精神分裂症病人的认知功能.方法 本研究采用双盲、安慰剂对照的平行设计方案.研究对象随机分为知利培酮合并母皂甙组(n= 41)和利培酮合并安慰剂组(n=39

  1. The Cambridge Double Star Atlas

    Science.gov (United States)

    MacEvoy, Bruce; Tirion, Wil

    2015-12-01

    Preface; What are double stars?; The binary orbit; Double star dynamics; Stellar mass and the binary life cycle; The double star population; Detecting double stars; Double star catalogs; Telescope optics; Preparing to observe; Helpful accessories; Viewing challenges; Next steps; Appendices: target list; Useful formulas; Double star orbits; Double star catalogs; The Greek alphabet.

  2. Double outlet right ventricle

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007328.htm Double outlet right ventricle To use the sharing features on this page, please enable JavaScript. Double outlet right ventricle (DORV) is a heart disease that is ...

  3. Chromosome doubling method

    Science.gov (United States)

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  4. Essential role of Rap signal in pre-TCR-mediated beta-selection checkpoint in alphabeta T-cell development.

    Science.gov (United States)

    Kometani, Kohei; Moriyama, Masaki; Nakashima, Yasuhiro; Katayama, Yoshinori; Wang, Shu-Fang; Yamasaki, Sho; Saito, Takashi; Hattori, Masakazu; Minato, Nagahiro

    2008-12-01

    We demonstrate that lck promoter-driven conditional expression of transgenic SPA-1, a Rap GTPase-activation protein, causes a profound defect of alphabeta T-cell development at the CD4/CD8 double-negative (DN) stage due to enhanced cell death without affecting gammadelta T-cell development. The effect was specific to the DN stage, because CD4 promoter-driven SPA-1 expression hardly affected T-cell development. Rap1A17, a dominant-negative Rap mutant, interfered with the generation of double-positive (DP) cells from Rag2(-/-) fetal thymocytes in vitro in the presence of anti-CD3epsilon antibody and Notch ligand. Rap GTPases were activated in a DN cell line by the expression of self-oligomerizing CD3 (CD8:CD3epsilon chimera), which substituted autonomous pre-T-cell receptor (TCR) signal, inducing CD69 expression and CD25 down-regulation. Reciprocally, expression of C3G, a Rap guanine nucleotide exchange factor, in both normal and Rag2(-/-) DN cells markedly enhanced Notch-dependent generation and expansion of DP cells without additional anti-CD3epsilon antibody, thus bypassing pre-TCR. Defective alphabeta T-cell development in the conditional SPA-1-transgenic mice was restored completely by introducing a p53(-/-) mutation. These results suggest that endogenous Rap GTPases downstream of pre-TCR play an essential role in rescuing pre-T cells from the p53-mediated checkpoint response, thus allowing Notch-mediated expansion and differentiation.

  5. 高频重复经颅磁刺激治疗精神分裂症难治性阴性症状的随机双盲对照试验%Effects of high frequency repetitive transcranial magnetic stimulation on refractory negative symptom of schizophrenia: A double blind, randomized controlled trial

    Institute of Scientific and Technical Information of China (English)

    任艳萍; 周东丰; 蔡焯基; 黄青; 卢芩; 陈琦

    2011-01-01

    目的:探讨双背侧前额叶高频重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)治疗精神分裂症难治性阴性症状的疗效和安全性,并观察不良反应.方法:本研究为双盲随机对照临床试验.研究对象来源于2002年11月1日至2003年12月31日期间就诊于北京大学第六医院和北京安定医院的门诊和住院患者,符合美国精神疾病诊断与统计手册第4版(Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition,DSM.IV)中精神分裂症诊断标准.23例以难治性阴性症状为主的精神分裂症患者随机分为rTMS治疗组(n=12)和对照组(n=11),分别给予10次20Hz rTMS真刺激和伪刺激治疗,治疗期间维持原有抗精神病药种类及剂量不变.采用阳性和阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评估临床症状,采用治疗中需处理的不良反应症状量表(Treatment Emergent Symptom scale,TESS)及其他检查评估不良反应.结果:23例患者均完成治疗.治疗组有效率高于对照组(34%vs.17%,P<0.05).未观察到明显不良反应.结论:抗精神病药合并20 Hz双背侧前额叶重复经颅磁刺激治疗精神分裂症难治性阴性症状有效、安全.%Objective: To examine the therapeutic effects of dual dorsolateral prefrontal repetitive transcranial magnetic stimulation ( rTMS ) on refractory negative symptom experienced by patients with schizophrenia. Methods: A double-blind, randomized controlled study was conducted. Totally 23 schizophrenic patients met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia were recruited. Subjects were grouped into active treatment subgroup and sham subgroup randomly. Clinical symptom was measured with the Positive and Negative Symptom Scale (PANSS) . Side effects were valuated with the Treatment Emergent Symptom Scale (TESS). Results: Totally 23 subjects completed the trial. The treatment efficiency of

  6. Immunotoxic effects of cis-urocanic acid exposure in C57BL/6N and C3H/HeN mice.

    Science.gov (United States)

    Prater, M Renee; Gogal, Robert M; De Fabo, Edward C; Longstreth, Janice; Holladay, Steven D

    2003-04-01

    Exposure to ultraviolet radiation results in increased levels of intradermal cis-urocanic acid (cUCA) and alters cutaneous immunity by interfering with processing and presentation of antigen by Langerhans cells. Reports on effects of systemic immunotoxicity with 30 day cUCA exposure in laboratory rodents include thymic atrophy, thymic hypocellularity and decreased T-cell-mediated immunity; however, immune effects of single exposure or 5 day cUCA administration, which may better mimic human exposures, are poorly defined. The present study initially evaluated immune effects of single, 5 day, and 4 week cUCA exposure in C57BL/6N mice. Single administration of intradermal cUCA resulted in decreased splenocyte phagocytosis that persisted for 30 days after cUCA exposure. Five day consecutive cUCA exposure decreased numbers of phenotypically mature CD4(+)CD8(-) and CD4(-)CD8(+) (single positive) thymocytes, increased CD4(+)CD8(+) (double positive) immature thymocytes and increased splenocyte proliferation. Prolonged cUCA exposure (4 weeks) caused profound thymic hypocellularity and splenic hypercellularity and increased splenic macrophage chemiluminescence. Because of this apparent sensitivity of C57BL/6N mice to cUCA, thymic hypocellularity was compared between C57BL/6N and C3H/HeN mice dosed with cUCA, and was found to be more pronounced in the C57BL/6N strain. These results are an extension of previous conclusions on immune modulation caused by cUCA in the spleen and thymus. Further, the observed variation in sensitivity between the mouse strains is consistent with known genetic susceptibility of these strains to the immunomodulatory effects of exposure to sunlight.

  7. Emigration of mature T cells from the thymus is inhibited by the imidazole-based compound 2-acetyl-4-tetrahydroxybutylimidazole.

    Science.gov (United States)

    Gugasyan, R; Coward, A; O'Connor, L; Shortman, K; Scollay, R

    1998-03-01

    The primary role of the thymus is to provide mature T cells for the peripheral immune system. The mechanisms involved in the cellular export processes are as yet unknown. In this study, we examined the ability of 2-acetyl-4-tetrahydroxybutylimidazole (THI), an agent widely used as a component of ammonia caramel food colouring, to inhibit T-cell export from the thymus. BALB/c mice were maintained on drinking water containing THI for 5 days. The mice showed a twofold increase in the total number of mature medullary thymocytes (CD4+CD8- and CD4-CD8+) as well as a slight decrease in the total number of immature double-positive cells (CD4+CD8+). The mature single-positive thymocytes were found to express high levels of the homing molecule L-selectin, suggesting that these potential emigrants were prevented from leaving the thymus. To confirm this, THI-treated mice were injected intrathymically with fluorescein isothiocyanate and the number of labelled T cells appearing in the lymph nodes and spleen was determined 16 hr later. A 10-fold decrease in the number of CD4+ and CD8+ recent thymic emigrants in the lymph nodes and spleen of THI-treated mice was observed. Previous studies have shown that THI does not affect other aspects of thymocyte development, such as proliferation and differentiation. Taken together, these results suggest that the immunosuppressive effects of THI may be due, in part, to preventing of the final step of T-cell export out of the thymus.

  8. Negating the Verum

    DEFF Research Database (Denmark)

    Ørsnes, Bjarne

    2012-01-01

    In Danish the base position of the negation (and negated quantifier phrases) is between the subject and the finite verb in embedded clauses. However, in embedded clauses introduced by a non-veridical complementizer such as hvis ‘if’ or om ‘whether’, the negation can also appear between the comple......In Danish the base position of the negation (and negated quantifier phrases) is between the subject and the finite verb in embedded clauses. However, in embedded clauses introduced by a non-veridical complementizer such as hvis ‘if’ or om ‘whether’, the negation can also appear between...

  9. Negation in English

    Institute of Scientific and Technical Information of China (English)

    宋炳

    2016-01-01

    Every language has its own unique ways of negation and English is no exception. More importance should be attached to when a negative English sentence is translated into its Chinese equivalent. Negation in English can be realized in many differ-ent ways. In the first place, the different types of negation in English will be analyzed. In addition, the affixes and lexicons used to denote negation will be investigated. The last part is mainly concerning the idioms and other expressions which denote nega-tive meanings. In order to make the views much more clearly, some Chinese equivalents of the English sentences will be offered here.

  10. Double layer dynamics in a collisionless magnetoplasma

    DEFF Research Database (Denmark)

    Iizuka, S.; Michelsen, Poul; Juul Rasmussen, Jens

    1985-01-01

    Investigations of double layer dynamics are performed in a Q-machine plasma by applying a positive step potential to a cold end-plate collector. The double layer created at the grounded plasma source just after the pulse is applied propagates towards the collector with the plasma flow speed. Large...... oscillations occur in the plasma current which is related to a recurring formation and propagation of the double layer. The current is limited during the propagation by a growing negative potential dip formed on the low-potential tail. Similar phenomena appear on the low-potential tail of the stationary double...... layer formed by applying a potential difference between two plasma sources...

  11. Psychosexual correlates of sexual double standard endorsement in adolescent sexuality

    NARCIS (Netherlands)

    Emmerink, Peggy; Vanwesenbeeck, Wilhelmina; van den Eijnden, Regina; ter Bogt, Tom

    2016-01-01

    Endorsement and enactment of the (hetero)sexual double standard (SDS), prescribing sexual modesty for girls and sexual prowess for boys, has been shown to be negatively related to sexual and mental health. To be able to challenge the sexual double standard, more insight is needed into the conditions

  12. Psychosexual correlates of sexual double standard endorsement in adolescent sexuality

    NARCIS (Netherlands)

    Emmerink, Peggy; Vanwesenbeeck, Wilhelmina; van den Eijnden, Regina; ter Bogt, Tom

    2016-01-01

    Endorsement and enactment of the (hetero)sexual double standard (SDS), prescribing sexual modesty for girls and sexual prowess for boys, has been shown to be negatively related to sexual and mental health. To be able to challenge the sexual double standard, more insight is needed into the conditions

  13. Experimental study on the inhibitory effect of MSCs on radiation-induced thymoma in mice

    Institute of Scientific and Technical Information of China (English)

    Wen-Long Zhang

    2016-01-01

    Objective:To study the inhibitory effect of MSCs on radiation-induced thymoma in mice. Methods:C57BL/6 mice were selected as the research objects, model group and MSCs group induced thymoma by radiation, and MSCs group received intravenous injection of mesenchymal stem cell for therapy. Six months after treatment, macroscopic morphology of thymus tissue, contents of T lymphocyte subsets as well as expression of tumor suppressor gene PTEN and proliferation marker molecule Ki-67 were detected.Results:(1) macroscopic morphology: thymus tissue weight of model group was significantly greater than that of control group and thymus tissue weight of MSCs group was lower than that of control group; (2) cells and molecules: compared with control group, contents of CD4-CD8-, CD4+CD8- and CD4-CD8+ T cells as well as expression of PTEN in thymus tissue of model group significantly decreased, and CD4+CD8+ T cell content as well as Ki-67 expression significantly increased; compared with model group, contents of CD4-CD8-, CD4+CD8- and CD4-CD8+ T cells as well as expression of PTEN in thymus tissue of MSCs group significantly increased, and CD4+CD8+ T cell content as well as Ki-67 expression significantly decreased.Conclusions:MSCs have inhibitory effect on radiation-induced thymoma in mice, manifested as promoting CD4+CD8- and CD4-CD8+ T cell maturation as well as inhibiting cell proliferation.

  14. Sentential Negation in English

    Science.gov (United States)

    Mowarin, Macaulay

    2009-01-01

    This paper undertakes a detailed analysis of sentential negation in the English language with Chomsky's Government-Binding theory of Transformational Grammar as theoretical model. It distinguishes between constituent and sentential negation in English. The essay identifies the exact position of Negation phrase in an English clause structure. It…

  15. Sentential Negation in English

    Science.gov (United States)

    Mowarin, Macaulay

    2009-01-01

    This paper undertakes a detailed analysis of sentential negation in the English language with Chomsky's Government-Binding theory of Transformational Grammar as theoretical model. It distinguishes between constituent and sentential negation in English. The essay identifies the exact position of Negation phrase in an English clause structure. It…

  16. Comparative analysis of immune activation markers of CD8+ T cells in lymph nodes of different origins in SIV-infected Chinese rhesus macaques

    Directory of Open Access Journals (Sweden)

    Jinbiao Liu

    2016-09-01

    Full Text Available Altered T-cell homeostasis, such as expansion of CD8+ T cells to the secondary lymphatic compartments has been suggested as a mechanism of HIV/SIV-pathogenesis. However, the role of immune activation of CD8+ T cells in the CD4/CD8 turnover and viral replication in these tissues is not completely understood. In the present study, we compared the expression of immune activation markers (CD69 and HLA-DR on CD8+ T cells in the peripheral blood and lymph nodes (LNs of SIV-infected/uninfected Chinese rhesus macaques. SIV-infected macaques had significantly higher percentages of CD8+CD69+ and CD8+HLA-DR+ T cells in all these anatomical compartments than uninfected macaques except for CD8+HLA-DR+ T cells in peripheral blood. LNs that located close to the gastrointestinal (GI tract (colon, mesenteric and iliac LNs of SIV-infected macaques had profoundly lower numbers of CD4+ T cells, but no significantly difference in expression of activation marker (CD8+CD69+ and CD8+HLA-DR+ as compared with the peripheral lymphatic tissues (axillary and inguinal LNs. The CD4/CD8 ratios were negatively correlated with the activation of CD8 T cells in the overall LNs, with further associations with CD8+HLA-DR+ in GI LNs while CD8+CD69+ in peripheral LNs. These observations demonstrate that the increase of CD8+ T cell activation is a contributing factor for the decline of CD4/CD8 ratios in GI system.

  17. Effect of T cell subset and inflammatory cytokine levels on prognosis in patients with pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Cheng-Zhou Wu; Yan-Qiao Wu

    2016-01-01

    Objective:To explore the effect of T cell subset and inflammatory cytokine levels on the prognosis in patients with pulmonary tuberculosis.Methods:A total of 72 patients confirmed with pulmonary tuberculosis who were admitted in our hospital from February, 2013 to February, 2015 were included in the study and served as the experiment group, among which 58 cases had active tuberculosis, and 14 cases had static tuberculosis; while 50 healthy individuals who came for physical examinations were served as the control group. The sputum bacteria before treatment and 6 months after treatment in the two groups were detected. The sputum negative conversion rate was recorded. The absorption of pulmonary lesions and the closure of tuberculosis cavity were examined. The immune cell function of T cell subset was detected again.Results: The peripheral blood CD3, CD4, CD8, and CD4/CD8 levels in the experiment group were significantly lower than those in the control group, especially for the active tuberculosis patients (P<0.01). The peripheral blood CD4/CD8 levels in the static tuberculosis patients was lower than that in the control group, but was significantly higher than that in active tuberculosis patients (P<0.01). The serum IL-1, IL-6, and TNF-α levels in the experiment group were significantly higher than those in the control group, especially for the active tuberculosis patients (P<0.01).Conclusions:The cell subsets and inflammatory cytokines play an important role in patients with pulmonary tuberculosis, whose dynamic change can effectively display the immune function and severity degree, which is of great value in estimating the condition and assessing the prognosis; therefore, it deserves to be further explored in the clinic.

  18. L-forms of H. Pylori

    Institute of Scientific and Technical Information of China (English)

    Ke-Xia Wang; Chao-Pin Li; Yu-Bao Cui; Ye Tian; Qing-Gui Yang

    2003-01-01

    AIM: To study the occurrence of L-forms of H. pyloriinfection in patients with peptic ulcers and its association with possible changes of cellular immune function in the patients.METHODS: Endoscopic biopsy specimens of gastric antrum and gastric corpus were taken from 228 patients with peptic ulcers and inoculated into Skirrow selective medium for H.pylorivegetative forms and special medium for H. pylori Lforms, followed by bacterial isolation and identification. And peripheral venous blood of the patients was taken to detect the percentage of CD3+, CD4+ and CD8+ with biotin-streptavidin (BSA) and the level of IL-2, IL-6 and IL-8 with ElISA.RESULTS: (1) The detection rates of H. pyloriL-forms and vegetative forms in the patients were 50.88 % (116/228)and 64.91 % (148/228) respectively, and the co-infection rate of H. pyloriL-forms and vegetative forms was 78.38 % (116/148). To be more exact, the detection rates of H. pylori L-forms in male and female patients were 57.04 % (77/135) and 41.94 % (39/93) respectively, and statistics found significant difference between them (P<0.05). Furthermore, the detection rates of H. pyloriL-forms in patients aged 14 years-, 30 years-, 40 years- and 50 years- were 31.91%(15/47), 42.86 % (24/56), 56.94 % (41/72) and 67.92 %(36/53) respectively, and there was significant difference between them (P<0.011). (2) The percentages of CD3+, CD4+,CD8+, the ratio of CD4+/CD8+, and the level of IL-2, IL-6,IL-8 in H. pylori-positive patients were (52.59±5.44) %,(35.51±5.74) %, (27.77±8.64) %, (1.56±0.51), (2.66±0.47)mg/L, (108.62±5.85) ng/L and (115.79±7.18) ng/Lrespectively, compared with those in H. pylori-negative patients, the percentages of CD3+, CD4+ and the ratio of CD4+/CD8+ decreased, but the level of IL-2, IL-6 increased, and the difference was significant (P<0.001-P<0.011).Moreover, the percentages of CD3+, CD4+, CD8+, the ratio of CD4+/CD8+, and the level of IL-2, IL-6, IL-8 in the patients with mixed infection of

  19. Unintegrated double parton distributions

    CERN Document Server

    Golec-Biernat, K

    2016-01-01

    We present the construction of unintegrated double parton distribution functions which include dependence on transverse momenta of partons. We extend the formulation which was used to obtain the single unintegrated parton distributions from the standard, integrated parton distribution functions. Starting from the homogeneous part of the evolution equations for the integrated double parton distributions, we construct the unintegrated double parton distributions as the convolutions of the integrated double distributions and the splitting functions, multiplied by the Sudakov form factors. We show that there exist three domains of external hard scales which require three distinct forms of the unintegrated double distributions. The additional transverse momentum dependence which arises through the Sudakov form factors leads to non-trivial correlations in the parton momenta. We also discuss the non-homogeneous contribution to the unintegrated double parton distributions, which arises due to the splitting of a singl...

  20. Nfil3 is a glucocorticoid-regulated gene required for glucocorticoid-induced apoptosis in male murine T cells.

    Science.gov (United States)

    Carey, Kirstyn T; Tan, Kheng H; Ng, Judy; Liddicoat, Douglas R; Godfrey, Dale I; Cole, Timothy J

    2013-04-01

    Glucocorticoids (GCs) have essential roles in the regulation of development, integrated metabolism, and immune and neurological responses, and act primarily via the glucocorticoid receptor (GR). In most cells, GC treatment results in down-regulation of GR mRNA and protein levels via negative feedback mechanisms. However, in GC-treated thymocytes, GR protein levels are maintained at a high level, increasing sensitivity of thymocytes to GCs, resulting in apoptosis termed glucocorticoid-induced cell death (GICD). CD4(+)CD8(+) double-positive thymocytes and thymic natural killer T cells in particular are highly sensitive to GICD. Although GICD is exploited via the use of synthetic GC analogues in the treatment of hematopoietic malignancies, the intracellular molecular pathway of GICD is not well understood. To explore GICD in thymocytes, the authors performed whole genome expression microarray analysis in mouse GR exon 2 null vs wild-type thymus RNA 3 hours after dexamethasone treatment. Identified and validated direct GR targets included P21 and Bim, in addition to an important transcriptional regulator Nfil3, which previously has been associated with GICD and is essential for natural killer cell development in vivo. Immunostaining of NFIL3 in whole thymus localized NFIL3 primarily to the medullary region, and double labeling colocalized NFIL3 to apoptotic cells. In silico analysis revealed a putative GC response element 5 kb upstream of the Nfil3 promoter that is strongly conserved in the rat genome and was confirmed to bind GR by chromatin immunoprecipitation. The knockdown of Nfil3 mRNA levels to 20% of normal using specific small interfering RNAs abrogated GICD, indicating that NFIL3 is required for normal GICD in CTLL-2 T cells.

  1. On Double Vector Bundles

    Institute of Scientific and Technical Information of China (English)

    Zhuo CHEN; Zhang Ju LIU; Yun He SHENG

    2014-01-01

    In this paper, we construct a category of short exact sequences of vector bundles and prove that it is equivalent to the category of double vector bundles. Moreover, operations on double vector bundles can be transferred to operations on the corresponding short exact sequences. In particular, we study the duality theory of double vector bundles in term of the corresponding short exact sequences. Examples including the jet bundle and the Atiyah algebroid are discussed.

  2. On Double Vector Bundles

    OpenAIRE

    Chen, Zhuo; Liu, Zhangju; Sheng, Yunhe

    2011-01-01

    In this paper, we construct a category of short exact sequences of vector bundles and prove that it is equivalent to the category of double vector bundles. Moreover, operations on double vector bundles can be transferred to operations on the corresponding short exact sequences. In particular, we study the duality theory of double vector bundles in term of the corresponding short exact sequences. Examples including the jet bundle and the Atiyah algebroid are discussed.

  3. UNILATERAL INCOMPLETE DOUBLE URETER

    Directory of Open Access Journals (Sweden)

    Kaini

    2013-04-01

    Full Text Available ABSTRACT: Double ureter is a result of premature division of t he ureteric bud. The ureters may join in the lower third of their course and open thr ough a common orifice into the bladder. If they open independently into the bladder, the ureter draining the upper pelvis opens into the bladder below the opening of the other ureter. Patie nts with double ureter or double pelvis are more likely to develop urinary infection and calculi .

  4. Observing Double Stars

    Science.gov (United States)

    Genet, Russell M.; Fulton, B. J.; Bianco, Federica B.; Martinez, John; Baxter, John; Brewer, Mark; Carro, Joseph; Collins, Sarah; Estrada, Chris; Johnson, Jolyon; Salam, Akash; Wallen, Vera; Warren, Naomi; Smith, Thomas C.; Armstrong, James D.; McGaughey, Steve; Pye, John; Mohanan, Kakkala; Church, Rebecca

    2012-05-01

    Double stars have been systematically observed since William Herschel initiated his program in 1779. In 1803 he reported that, to his surprise, many of the systems he had been observing for a quarter century were gravitationally bound binary stars. In 1830 the first binary orbital solution was obtained, leading eventually to the determination of stellar masses. Double star observations have been a prolific field, with observations and discoveries - often made by students and amateurs - routinely published in a number of specialized journals such as the Journal of Double Star Observations. All published double star observations from Herschel's to the present have been incorporated in the Washington Double Star Catalog. In addition to reviewing the history of visual double stars, we discuss four observational technologies and illustrate these with our own observational results from both California and Hawaii on telescopes ranging from small SCTs to the 2-meter Faulkes Telescope North on Haleakala. Two of these technologies are visual observations aimed primarily at published "hands-on" student science education, and CCD observations of both bright and very faint doubles. The other two are recent technologies that have launched a double star renaissance. These are lucky imaging and speckle interferometry, both of which can use electron-multiplying CCD cameras to allow short (30 ms or less) exposures that are read out at high speed with very low noise. Analysis of thousands of high speed exposures allows normal seeing limitations to be overcome so very close doubles can be accurately measured.

  5. Extreme lymphoproliferative disease and fatal autoimmune thrombocytopenia in FasL and TRAIL double-deficient mice.

    Science.gov (United States)

    Sedger, Lisa M; Katewa, Arna; Pettersen, Ann K; Osvath, Sarah R; Farrell, Geoff C; Stewart, Graeme J; Bendall, Linda J; Alexander, Stephen I

    2010-04-22

    To delineate the relative roles of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand in lymphocyte biology and lymphoproliferative disease, we generated mice defective in both molecules. B6.GT mice develop severe polyclonal lymphoproliferative disease because of accumulating CD3(+)CD4(-)CD8(-)B220(+) T cells, CD4(+) and CD8(+) T cells, and follicular B cells, and mice die prematurely from extreme lymphocytosis, thrombocytopenia, and hemorrhage. Accumulating lymphocytes resembled antigen-experienced lymphocytes, consistent with the maximal resistance of B6.GT CD4(+) and CD8(+) T cell to activation-induced cell death. More specifically, we show that TRAIL contributes to Fas ligand-mediated activation-induced cell death and controls lymphocyte apoptosis in the presence of interferon-gamma once antigen stimulation is removed. Furthermore, dysregulated lymphocyte homeostasis results in the production of anti-DNA and rheumatoid factor autoantibodies, as well as antiplatelet IgM and IgG causing thrombocytopenia. Thus, B6.GT mice reveal new roles for TRAIL in lymphocyte homeostasis and autoimmune lymphoproliferative syndromes and are a model of spontaneous idiopathic thrombocytopenia purpura secondary to lymphoproliferative disease.

  6. Double beta decay experiments

    CERN Document Server

    Barabash, A S

    2011-01-01

    The present status of double beta decay experiments is reviewed. The results of the most sensitive experiments are discussed. Proposals for future double beta decay experiments with a sensitivity to the $$ at the level of (0.01--0.1) eV are considered.

  7. Dual doubled geometry

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Riccioni, Fabio; Alvarez-Gaumé, L.

    2011-01-01

    We probe doubled geometry with dual fundamental branes. i.e. solitons. Restricting ourselves first to solitonic branes with more than two transverse directions we find that the doubled geometry requires an effective wrapping rule for the solitonic branes which is dual to the wrapping rule for fundam

  8. CHARACTERISATION OF CELL-MEDIATED IMMUNE RESPONSE IN PIGS IN A CLINICAL CHALLENGE EXPERIMENT OF A VACCINE AGAINST MYCOPLASMA HYOSYNOVIAE

    DEFF Research Database (Denmark)

    Rasmussen, Josephine Skovgaard; Riber, Ulla; Lauritsen, Klara Tølbøll;

    -antigen and recombinant IL-18, significantly higher level of IFN-γ was produced in the vaccine group compared to the placebo group one day before challenge with Mhs. In contrast, significantly higher level of IFN-γ was measured in the placebo group compared to the vaccine group at day 6 after challenge. The latter could...... (Germany) September 10-13, 2009), testing a new vaccine (formalin inactivated Mhs and EMULSIGEN-BCL® (MVP Laboratories)), cell-mediated immune response was measured in the vaccine group (n=13) and not in the placebo group (n=13). In an IFN-γ assay, where whole-blood was co-cultured with Mhs...... to be CD4 and especially CD4CD8 double positive T-cells simultaneously expressing CD25. Interestingly, the proportion of CD4CD8 double positive T-cells within the total population of CD4 positive cells increased in the vaccine group after challenge, indicating that generation of specific T-cell memory had...

  9. CHARACTERISATION OF CELL-MEDIATED IMMUNE RESPONSE IN PIGS IN A CLINICAL CHALLENGE EXPERIMENT OF A VACCINE AGAINST MYCOPLASMA HYOSYNOVIAE

    DEFF Research Database (Denmark)

    Rasmussen, Josephine Skovgaard; Riber, Ulla; Lauritsen, Klara Tølbøll

    (Germany) September 10-13, 2009), testing a new vaccine (formalin inactivated Mhs and EMULSIGEN-BCL® (MVP Laboratories)), cell-mediated immune response was measured in the vaccine group (n=13) and not in the placebo group (n=13). In an IFN-γ assay, where whole-blood was co-cultured with Mhs...... be due to increased systemic infection in the placebo group. Cell-mediated immune response was further characterised by four colour flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) before Mhs challenge (day -1) and at days 6 and 9 after challenge. IFN-γ producing cells were found...... to be CD4 and especially CD4CD8 double positive T-cells simultaneously expressing CD25. Interestingly, the proportion of CD4CD8 double positive T-cells within the total population of CD4 positive cells increased in the vaccine group after challenge, indicating that generation of specific T-cell memory had...

  10. The Analysis of Negative

    Institute of Scientific and Technical Information of China (English)

    辛琨

    2009-01-01

    @@ Chapter 1 The Meaning of Negation Negation,in our daily life,is very commonly used.When you deny something,you use it;when you refuse something,you use it too.And the most common negatiom"no"and"not"are used by US every day.

  11. Topological Quantum Double

    Science.gov (United States)

    Bonneau, Philippe

    Following a preceding paper showing how the introduction of a t.v.s. topology on quantum groups led to a remarkable unification and rigidification of the different definitions, we adapt here, in the same way, the definition of quantum double. This topological double is dualizable and reflexive (even for infinite dimensional algebras). In a simple case we show, considering the double as the "zero class" of an extension theory, the uniqueness of the double structure as a quasi-Hopf algebra. A la suite d'un précédent article montrant comment l'introduction d'une topologie d'e.v.t. sur les groupes quantiques permet une unification et une rigidification remarquables des différentes définitions, on adapte ici de la même manière la définition du double quantique. Ce double topologique est alors dualisable et reflexif (même pour des algèbres de dimension infinie). Dans un cas simple on montre, en considérant le double comme la "classe zéro" d'une théorie d'extensions, l'unicité de cette structure comme algèbre quasi-Hopf.

  12. Study on "double dawn

    Institute of Scientific and Technical Information of China (English)

    刘次沅; 李建科; 周晓陆

    1999-01-01

    The ancient record, "During the first year of King Yi, the day dawned twice at Zheng", has provided important clues to early Chinese chronicles. The astronomical conditions and visible area distributions related to such a "double dawn" event are discussed, and the precision and current problems in the calculations of ancient astronomical phenomena are shown. On such a basis, all the solar eclipses from 1000 BC to 840 BC are calculated and their associated "double dawn" features investigated. The conclusion that the "double dawn" was a solar eclipse occurring on April 21st, 899 BC is corfirmed to be the most reasonable.

  13. Negative thermal expansion

    Energy Technology Data Exchange (ETDEWEB)

    Barrera, G D [Departamento de QuImica, Universidad Nacional de la Patagonia SJB, Ciudad Universitaria, 9000 Comodoro Rivadavia (Argentina); Bruno, J A O [Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de QuImica Inorganica, AnalItica y QuImica FIsica, Pabellon 2, Ciudad Universitaria, 1428 Buenos Aires (Argentina); Barron, T H K [School of Chemistry, University of Bristol, Cantock' s Close, Bristol BS8 1TS (United Kingdom); Allan, N L [School of Chemistry, University of Bristol, Cantock' s Close, Bristol BS8 1TS (United Kingdom)

    2005-02-02

    There has been substantial renewed interest in negative thermal expansion following the discovery that cubic ZrW{sub 2}O{sub 8} contracts over a temperature range in excess of 1000 K. Substances of many different kinds show negative thermal expansion, especially at low temperatures. In this article we review the underlying thermodynamics, emphasizing the roles of thermal stress and elasticity. We also discuss vibrational and non-vibrational mechanisms operating on the atomic scale that are responsible for negative expansion, both isotropic and anisotropic, in a wide range of materials. (topical review)

  14. Toward a Negative Anthropology

    OpenAIRE

    Johannssen, Dennis

    2014-01-01

    Can philosophy say what man is? What is gained or lost by making theoretical assumptions about the human being? This essay examines the “negative anthropology” of the early Frankfurt School by asking how Max Horkheimer, Theodor W. Adorno and Ulrich Sonnemann engage with the question “What is man?” Negative anthropology turns out to be more than the critique of philosophical anthropology: By understanding the human being as the ensemble of what it is not, negative anthropology avoids the predi...

  15. Negative transverse impedance

    Energy Technology Data Exchange (ETDEWEB)

    Chou, W.

    1989-06-12

    Recently, measurements in the SPS show that the coherent tune shift in the horizontal direction has positive values whereas that in the vertical direction has negative ones. Thus the existence of negative transverse impedance gets confirmed in a real machine. This stimulates us to start a new round of systematic studies on this interesting phenomenon. The results obtained from our computer simulations are presented in this note. Our simulations demonstrate that the negative transverse impedance may appear when the rotational symmetry embedded in a discontinuity is broken, and that the geometries that we have studies may be the source of the positive horizontal tune shift measured in the SPS.

  16. Holographic Quantum Entanglement Negativity

    CERN Document Server

    Chaturvedi, Pankaj; Sengupta, Gautam

    2016-01-01

    We propose a holographic prescription to compute the entanglement negativity for conformal field theories at finite temperatures which exactly reproduces the entanglement negativity for (1+1)- dimensional conformal field theories at finite temperatures dual to (2+1)- dimensional bulk Euclidean BTZ black holes. We observe that the holographic entanglement negativity captures the distillable pure quantum entanglement and is related to the holographic mutual information. The application of our prescription to higher dimensional conformal field theories at finite temperatures within a $AdS_{d+1}/CFT_{d}$ scenario involving dual bulk $AdS$-Schwarzschild black holes is discussed to elucidate the universality of our conjecture.

  17. Neutrinoless double beta decay

    Indian Academy of Sciences (India)

    Kai Zuber

    2012-10-01

    The physics potential of neutrinoless double beta decay is discussed. Furthermore, experimental considerations as well as the current status of experiments are presented. Finally, an outlook towards the future, work on nuclear matrix elements and alternative processes is given.

  18. Double conjoining vas deferens.

    Science.gov (United States)

    Gravesen, R G

    1980-03-01

    The importance of careful palpation of the scrotal contents and follow-up semen analysis when performing vasectomies is proved by this case report of a double vas deferens conjoining into a single vas.

  19. Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice.

    Directory of Open Access Journals (Sweden)

    Takashi Izawa

    Full Text Available BACKGROUND: Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF-κB ligand (RANKL-activated dendritic cells (DCs play a key role in the pathogenesis of rheumatoid arthritis (RA in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity. METHODS AND FINDING: Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4(+ T, B, and CD4(-CD8(- double negative (DN T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2 on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice. CONCLUSION: These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice.

  20. On How Fas Apoptosis-Independent Pathways Drive T Cell Hyperproliferation and Lymphadenopathy in lpr Mice.

    Science.gov (United States)

    Balomenos, Dimitrios; Shokri, Rahman; Daszkiewicz, Lidia; Vázquez-Mateo, Cristina; Martínez-A, Carlos

    2017-01-01

    Fas induces massive apoptosis in T cells after repeated in vitro T cell receptor (TCR) stimulation and is critical for lymphocyte homeostasis in Fas-deficient (lpr) mice. Although the in vitro Fas apoptotic mechanism has been defined, there is a large conceptual gap between this in vitro phenomenon and the pathway that leads to in vivo development of lymphadenopathy and autoimmunity. A striking abnormality in lpr mice is the excessive proliferation of CD4(+) and CD8(+) T cells, and more so of the double-negative TCR(+)CD4(-)CD8(-)B220(+) T cells. The basis of lpr T cell hyperproliferation remains elusive, as it cannot be explained by Fas-deficient apoptosis. T cell-directed p21 overexpression reduces hyperactivation/hyperproliferation of all lpr T cell subtypes and lymphadenopathy in lpr mice. p21 controls expansion of repeatedly stimulated T cells without affecting apoptosis. These results confirm a direct link between hyperactivation/hyperproliferation, autoreactivity, and lymphadenopathy in lpr mice and, with earlier studies, suggest that Fas apoptosis-independent pathways control lpr T cell hyperproliferation. lpr T cell hyperproliferation could be an indirect result of the defective apoptosis of repeatedly stimulated lpr T cells. Nonetheless, in this perspective, we argue for an alternative setting, in which lack of Fas would directly cause lpr T cell hyperactivation/hyperproliferation in vivo. We propose that Fas/Fas ligand (FasL) acts as an activation inhibitor of recurrently stimulated T cells, and that its disruption causes overexpansion of T cells in lpr mice. Research to define the underlying mechanism of this Fas/FasL effect could resolve the phenotype of lpr mice and lead to therapeutics for related human syndromes.

  1. Logo and Negative Numbers.

    Science.gov (United States)

    Strawn, Candace A.

    1998-01-01

    Describes LOGO's turtle graphics capabilities based on a sixth-grade classroom's activities with negative numbers and Logo programming. A sidebar explains LOGO and offers suggestions to teachers for using LOGO effectively. (LRW)

  2. Atomic negative ions

    Energy Technology Data Exchange (ETDEWEB)

    Brage, T.

    1991-12-31

    We review some of the recent progress in the studies of alkaline-earth, negative ions. Computations of autodetachment rates, electron affinities and transition wavelengths are discussed and some new and improved results are given.

  3. Atomic negative ions

    Energy Technology Data Exchange (ETDEWEB)

    Brage, T.

    1991-01-01

    We review some of the recent progress in the studies of alkaline-earth, negative ions. Computations of autodetachment rates, electron affinities and transition wavelengths are discussed and some new and improved results are given.

  4. Perisylvian functional connectivity during processing of sentential negation

    Directory of Open Access Journals (Sweden)

    Jörg eBahlmann

    2011-05-01

    Full Text Available Every language has the means to reverse the truth value of a sentence by using specific linguistic markers of negation. In the present study we investigated the neural processing costs afforded by the construction of meaning in German sentences containing negation in different clause types. We studied negations within and across clause boundaries as well as single and double negations. Participants read German sentences comprising of affirmations, single negations in the main or in the subordinate clause, or double negations. As a result, we found a network including the left inferior frontal gyrus (pars triangularis, BA 45, and the left inferior parietal gyrus (BA 40 to be activated whenever negations in the main clause had to be processed. Additionally, we found increased functional coupling between the left pars triangularis (BA 45, left pars opercularis (BA 44, left SMA (BA 6, and left superior temporal gyrus (BA 42 during the processing of main clause negations. The study shows that in order to process negations that require semantic integration across clause boundaries left BA 45 interplays with other areas that have been related to language processing and/or the processing of cognitive demands and logical/conditional reasoning. Thus, the results indicate that the left perisylvian language network synchronizes in order to resolve negations, in particular, whenever requirements on meaning integration are enhanced.

  5. Layered Double Hydroxide as Cordycepin Delivery Nanocarrier

    Institute of Scientific and Technical Information of China (English)

    Qin Zheng YANG; Jing YANG; Chang Kai ZHANG

    2006-01-01

    Layered double hydroxide was investigated as cordycepin delivery nanocarrier for the first time in this study. Negatively charged biomolecule-cordycepin was intercalated in the gallery spaces of [Mg-Al-NO3], which was confirmed by the results of X-ray diffraction and electrophoretic mobility. Cell experiment suggested that the new bio-LDH nanohybrid could prevent cordycepin decomposition by adenosine deaminase. This new formulation could possibly be used as a novel form cordycepin intravenous injection.

  6. The Influence of the Coexpression of CD4 and CD8 in Cutaneous Lesions on Prognosis of Mycosis Fungoides: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Sergio Umberto De Marchi

    2014-01-01

    Full Text Available Background. Although techniques of immunophenotyping have been successful in characterizing the cells in the cutaneous infiltrates of mycosis fungoides little evidence suggests that variations in the phenotypic characterization correlate with prognosis. Objectives. In a preliminary prospective, single-centre, study we correlated the T-cell phenotype in cutaneous biopsies with the progression of the disease to determine whether the coexpression of CD4 and CD8 has an impact on prognosis. Methods. Skin biopsy specimens from 30 newly diagnosed patients were stained with immunoperoxidase techniques to determine their phenotypic characteristics. After a median followup of 42 months patients were divided into two groups with stable and progressive disease. Results. Eighteen patients had the conventional CD4+CD8− T-cell phenotype. Ten patients showed the coexpression of CD4 and CD8 and had a slightly lower rate of progressive disease. Conclusions. The coexpression of CD4 and CD8 in cutaneous lesions is not rare and is associated with a slightly lower rate of progressive disease. Since double positive CD4/CD8 phenotype is rarely reported in mycosis fungoides the presence on conventional immunophenotyping of both CD may be due to a “mixture” of neoplastic cells and inflammatory CD8+ tumor infiltrating lymphocytes. Immunohistochemical study combined with confocal microscopy could clarify this issue.

  7. Vagaries of fluorochrome reporter gene expression in Foxp3+ regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Sonja Schallenberg

    Full Text Available CD4(+CD25(+ regulatory T (Treg cell lineage commitment and expression of the transcription factor Foxp3 can be induced at the CD4(+CD8(+ double-positive (DP and CD4(+CD8(? single-positive stages of thymic development, as well as in postthymic CD4(+ T cells in peripheral lymphoid tissues. The availability of transgenic mice with Foxp3-dependent fluorochrome reporter gene expression has greatly facilitated studies on the intra- and extrathymic generation of murine Foxp3(+ Treg cells. Here, we performed a comparative analysis of thymic Treg cell development and peripheral compartments of mature Treg cells in various transgenic strains with gene targeted and bacterial artificial chromosome (BAC-driven Foxp3-fluorochrome expression. These studies revealed a relative deficiency of Foxp3(+ DP thymocytes selectively in mice with targeted insertion of the fluorochrome reporter gene coding sequence into the endogenous Foxp3 gene. While Foxp3 BAC-driven fluorochrome expression in ex vivo CD4(+ T cells was found to faithfully reflect Foxp3 protein expression, we provide evidence that Foxp3 BAC transgenesis can result in sizable populations of Foxp3(+ Treg cells that lack fluorochrome reporter expression. This could be attributed to both timely delayed up-regulation of BAC expression in developing Treg cells and the accumulation of peripheral Foxp3(+ Treg cells with continuous transcriptional inactivity of the Foxp3 BAC transgene.

  8. Dynamics of Lymphocyte Populations during Trypanosoma cruzi Infection: From Thymocyte Depletion to Differential Cell Expansion/Contraction in Peripheral Lymphoid Organs

    Directory of Open Access Journals (Sweden)

    Alexandre Morrot

    2012-01-01

    Full Text Available The comprehension of the immune responses in infectious diseases is crucial for developing novel therapeutic strategies. Here, we review current findings on the dynamics of lymphocyte subpopulations following experimental acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. In the thymus, although the negative selection process of the T-cell repertoire remains operational, there is a massive thymocyte depletion and abnormal release of immature CD4+CD8+ cells to peripheral lymphoid organs, where they acquire an activated phenotype similar to activated effector or memory T cells. These cells apparently bypassed the negative selection process, and some of them are potentially autoimmune. In infected animals, an atrophy of mesenteric lymph nodes is also observed, in contrast with the lymphocyte expansion in spleen and subcutaneous lymph nodes, illustrating a complex and organ specific dynamics of lymphocyte subpopulations. Accordingly, T- and B-cell activation is seen in subcutaneous lymph nodes and spleen, but not in mesenteric lymph nodes. Lastly, although the function of peripheral CD4+CD8+ T-cell population remains to be defined in vivo, their presence may contribute to the immunopathological events found in both murine and human Chagas disease.

  9. Maternal hematological and virological characteristics during early feline immunodeficiency virus (FIV) infection of cats as predictors of fetal infection and reproductive outcome at early gestation.

    Science.gov (United States)

    Boudreaux, Crystal E; Lockett, Nikki N; Chemerys, Daniellé N; Clay, Brittany T; Scott, Veronica L; Willeford, Bridget; Brown, Timothy; Coats, Karen S

    2009-10-15

    The FIV-infected cat is a small animal model for HIV mother-to-child transmission (MTCT) because the two lentiviruses are biologically related and produce similar clinical syndromes. Both viruses are vertically transmissible and may negatively impact reproductive outcome. Maternal hematological and virological parameters are predictors of MTCT in HIV-infected women. Our purpose was to determine whether similar maternal characteristics during early pregnancy in FIV-infected cats influence pregnancy outcome. We inoculated 10 cats with FIV-B-2542; 10 cats were uninoculated. We quantified longitudinal CD4:CD8 T cell ratios, proviral load, and plasma viremia, monitored longitudinal serostatus, and documented clinical and reproductive outcome during early pregnancy. Inoculated queens were seropositive and provirus positive by week 4 post-infection (p.i.). CD4:CD8 ratios were depressed in the infected group by month 3.5 p.i. Proviral load was variable in the animals throughout the course of infection; plasma viremia was below the level of detection in all animals. Reduced litter sizes and increased fetal demise occurred in infected queens. Viral RNA, but not proviral DNA, was detected in representative placentas (14 of 14; 100%) and fetuses (12 of 14; 86%) collected from infected queens. However, maternal virological and hematological characteristics did not correlate either positively or negatively with reproductive outcome.

  10. Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a signal through thymic shared antigen-1/stem cell antigen-2

    OpenAIRE

    1996-01-01

    During T cell development in the thymus, the expression of thymic shared antigen-1 (TSA-1)/stem cell antigen-2 (Sca-2), a glycosylphosphatidylinositol (GPI)-anchored differentiation antigen, is developmentally regulated. The expression level of TSA-1 is the highest in most immature CD4- CD8- thymocytes, high in CD4+ CD8+ thymocytes, but barely detectable in mature CD4+ CD8- or CD4- CD8- thymocytes and peripheral T cells. We have previously shown that surface TSA-1 expression in peripheral T c...

  11. Nedtrykt af negative nyheder

    DEFF Research Database (Denmark)

    Skovsgaard, Morten; Søberg, Pernille Frantz

    2016-01-01

    I adskillige år er det blevet debatteret, hvorvidt nyhedernes negative fokus har konsekvenser for borgerne, og om det i sid-ste ende får flere til at vende ryggen til nyhederne. Vores viden om effekterne af positive og negative nyheder er dog begrænset, og derfor undersøges det i denne artikel......, hvordan henholdsvis positive og negative tv-nyheder påvirker seernes humør, hukom-melse af information fra indslaget og lyst til at se yderligere tv-nyheder. Det gør vi i et survey-eksperiment (N=204), hvor tre grupper så enten et originalt indslag eller det samme indslag klippet med henholdsvis et...

  12. Covariant holographic entanglement negativity

    CERN Document Server

    Chaturvedi, Pankaj; Sengupta, Gautam

    2016-01-01

    We conjecture a holographic prescription for the covariant entanglement negativity of $d$-dimensional conformal field theories dual to non static bulk $AdS_{d+1}$ gravitational configurations in the framework of the $AdS/CFT$ correspondence. Application of our conjecture to a $AdS_3/CFT_2$ scenario involving bulk rotating BTZ black holes exactly reproduces the entanglement negativity of the corresponding $(1+1)$ dimensional conformal field theories and precisely captures the distillable quantum entanglement. Interestingly our conjecture for the scenario involving dual bulk extremal rotating BTZ black holes also accurately leads to the entanglement negativity for the chiral half of the corresponding $(1+1)$ dimensional conformal field theory at zero temperature.

  13. Polemic and Descriptive Negations

    DEFF Research Database (Denmark)

    Horslund, Camilla Søballe

    2011-01-01

    as such may be more or less central to the meaning of the utterance. The present paper investigates the role of morphosyntactic and prosodic prominence as well as register and social setting on the interpretation of negations. It seems plausible to expect that if the negation as such is central to the meaning...... common in certain social context or genres, while polemic negations are more likely to come up in other genres and social settings. Previous studies have shown a relation between articulatory prominence and register, which may further inform the analysis. Hence, the paper investigates how articulatory...... prominence and register may either work in concert or oppose each other with respect to the cues they provide for the interpretation....

  14. Double layers in a modestly collisional electronegative discharge

    CERN Document Server

    Sheridan, T E

    1999-01-01

    The effect of ion-neutral collisions on the structure and ion flux emanating from a steady-state, planar discharge with two negative components is investigated. The positive ion component is modelled as a cold fluid subject to constant-mobility collisions, while the electrons and negative ions obey Boltzmann relations. The model includes the collisionless limit. When the negative ions are sufficiently cold three types of discharge structures are found. For small negative ion concentrations or high collisionality, the discharge is 'stratified', with an electronegative core and an electropositive edge. For the opposite conditions, the discharge is 'uniform' with the negative ion density remaining significant at the edge of the plasma. Between these cases lies the special case of a double-layer-stratified discharge, where quasi-neutrality is violated at the edge of the electronegative core. Double-layer-stratified solutions are robust in that they persist for moderate collisionality. Numerical solutions for fini...

  15. Negative Probabilities and Contextuality

    CERN Document Server

    de Barros, J Acacio; Oas, Gary

    2015-01-01

    There has been a growing interest, both in physics and psychology, in understanding contextuality in experimentally observed quantities. Different approaches have been proposed to deal with contextual systems, and a promising one is contextuality-by-default, put forth by Dzhafarov and Kujala. The goal of this paper is to present a tutorial on a different approach: negative probabilities. We do so by presenting the overall theory of negative probabilities in a way that is consistent with contextuality-by-default and by examining with this theory some simple examples where contextuality appears, both in physics and psychology.

  16. Project Half Double

    DEFF Research Database (Denmark)

    Ehlers, Michael; Adland, Karoline Thorp; Boston, Nicolai Elborough

    Project Half Double has a clear mission to succeed in finding a project methodology that can increase the success rate of our projects while increasing the speed at which we generate new ideas and develop new products and services. Chaos and complexity should be seen as a basic condition...... and as an opportunity rather than a threat and a risk. We are convinced that by doing so, we can strengthen Denmark’s competitiveness and play an important role in the battle for jobs and future welfare. The overall goal is to deliver “projects in half the time with double the impact”, where projects in half the time...... should be understood as half the time to impact (benefit realisation, effect is achieved) and not as half the time for project execution. The purpose of Project Half Double is to improve Danish industrial competitiveness by radically increasing the pace and impact of the development and innovation...

  17. Double arch mirror study

    Science.gov (United States)

    Vukobratovich, D.; Hillman, D.

    1983-01-01

    The development of a method of mounting light weight glass mirrors for astronomical telescopes compatible with the goals of the Shuttle Infrared Telescope Facility (SIRTF) was investigated. A 20 in. diameter double arch lightweight mirror previously fabricated was modified to use a new mount configuration. This mount concept was developed and fabricated. The mounting concept of the double mounting mirror is outlined. The modifications made to the mirror, fabrication of the mirror mount, and room temperature testing of the mirror and mount and the extension of the mirror and mount concept to a full size (40 in. diameter) primary mirror for SIRTF are discussed.

  18. John Deakin: Double Exposures

    Directory of Open Access Journals (Sweden)

    Paul Rousseau

    2015-11-01

    Full Text Available In this series of short films made by Jonathan Law, the art historian James Boaden, and the curator of The John Deakin Archive, Paul Rousseau, discuss the double-exposure images made by the photographer John Deakin (1912-1972 in the 1950s and 1960s. The films ask you, firstly, to look closely at the images being discussed. Each one begins with a sustained and intense shot of a single image before opening up to a wide-ranging discussion about Deakin, double exposures, and photography.

  19. Double Beta Decay

    CERN Document Server

    Elliott, Steven R

    2011-01-01

    At least one neutrino has a mass of about 50 meV or larger. However, the absolute mass scale for the neutrino remains unknown. Furthermore, the critical question: Is the neutrino its own antiparticle? is unanswered. Studies of double beta decay offer hope for determining the absolute mass scale. In particular, zero-neutrino double beta decay (\\BBz) can address the issues of lepton number conservation, the particle-antiparticle nature of the neutrino, and its mass. A summary of the recent results in \\BBz, and the related technologies will be discussed in the context of the future \\BBz\\ program.

  20. Double-helix stellarator

    Energy Technology Data Exchange (ETDEWEB)

    Moroz, P.E.

    1997-09-01

    A new stellarator configuration, the Double-Helix Stellarator (DHS), is introduced. This novel configuration features a double-helix center post as the only helical element of the stellarator coil system. The DHS configuration has many unique characteristics. One of them is the extreme low plasma aspect ratio, A {approx} 1--1.2. Other advantages include a high enclosed volume, appreciable rotational transform, and a possibility of extreme-high-{beta} MHD equilibria. Moreover, the DHS features improved transport characteristics caused by the absence of the magnetic field ripple on the outboard of the torus. Compactness, simplicity and modularity of the coil system add to the DHS advantages for fusion applications.

  1. Project Half Double

    DEFF Research Database (Denmark)

    Svejvig, Per; Gerstrøm, Anna; Frederiksen, Signe Hedeboe

    The Half Double mission: Project Half Double has a clear mission. We want to succeed in finding a project methodology that can increase the success rate of our projects while increasing the development speed of new products and services. We are convinced that by doing so we can strengthen...... projects and to document their development. The purpose of this addendum is thus to document the development in the pilot projects from June 2016 to January 2017 with particular focus on the impact they have created. This Addendum is a supplement and should be read in conjunction with the Phase 1 report...

  2. Reflection Positive Doubles

    CERN Document Server

    Jaffe, Arthur

    2016-01-01

    Here we introduce reflection positive doubles, a general framework for reflection positivity, covering a wide variety of systems in statistical physics and quantum field theory. These systems may be bosonic, fermionic, or parafermionic in nature. Within the framework of reflection positive doubles, we give necessary and sufficient conditions for reflection positivity. We use a reflection-invariant cone to implement our construction. Our characterization allows for a direct interpretation in terms of coupling constants, making it easy to check in concrete situations. We illustrate our methods with numerous examples.

  3. Depressionens negative spiral

    DEFF Research Database (Denmark)

    Munk, Karen

    2006-01-01

    Artiklen formidler resultater fra en longitudinel undersøgelse af det selvforstærkende, negative samspil imellem udvikling og vedligeholdelse af alderdomsdepression via primære miljøbelastninger og via  den deprimerede ældre som belastning for miljøet, som i sin tur "svarer negativt" på lidelsen og...

  4. The Negative Repetition Effect

    Science.gov (United States)

    Mulligan, Neil W.; Peterson, Daniel J.

    2013-01-01

    A fundamental property of human memory is that repetition enhances memory. Peterson and Mulligan (2012) recently documented a surprising "negative repetition effect," in which participants who studied a list of cue-target pairs twice recalled fewer targets than a group who studied the pairs only once. Words within a pair rhymed, and…

  5. [Lymphocyte subsets, dendritic cells and cytokine profiles in mice with melanoma treated with Uncaria tomentosa].

    Science.gov (United States)

    Lozada-Requena, Iván; Núñez, César; Alvárez, Yubell; Kahn, Laura; Aguilar, José

    2015-10-01

    To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the plant. All cell assays and cytokine measurements were performed by flow cytometry. UT-POA systemically increased CD4/CD8a relation while cell activation was inversely proportional; increased the proportion of DCm; induced a pro-inflammatory Th1 profile and reduced Th17 response. TNF-α and IL-17A positively and negatively correlated with CD4/CD8a relation. The increase of Th1 (TNF-α) may result in the increase of CD4 or M1 macrophage activation. Although UT-POA shows increased DCm, is not dose-dependent. Th17(IL-17A) decreased can support the function of CD8a lymphocytes. UT-POA shows better systemic immunomodulatory effects than intratumoral.

  6. A matterless double slit

    CERN Document Server

    King, B; Keitel, C H; 10.1038/nphoton.2009.261

    2013-01-01

    Double-slits provide incoming photons with a choice. Those that survive the passage have chosen from two possible paths which interfere to distribute them in a wave-like manner. Such wave-particle duality continues to be challenged and investigated in a broad range of disciplines with electrons, neutrons, helium atoms, C60 fullerenes, Bose-Einstein condensates and biological molecules. All variants have hitherto involved material constituents. We present a matterless double-slit scenario in which photons generated from virtual electron-positron pair annihilation in head-on collisions of a probe laser field with two ultra-intense laser beams form a double-slit interference pattern. Such electromagnetic fields are predicted to induce material-like behaviour in the vacuum, supporting elastic scattering between photons. Our double-slit scenario presents on the one hand a realisable method to observe photon-photon scattering, and demonstrates on the other, the possibility of both controlling light with light and n...

  7. The Double Nine Festival

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    THE Double Nine Festival,which falls on theninth day of the ninth lunar month,is anancient tradition among Han Chinese.TheBook of Changes,a famous classic in ancient China,designates the number 9 as yang(the masculine orpositive principle in nature).Thus Double Nine isknown as Chongyang in Chinese,meaning doubleyang.In The Western Capital Miscellancy,Ge Hong(281-341)of the Eastern Jin Dynasty described onetraditional custom of the Western Han Dynasty (206B.C.-A.D.24):″Wearing medicinal comel (Cornusofficinalis),eating double yang cake and drinking chry-santhemum wine on the ninth day of the ninth lunarmonth all help to prolong life.″Therefore the DoubleNine Festival is also celebrated as a festival for the old.People often wear medicinal cornel and climb to ahigh place to drink chrysanthemum wine.The customcomes from a legend:Huan Jing was a student ofnecromancer Fei Changfang in the Eastern Han Dy-nasty (25-220). One day Fei warned Huan that thelatter’s family was in danger of suffering a diaster ont

  8. Chaotic period doubling

    NARCIS (Netherlands)

    Chandramouli, V. V. M. S.; Martens, M.; De Melo, W.; Tresser, C. P.

    2009-01-01

    The period doubling renormalization operator was introduced by Feigenbaum and by Coullet and Tresser in the 1970s to study the asymptotic small-scale geometry of the attractor of one-dimensional systems that are at the transition from simple to chaotic dynamics. This geometry turns out not to depend

  9. Aristotle and Double Effect

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2014-01-01

    There are some interesting similarities between Aristotle’s ‘mixed actions’ in Book III of the Nicomachean Ethics and the actions often thought to be justifiable with the Doctrine of Double Effect. Here I analyse these similarities by comparing Aristotle’s examples of mixed actions with standard ...

  10. Strategies underlying RNA silencing suppression by negative strand RNA viruses

    NARCIS (Netherlands)

    Hemmes, J.C.

    2007-01-01

    The research described in this thesis focused on the strategies of negative strand RNA viruses to counteract antiviral RNA silencing. In plants and insects, RNA silencing has been shown to act as a sequence specific antiviral defence mechanism that is characterised by the processing of double strand

  11. Strategies underlying RNA silencing suppression by negative strand RNA viruses

    NARCIS (Netherlands)

    Hemmes, J.C.

    2007-01-01

    The research described in this thesis focused on the strategies of negative strand RNA viruses to counteract antiviral RNA silencing. In plants and insects, RNA silencing has been shown to act as a sequence specific antiviral defence mechanism that is characterised by the processing of double strand

  12. Negative refractive index and acoustic superlens from multiple scattering in single negative metamaterials.

    Science.gov (United States)

    Kaina, Nadège; Lemoult, Fabrice; Fink, Mathias; Lerosey, Geoffroy

    2015-09-03

    Metamaterials, man-made composite media structured on a scale much smaller than a wavelength, offer surprising possibilities for engineering the propagation of waves. One of the most interesting of these is the ability to achieve superlensing--that is, to focus or image beyond the diffraction limit. This originates from the left-handed behavior--the property of refracting waves negatively--that is typical of negative index metamaterials. Yet reaching this goal requires the design of 'double negative' metamaterials, which act simultaneously on the permittivity and permeability in electromagnetics, or on the density and compressibility in acoustics; this generally implies the use of two different kinds of building blocks or specific particles presenting multiple overlapping resonances. Such a requirement limits the applicability of double negative metamaterials, and has, for example, hampered any demonstration of subwavelength focusing using left-handed acoustic metamaterials. Here we show that these strict conditions can be largely relaxed by relying on media that consist of only one type of single resonant unit cell. Specifically, we show with a simple yet general semi-analytical model that judiciously breaking the symmetry of a single negative metamaterial is sufficient to turn it into a double negative one. We then demonstrate that this occurs solely because of multiple scattering of waves off the metamaterial resonant elements, a phenomenon often disregarded in these media owing to their subwavelength patterning. We apply our approach to acoustics and verify through numerical simulations that it allows the realization of negative index acoustic metamaterials based on Helmholtz resonators only. Finally, we demonstrate the operation of a negative index acoustic superlens, achieving subwavelength focusing and imaging with spot width and resolution 7 and 3.5 times better than the diffraction limit, respectively. Our findings have profound implications for the

  13. Negative magnetoresistivity in holography

    CERN Document Server

    Sun, Ya-Wen

    2016-01-01

    Negative magnetoresistivity is a special magnetotransport property associated with chiral anomaly in four dimensional chiral anomalous systems, which refers to the transport behavior that the DC longitudinal magnetoresistivity decreases with increasing magnetic field. We calculate the longitudinal magnetoconductivity in the presence of backreactions of the magnetic field to gravity in holographic zero charge and axial charge density systems with and without axial charge dissipation. In the absence of axial charge dissipation, we find that the quantum critical conductivity grows with increasing magnetic field when the backreaction strength is larger than a critical value, in contrast to the monotonically decreasing behavior of quantum critical conductivity in the probe limit. With axial charge dissipation, we find the negative magnetoresistivity behavior. The DC longitudinal magnetoconductivity scales as $B$ in the large magnetic field limit, which deviates from the exact $B^2$ scaling of the probe limit resul...

  14. Negative Emissions Technology

    Science.gov (United States)

    Day, Danny

    2006-04-01

    Although `negative emissions' of carbon dioxide need not, in principle, involve use of biological processes to draw carbon out of the atmosphere, such `agricultural' sequestration' is the only known way to remove carbon from the atmosphere on time scales comparable to the time scale for anthropogenic increases in carbon emissions. In order to maintain the `negative emissions' the biomass must be used in such a way that the resulting carbon dioxide is separated and permanently sequestered. Two options for sequestration are in the topsoil and via geologic carbon sequestration. The former has multiple benefits, but the latter also is needed. Thus, although geologic carbon sequestration is viewed skeptically by some environmentalists as simply a way to keep using fossil fuels---it may be a key part of reversing accelerating climate forcing if rapid climate change is beginning to occur. I will first review the general approach of agricultural sequestration combined with use of resulting biofuels in a way that permits carbon separation and then geologic sequestration as a negative emissions technology. Then I discuss the process that is the focus of my company---the EPRIDA cycle. If deployed at a sufficiently large scale, it could reverse the increase in CO2 concentrations. I also estimate of benefits --carbon and other---of large scale deployment of negative emissions technologies. For example, using the EPRIDA cycle by planting and soil sequestering carbon in an area abut In 3X the size of Texas would remove the amount of carbon that is being accumulated worldwide each year. In addition to the atmospheric carbon removal, the EPRIDA approach also counters the depletion of carbon in the soil---increasing topsoil and its fertility; reduces the excess nitrogen in the water by eliminating the need for ammonium nitrate fertilizer and reduces fossil fuel reliance by providing biofuel and avoiding natural gas based fertilizer production.

  15. HER2 expression in Brazilian patients with estrogen and progesterone receptor-negative breast carcinoma.

    Science.gov (United States)

    Ramalho, Susana; Serra, Katia Piton; Vassallo, Jose; Soares, Fernando Augusto; Pinto, Glauce Aparecida; Teixeira, Luiz Carlos; da Cunha, Isabela Werneck; Derchain, Sophie F M; de Souza, Gustavo

    2013-03-01

    The aim of the study was to evaluate the relationship between clinical and pathological factors and survival in patients with double negative HER2-overexpressing carcinoma and triple negative carcinoma. One hundred and sixty-one (161) patients diagnosed with breast cancer negative for estrogen receptor (ER) and progesterone receptor (PR) were included. Of the total, 58 patients had double negative HER2-overexpressing (ER/PR-negative and HER2-positive) and 103 had triple negative (ER-negative, PR-negative and HER2-negative). ER and PR expression was assessed through immunohistochemistry (IHC) and HER2 expression was measured by immunohistochemistry and Fluorescent in situ Hybridization (FISH) analysis in tissue microarray. More than 80% had stages II and III disease and histologic grade III and nuclear grade 3. Patients with triple negative breast carcinoma had undifferentiated histologic types in 11% of cases and vascular invasion in 14.5%. Both groups had more than 50% visceral metastases. HER2 expression (p=0.42) and vascular invasion (p=0.05) did not interfere with survival. Survival of patients with Stages I-II disease was significantly longer than in those with Stage III disease both for double negative HER2-overexpressing carcinomas (p<0.0001) and triple negative carcinomas (p=0.03). The study shows that hormone receptor-negative breast carcinomas were undifferentiated and diagnosed at advanced stages and that HER2 expression was not associated with overall survival.

  16. Double-Skin Facade

    DEFF Research Database (Denmark)

    Kalyanova, Olena

    difficulties experienced by scientists when attempting to model DSF thermal and energy performance were examined. In addition, the lack of experimental studies and empirical validation of models was realized, many numerical models have not been empirically validated and most of them require an expert knowledge...... IEA Annex 34/43, subtask E "Double-Skin Facade". The results of empirical validation are discussed in this work. Discussion and analysis of experimental results is carried out. It has lead to hypothesis of recirculation flow phenomenon in the DSF cavity. Finally, a suggestion of a new numerical model......Double-Skin Facades (DSF) are gaining popularity that, in fact, appears to be independent from sturdy critics of the concept in the past years. DSF buildings are being built in Europe and worldwide, DSF concept is being taught at schools of architecture and fully glazed office buildings are being...

  17. Negative refractive index metamaterials

    Directory of Open Access Journals (Sweden)

    Willie J. Padilla

    2006-07-01

    Full Text Available Engineered materials composed of designed inclusions can exhibit exotic and unique electromagnetic properties not inherent in the individual constituent components. These artificially structured composites, known as metamaterials, have the potential to fill critical voids in the electromagnetic spectrum where material response is limited and enable the construction of novel devices. Recently, metamaterials that display negative refractive index – a property not found in any known naturally occurring material – have drawn significant scientific interest, underscoring the remarkable potential of metamaterials to facilitate new developments in electromagnetism.

  18. Algebra of Majorana doubling.

    Science.gov (United States)

    Lee, Jaehoon; Wilczek, Frank

    2013-11-27

    Motivated by the problem of identifying Majorana mode operators at junctions, we analyze a basic algebraic structure leading to a doubled spectrum. For general (nonlinear) interactions the emergent mode creation operator is highly nonlinear in the original effective mode operators, and therefore also in the underlying electron creation and destruction operators. This phenomenon could open up new possibilities for controlled dynamical manipulation of the modes. We briefly compare and contrast related issues in the Pfaffian quantum Hall state.

  19. Double Cortex Syndrome

    OpenAIRE

    1999-01-01

    The incidence of mutations in the X-linked gene doublecortin in patients with “double cortex” syndrome (DC; also called subcortical band heterotopia or laminar heterotopia) and familial DC with lissencephaly was investigated in a cohort of 8 pedigrees and 47 sporadic patients with DC examined at the Division of Neurogenics, Beth Israel Deaconess Medical Center, Boston, and multiple centers in the US and abroad.

  20. Twisted quantum doubles

    Directory of Open Access Journals (Sweden)

    Daijiro Fukuda

    2004-01-01

    Full Text Available Using diagrammatic pictures of tensor contractions, we consider a Hopf algebra (Aop⊗ℛλA** twisted by an element ℛλ∈A*⊗Aop corresponding to a Hopf algebra morphism λ:A→A. We show that this Hopf algebra is quasitriangular with the universal R-matrix coming from ℛλ when λ2=idA, generalizing the quantum double construction which corresponds to the case λ=idA.

  1. Double-Glazing Interferometry

    OpenAIRE

    Toal, Vincent; Mihaylova, Emilia

    2009-01-01

    This note describes how white light interference fringes can be seen by observing the Moon through a double-glazed window. White light interferometric fringes are normally observed only in a well-aligned interferometer whose optical path difference is less than the coherence length of the light source, which is approximately one micrometer for white light. Obtaining such fringes in a Michelson interferometer is not a trivial task.1 The interferometer is typically illuminated with a monochroma...

  2. Double pendulum contact problem

    Directory of Open Access Journals (Sweden)

    Špička J.

    2014-06-01

    Full Text Available The work concerns contact problems focused on biomechanical systems modelled by a multibody approach. The example is modelling of impact between a body and an infrastructure. The paper firstly presents algorithm for minimum distance calculation. An analytical approach using a tangential plain perpendicular to an initial one is applied. Contact force generated during impact is compared by three different continuous force models, namely the Hertz’s model, the spring-dashpot model and the non-linear damping model. In order to identify contact parameters of these particular models, the method of numerical optimization is used. Purpose of this method is to find the most corresponding results of numerical simulation to the original experiment. Numerical optimization principle is put upon a bouncing ball example for the purpose of evaluation of desirable contact force parameters. The contact modelling is applied to a double pendulum problem. The equation of motion of the double pendulum system is derived using Lagrange equation of the second kind with multipliers, respecting the contact phenomena. Applications in biomechanical research are hinted at arm gravity motion and a double pendulum impact example.

  3. What is Double Parton Scattering?

    CERN Document Server

    Manohar, Aneesh V

    2012-01-01

    Processes such as double Drell-Yan and same-sign WW production have contributions from double parton scattering, which are not well-defined because of a delta(z_\\perp=0) singularity that is generated by QCD evolution. We study the single and double parton contributions to these processes, and show how to handle the singularity using factorization and operator renormalization.

  4. Negative Average Preference Utilitarianism

    Directory of Open Access Journals (Sweden)

    Roger Chao

    2012-03-01

    Full Text Available For many philosophers working in the area of Population Ethics, it seems that either they have to confront the Repugnant Conclusion (where they are forced to the conclusion of creating massive amounts of lives barely worth living, or they have to confront the Non-Identity Problem (where no one is seemingly harmed as their existence is dependent on the “harmful” event that took place. To them it seems there is no escape, they either have to face one problem or the other. However, there is a way around this, allowing us to escape the Repugnant Conclusion, by using what I will call Negative Average Preference Utilitarianism (NAPU – which though similar to anti-frustrationism, has some important differences in practice. Current “positive” forms of utilitarianism have struggled to deal with the Repugnant Conclusion, as their theory actually entails this conclusion; however, it seems that a form of Negative Average Preference Utilitarianism (NAPU easily escapes this dilemma (it never even arises within it.

  5. Negative leave balances

    CERN Multimedia

    Human Resources Department

    2005-01-01

    Members of the personnel entitled to annual leave and, where appropriate, saved leave and/or compensatory leave are requested to take note of the new arrangements described below, which were recommended by the Standing Concertation Committee (SCC) at its meeting on 1Â September 2005 and subsequently approved by the Director-General. The changes do not apply to members of the personnel participating in the Progressive Retirement Programme (PRP) or the Part-time Work as a pre-retirement measure, for whom the specific provisions communicated at the time of joining will continue to apply. Â Negative balances in annual leave, saved leave and/or compensatory leave accounts at the end of the leave year (30th September) and on the date on which bonuses are credited to the saved leave account (31st December): Where members of the personnel have a leave account with a negative balance on 30Â September and/or 31Â December, leave will automatically be transferred from one account to another on the relevant dates i...

  6. Negative leave balances

    CERN Multimedia

    Human Resources Department

    2005-01-01

    Members of the personnel entitled to annual leave and, where appropriate, saved leave and/or compensatory leave are requested to take note of the new arrangements described below, which were recommended by the Standing Concertation Committee (SCC) at its meeting on 1 September 2005 and subsequently approved by the Director-General. The changes do not apply to members of the personnel participating in the Progressive Retirement Programme (PRP) or the Part-time Work as a pre-retirement measure, for whom the specific provisions communicated at the time of joining will continue to apply.  Negative balances in annual leave, saved leave and/or compensatory leave accounts at the end of the leave year (30th September) and on the date on which bonuses are credited to the saved leave account (31st December): Where members of the personnel have a leave account with a negative balance on 30 September and/or 31 December, leave will automatically be transferred from one account to another on the relevant dates in or...

  7. Cosmology With Negative Potentials

    CERN Document Server

    Felder, G; Kofman, L A; Linde, Andrei D; Felder, Gary; Frolov, Andrei; Kofman, Lev; Linde, Andrei

    2002-01-01

    We investigate cosmological evolution in models where the effective potential V(\\phi) may become negative for some values of the field \\phi. Phase portraits of such theories in space of variables (\\phi,\\dot\\phi,H) have several qualitatively new features as compared with phase portraits in the theories with V(\\phi) > 0. Cosmological evolution in models with potentials with a "stable" minimum at V(\\phi)<0 is similar in some respects to the evolution in models with potentials unbounded from below. Instead of reaching an AdS regime dominated by the negative vacuum energy, the universe reaches a turning point where its energy density vanishes, and then it contracts to a singularity with properties that are practically independent of V(\\phi). We apply our methods to investigation of the recently proposed cyclic universe scenario. We show that in addition to the singularity problem there are other problems that need to be resolved in order to realize a cyclic regime in this scenario. We propose several modificati...

  8. Polarized negative ions

    Energy Technology Data Exchange (ETDEWEB)

    Haeberli, W.

    1981-04-01

    This paper presents a survey of methods, commonly in use or under development, to produce beams of polarized negative ions for injection into accelerators. A short summary recalls how the hyperfine interaction is used to obtain nuclear polarization in beams of atoms. Atomic-beam sources for light ions are discussed. If the best presently known techniques are incorporated in all stages of the source, polarized H/sup -/ and D/sup -/ beams in excess of 10 ..mu..A can probably be achieved. Production of polarized ions from fast (keV) beams of polarized atoms is treated separately for atoms in the H(25) excited state (Lamb-Shift source) and atoms in the H(1S) ground state. The negative ion beam from Lamb-Shift sources has reached a plateau just above 1 ..mu..A, but this beam current is adequate for many applications and the somewhat lower beam current is compensated by other desirable characteristics. Sources using fast polarized ground state atoms are in a stage of intense development. The next sections summarize production of polarized heavy ions by the atomic beam method, which is well established, and by optical pumping, which has recently been demonstrated to yield very large nuclear polarization. A short discussion of proposed ion sources for polarized /sup 3/He/sup -/ ions is followed by some concluding remarks.

  9. Colloidal Double Quantum Dots.

    Science.gov (United States)

    Teitelboim, Ayelet; Meir, Noga; Kazes, Miri; Oron, Dan

    2016-05-17

    Pairs of coupled quantum dots with controlled coupling between the two potential wells serve as an extremely rich system, exhibiting a plethora of optical phenomena that do not exist in each of the isolated constituent dots. Over the past decade, coupled quantum systems have been under extensive study in the context of epitaxially grown quantum dots (QDs), but only a handful of examples have been reported with colloidal QDs. This is mostly due to the difficulties in controllably growing nanoparticles that encapsulate within them two dots separated by an energetic barrier via colloidal synthesis methods. Recent advances in colloidal synthesis methods have enabled the first clear demonstrations of colloidal double quantum dots and allowed for the first exploratory studies into their optical properties. Nevertheless, colloidal double QDs can offer an extended level of structural manipulation that allows not only for a broader range of materials to be used as compared with epitaxially grown counterparts but also for more complex control over the coupling mechanisms and coupling strength between two spatially separated quantum dots. The photophysics of these nanostructures is governed by the balance between two coupling mechanisms. The first is via dipole-dipole interactions between the two constituent components, leading to energy transfer between them. The second is associated with overlap of excited carrier wave functions, leading to charge transfer and multicarrier interactions between the two components. The magnitude of the coupling between the two subcomponents is determined by the detailed potential landscape within the nanocrystals (NCs). One of the hallmarks of double QDs is the observation of dual-color emission from a single nanoparticle, which allows for detailed spectroscopy of their properties down to the single particle level. Furthermore, rational design of the two coupled subsystems enables one to tune the emission statistics from single photon

  10. Classroom Management and Negative Reinforcement.

    Science.gov (United States)

    Tauber, Robert T.

    Of the four simple consequences for behavior, none is more misunderstood than negative reinforcement. A Negative Reinforcement Quiz administered to 233 student teachers from two universities revealed that the vast majority of respondents mistakenly viewed negative reinforcement as a synonym for punishment, and believe that negative reinforcement…

  11. On Translation of Negative Sentences

    Institute of Scientific and Technical Information of China (English)

    谭利彬

    2007-01-01

    The English language has its peculiarities in negation.And the method of negation in English is quite different from that in Chinese.In order to fully understand the negative sentence in English,we should make clear the classification and key points of negation first.

  12. On Translation of Negative Sentences

    Institute of Scientific and Technical Information of China (English)

    谭利彬

    2007-01-01

    The English language has its peculiarities in negation. And the method of negation in English is quite different from that in Chinese. In order to fully understand the negative sentence in English, we should make clear the classification and key points of negation first.

  13. Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jing You; Hutcha Sriplung; Alan Geater; Virasakdi Chongsuvivatwong; Lin Zhuang; Hong-Ying Chen; Lan Yu; Bao-Zhang Tang; Jun-Hua Huang

    2008-01-01

    AIM:To investigate peripheral T-lymphocyte subpopulation profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS:Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients.HBV markers were detected with ELISA.Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR).The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS:CHB patients had significantly decreased CD3,and CD4+ cells and CD4+/CD8+ ratio,and increased CD8+ cells compared with uninfected controls (55.44±12.39 vs 71.07±4.76,30.92±7.48 vs 38.94±3.39,1.01±0.49 vs 1.67±0.33,and 34.39±9.22 vs 24.02±4.35;P<0.001,respectively).Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load,presence of serum hepatitis B e antigen (HBeAg) expression,liver disease severity,history of maternal HBV infection,and young age at HBV infection,all with P<0.01.There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P<0.001).There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r=-0.68,-0.65 and-0.75,all P<0.0001),and a positive correlation between CD8+ cells and viral load (r=0.70,P<0.0001).There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P<0.01).In multiple regression (after adjustment for age at HBV infection,maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations,and was the strongest predictor of variation in CD3+,CD4+,CD8+ cells and CD4+/CD8

  14. Primitive Virtual Negative Charge

    CERN Document Server

    Kim, Kiyoung

    2008-01-01

    Physical fields, such as gravity and electromagnetic field, are interpreted as results from rearrangement of vacuum particles to get the equilibrium of net charge density and net mass density in 4-dimensional complex space. Then, both fields should interact to each other in that physical interaction is considered as a field-to-field interaction. Hence, Mass-Charge interaction is introduced with primitive-virtual negative charge defined for the mass. With the concept of Mass-Charge interaction electric equilibrium of the earth is discussed, especially about the electric field and magnetic field of the earth. For unsettled phenomena related with the earth's gravity, such as antigravity phenomenon, gravity anomalies during the solar eclipses, the connection between geomagnetic storms and earthquakes, etc., possible explanations are discussed.

  15. Negative optical torque.

    Science.gov (United States)

    Chen, Jun; Ng, Jack; Ding, Kun; Fung, Kin Hung; Lin, Zhifang; Chan, C T

    2014-09-17

    Light carries angular momentum, and as such it can exert torques on material objects. Applications of these opto-mechanical effects were limited initially due to their smallness in magnitude, but later becomes powerful and versatile after the invention of laser. Novel and practical approaches for harvesting light for particle rotation have since been demonstrated, where the structure is always subjected to a positive optical torque along a certain axis if the incident angular momentum has a positive projection on the same axis. We report here an interesting phenomenon of "negative optical torque", meaning that incoming photons carrying angular momentum rotate an object in the opposite sense. Surprisingly this can be realized quite straightforwardly in simple planar structures. Field retardation is a necessary condition and discrete rotational symmetry of material object plays an important role. The optimal conditions are explored and explained.

  16. The Double Star mission

    Directory of Open Access Journals (Sweden)

    Liu

    2005-11-01

    Full Text Available The Double Star Programme (DSP was first proposed by China in March, 1997 at the Fragrant Hill Workshop on Space Science, Beijing, organized by the Chinese Academy of Science. It is the first mission in collaboration between China and ESA. The mission is made of two spacecraft to investigate the magnetospheric global processes and their response to the interplanetary disturbances in conjunction with the Cluster mission. The first spacecraft, TC-1 (Tan Ce means "Explorer", was launched on 29 December 2003, and the second one, TC-2, on 25 July 2004 on board two Chinese Long March 2C rockets. TC-1 was injected in an equatorial orbit of 570x79000 km altitude with a 28° inclination and TC-2 in a polar orbit of 560x38000 km altitude. The orbits have been designed to complement the Cluster mission by maximizing the time when both Cluster and Double Star are in the same scientific regions. The two missions allow simultaneous observations of the Earth magnetosphere from six points in space. To facilitate the comparison of data, half of the Double Star payload is made of spare or duplicates of the Cluster instruments; the other half is made of Chinese instruments. The science operations are coordinated by the Chinese DSP Scientific Operations Centre (DSOC in Beijing and the European Payload Operations Service (EPOS at RAL, UK. The spacecraft and ground segment operations are performed by the DSP Operations and Management Centre (DOMC and DSOC in China, using three ground station, in Beijing, Shanghai and Villafranca.

  17. Magnetism in Re-based ferrimagnetic double perovskites

    Science.gov (United States)

    Winkler, A.; Narayanan, N.; Mikhailova, D.; Bramnik, K. G.; Ehrenberg, H.; Fuess, H.; Vaitheeswaran, G.; Kanchana, V.; Wilhelm, F.; Rogalev, A.; Kolchinskaya, A.; Alff, L.

    2009-07-01

    We have investigated spin and orbital magnetic moments of the Re 5d ion in the double perovskites A2FeReO6 (A=Ba, Sr, Ca) by x-ray magnetic circular dichroism (XMCD) at the Re L2, 3 edges. In these ferrimagnetic compounds, an unusually large negative spin and positive orbital magnetic moment at the Re atoms was detected. The presence of a finite spin magnetic moment in a 'non-magnetic' double perovskite as observed in the double perovskite Sr2ScReO6 proves that Re has also a small, but finite intrinsic magnetic moment. We further show for the examples of Ba and Ca that the usually neglected alkaline earth ions undoubtedly also contribute to the magnetism in the ferrimagnetic double perovskites.

  18. Magnetism in Re-based ferrimagnetic double perovskites

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, A; Narayanan, N; Mikhailova, D; Bramnik, K G; Ehrenberg, H; Fuess, H; Kolchinskaya, A; Alff, L [Technische Universitaet Darmstadt, Petersenstrasse 23, 64287 Darmstadt (Germany); Vaitheeswaran, G; Kanchana, V [Royal Institute of Technology (KTH), Brinellvaegen 23, 10044 Stockholm (Sweden); Wilhelm, F; Rogalev, A [European Synchrotron Radiation Facility (ESRF), 6 Rue Jules Horowitz, BP 220, 38043 Grenoble Cedex 9 (France)], E-mail: alff@oxide.tu-darmstadt.de

    2009-07-15

    We have investigated spin and orbital magnetic moments of the Re 5d ion in the double perovskites A{sub 2}FeReO{sub 6} (A=Ba, Sr, Ca) by x-ray magnetic circular dichroism (XMCD) at the Re L{sub 2,3} edges. In these ferrimagnetic compounds, an unusually large negative spin and positive orbital magnetic moment at the Re atoms was detected. The presence of a finite spin magnetic moment in a 'non-magnetic' double perovskite as observed in the double perovskite Sr{sub 2}ScReO{sub 6} proves that Re has also a small, but finite intrinsic magnetic moment. We further show for the examples of Ba and Ca that the usually neglected alkaline earth ions undoubtedly also contribute to the magnetism in the ferrimagnetic double perovskites.

  19. A Biochemical Double Slit

    Science.gov (United States)

    Kominis, Iannis

    2011-03-01

    Radical-ion-pair reactions, fundamental in photosynthesis and at the basis of the avian magnetic compass mechanism, have been recently shown to offer a rich playground for applying methods and concepts from quantum measurement/quantum information science. We will demonstrate that radical-ion-pair reactions are almost the exact analog of the optical double slit experiment, i.e. Nature has already engineered biochemical reactions performing the act of quantum interference. We will further elaborate on the non-trivial quantum effects pertaining in these reactions and the recent debate on their fundamental theoretical description that these effects have sparked.

  20. Negative Expertise: Comparing Differently Tenured Elder Care Nurses' Negative Knowledge

    Science.gov (United States)

    Gartmeier, Martin; Lehtinen, Erno; Gruber, Hans; Heid, Helmut

    2011-01-01

    Negative expertise is conceptualised as the professional's ability to avoid errors during practice due to certain cognitive agencies. In this study, negative knowledge (i.e. knowledge about what is wrong in a certain context and situation) is conceptualised as one such agency. This study compares and investigates the negative knowledge of elder…

  1. Large negative lateral shifts due to negative refraction

    CERN Document Server

    Benedicto, Jessica; Moreau, Antoine; Centeno, Emmanuel

    2011-01-01

    When a thin structure in which negative refraction occurs (a metallo-dielectric or a photonic crystal) is illuminated by a beam, the reflected and transmitted beam can undergo a large negative lateral shift. This phenomenon can be seen as an interferential enhancement of the geometrical shift and can be considered as a signature of negative refraction.

  2. Firewalls From Double Purity

    CERN Document Server

    Bousso, Raphael

    2013-01-01

    The firewall paradox is often presented as arising from double entanglement, but I argue that more generally the paradox is double purity. Near-horizon modes are purified by the interior, in the infalling vacuum. Hence they cannot also be pure alone, or in combination with any third system, as demanded by unitarity. This conflict arises independently of the Page time, for entangled and for pure states. It implies that identifications of Hilbert spaces cannot resolve the paradox. Traditional complementarity requires the unitary identification of infalling matter with a scrambled subsystem of the Hawking radiation. Extending this map to the infalling vacuum overdetermines the out-state. More general complementarity maps ("A=R_B", "ER=EPR") founder when the near-horizon zone is pure. I argue that pure-zone states span the microcanonical ensemble, and that this suffices to make the horizon a special place. I advocate that the ability to detect the horizon locally, rather than the degree or probability of violence...

  3. Coagulase-Negative Staphylococci

    Science.gov (United States)

    Heilmann, Christine; Peters, Georg

    2014-01-01

    SUMMARY The definition of the heterogeneous group of coagulase-negative staphylococci (CoNS) is still based on diagnostic procedures that fulfill the clinical need to differentiate between Staphylococcus aureus and those staphylococci classified historically as being less or nonpathogenic. Due to patient- and procedure-related changes, CoNS now represent one of the major nosocomial pathogens, with S. epidermidis and S. haemolyticus being the most significant species. They account substantially for foreign body-related infections and infections in preterm newborns. While S. saprophyticus has been associated with acute urethritis, S. lugdunensis has a unique status, in some aspects resembling S. aureus in causing infectious endocarditis. In addition to CoNS found as food-associated saprophytes, many other CoNS species colonize the skin and mucous membranes of humans and animals and are less frequently involved in clinically manifested infections. This blurred gradation in terms of pathogenicity is reflected by species- and strain-specific virulence factors and the development of different host-defending strategies. Clearly, CoNS possess fewer virulence properties than S. aureus, with a respectively different disease spectrum. In this regard, host susceptibility is much more important. Therapeutically, CoNS are challenging due to the large proportion of methicillin-resistant strains and increasing numbers of isolates with less susceptibility to glycopeptides. PMID:25278577

  4. MELATONIN AND IMMUNOMODULATION IN AGED AND IMMUNODEFICIENT MICE

    Institute of Scientific and Technical Information of China (English)

    周爱民; 袁育康; 范桂香

    2003-01-01

    Objective To investigate melatonin-related mechanisms of action on immunoregulation in aged and immunodeficient mice. Methods T lymPhocytes subunit CD4+,CD8+ and CD4+/CD8+ ratio were measured by Flow Cytometer in normal, aged and Cyclophosphamide injected mice which treated with melatonin, and compared with the results of T lymphocytes subunit in the group without melatonin as control group. Results The percentage of CD4+, CD8+ T cells in the normal mice which treated with melatonin was significantly higher than that in control group (P<0.01), CD4+/CD8+ ratio was higher but had no significant difference. In the cyclophosphamide injected group which melatonin treated, the percentage of CD4+ T cells and CD4+/CD8+ ratio were higher than those in control, The difference was significant (P<0.01), while CD8+ was lower (P<0.01). In aged melatonin treated mice group, the percentage of CD4+, CD8+ T cells and CD4+/CD8+ ratio were significantly higher than those in control (P<0.01). Conclusion Melatonin could adjust the quantity and the ratio of CD4+, CD8+ T cells in aged and immunodeficient mice. it implied that melatonin could mediate helper and suppression T lymphocytes to reinforce their immunodefence.

  5. Negative Refraction at Visible Frequencies

    National Research Council Canada - National Science Library

    Henri J. Lezec; Jennifer A. Dionne; Harry A. Atwater

    2007-01-01

    .... We demonstrate an experimental realization of a two-dimensional negative-index material in the blue-green region of the visible spectrum, substantiated by direct geometric visualization of negative refraction...

  6. Foxp3(+) regulatory T cells are increased in the early stages of halo nevi: clinicopathological features of 30 halo nevi.

    Science.gov (United States)

    Park, H S; Jin, S A; Choi, Y-D; Shin, M-H; Lee, S E; Yun, S J

    2012-01-01

    There have been few clinical studies of the role of regulatory T cells (Tregs) in halo formation of halo nevus. To evaluate the clinicopathologic features and the presence of Tregs in halo nevi. We analyzed 30 halo nevi and performed immunohistochemical analysis using antibodies against CD4, CD8, CD25 and Foxp3. We also performed double immunohistochemical staining for Foxp3 and CD25. We found significant increases in Foxp3(+) Tregs, and the shorter the halo nevus duration, the more Foxp3(+) Tregs were detected. Also, the ratio of Foxp3 to CD8 T cells was increased in early stages of halo nevi. Double immunohistochemical staining suggested that the Tregs in the halo nevi were CD25(+)Foxp3(+) T cells. Foxp3(+) Tregs were greatly increased in the halo nevi. The shorter the halo nevi duration, the more Foxp3(+) Tregs were involved in the earlier developmental stages of halo nevi. Copyright © 2012 S. Karger AG, Basel.

  7. Double Field Theory Inspired Cosmology

    CERN Document Server

    Wu, Houwen

    2014-01-01

    Double field theory proposes a generalized spacetime action possessing manifest T-duality on the level of component fields. We calculate the cosmological solutions of double field theory with vanishing Kalb-Ramond field. It turns out that double field theory provides a more consistent way to construct cosmological solutions than the standard string cosmology. We find two sets of solutions in double field theory cosmology, respecting or violating the strong (weak) constraint. Both sets of solutions naturally contain the pre- and post-big bang evolutions in one single line element. This novel feature opens a window for possible resolution of the cosmic amnesia. We also demonstrate that the scale factor duality in the standard string cosmology is nothing but the T-duality in double field theory. The scale dual dilatons in the standard string cosmology is simply the usual diffeomorphic scalar dilaton $\\phi$ and dual diffeomorphic scalar dilaton $\\tilde\\phi$ in double field theory. Furthermore, we identify the "sh...

  8. The case for negative senescence

    DEFF Research Database (Denmark)

    Vaupel, James W; Baudisch, Annette; Dölling, Martin

    2004-01-01

    kinds of animals that may experience negative senescence and conclude that negative senescence may be widespread, especially in indeterminate-growth species for which size and fertility increase with age. We develop optimization models of life-history strategies that demonstrate that negative senescence...

  9. Counting Irreducible Double Occurrence Words

    CERN Document Server

    Burns, Jonathan

    2011-01-01

    A double occurrence word $w$ over a finite alphabet $\\Sigma$ is a word in which each alphabet letter appears exactly twice. Such words arise naturally in the study of topology, graph theory, and combinatorics. Recently, double occurrence words have been used for studying DNA recombination events. We develop formulas for counting and enumerating several elementary classes of double occurrence words such as palindromic, irreducible, and strongly-irreducible words.

  10. Colored Flag by Double Refraction.

    Science.gov (United States)

    Reid, Bill

    1994-01-01

    Describes various demonstrations that illustrate double refraction and rotation of the plane of polarization in stressed, transparent plastics, with the consequent production of colored designs. (ZWH)

  11. Double Degenerate Stars

    Institute of Scientific and Technical Information of China (English)

    LUO Xin-Lian; BAI Hua; ZHAO Lei

    2008-01-01

    Regardless of the formation mechanism, an exotic object, the double degenerate star (DDS), is introduced and investigated, which is composed of baryonic matter and some unknown fermion dark matter. Different from the simple white dwarfs (WDs), there is additional gravitational force provided by the unknown fermion component inside DDSs, which may strongly affect the structure and the stability of such kind of objects. Many possible and strange observational phenomena connecting with them are concisely discussed. Similar to the normal WD, this object can also experience thermonuclear explosion as type Ia supernova explosion when DDS's mass exceeds the maximum mass that can be supported by electron degeneracy pressure. However, since the total mass of baryonic matter can be much lower than that of WD at Chandrasekhar mass limit, the peak luminosity should be much dimmer than what we expect before, which may throw a slight shadow on the standard candle of SN Ia in the research of cosmology.

  12. GENERALIZED DOUBLE PARETO SHRINKAGE.

    Science.gov (United States)

    Armagan, Artin; Dunson, David B; Lee, Jaeyong

    2013-01-01

    We propose a generalized double Pareto prior for Bayesian shrinkage estimation and inferences in linear models. The prior can be obtained via a scale mixture of Laplace or normal distributions, forming a bridge between the Laplace and Normal-Jeffreys' priors. While it has a spike at zero like the Laplace density, it also has a Student's t-like tail behavior. Bayesian computation is straightforward via a simple Gibbs sampling algorithm. We investigate the properties of the maximum a posteriori estimator, as sparse estimation plays an important role in many problems, reveal connections with some well-established regularization procedures, and show some asymptotic results. The performance of the prior is tested through simulations and an application.

  13. Dual Double Field Theory

    CERN Document Server

    Bergshoeff, Eric A; Penas, Victor A; Riccioni, Fabio

    2016-01-01

    We present the dual formulation of double field theory at the linearized level. This is a classically equivalent theory describing the duals of the dilaton, the Kalb-Ramond field and the graviton in a T-duality or O(D,D) covariant way. In agreement with previous proposals, the resulting theory encodes fields in mixed Young-tableau representations, combining them into an antisymmetric 4-tensor under O(D,D). In contrast to previous proposals, the theory also requires an antisymmetric 2-tensor and a singlet, which are not all pure gauge. The need for these additional fields is analogous to a similar phenomenon for "exotic" dualizations, and we clarify this by comparing with the dualizations of the component fields. We close with some speculative remarks on the significance of these observations for the full non-linear theory yet to be constructed.

  14. Analysis of plasma distribution near the extraction region in surface produced negative ion sources.

    Science.gov (United States)

    Fukano, A; Hatayama, A

    2014-02-01

    In study of a negative ion source, it is important to understand the plasma characteristics near the extraction region. A recent experiment in the NIFS-R&D ion source has suggested that a "double ion plasma layer" which is a region consisting of hydrogen positive and negative ions exists near the plasma grid (PG). Density distribution of plasma near the extraction region is studied analytically. It is shown that the density distribution depends on an amount of the surface produced negative ions and the double ion plasma layer is formed near the PG surface for the case of strong surface production.

  15. Negative ions in liquid helium

    Science.gov (United States)

    Khrapak, A. G.; Schmidt, W. F.

    2011-05-01

    The structure of negative ions in liquid 4He is analyzed. The possibility of cluster or bubble formation around impurity ions of both signs is discussed. It is shown that in superfluid helium, bubbles form around negative alkaline earth metal ions and clusters form around halogen ions. The nature of "fast" and "exotic" negative ions is also discussed. It is assumed that "fast" ions are negative ions of helium excimer molecules localized inside bubbles. "Exotic" ions are stable negative impurity ions, which are always present in small amounts in gas discharge plasmas. Bubbles or clusters with radii smaller the radius of electron bubbles develop around these ions.

  16. Negative refraction realized by band folding effect in resonator-based acoustic metamaterials

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jiao; Hou, Zhilin, E-mail: phzlhou@scut.edu.cn; Fu, Xiujun

    2015-09-25

    We show in the paper that a two-dimensional acoustic metamaterial with isotropic negative refraction band at subwavelength scale can be constructed simply by arranging only one kind of Helmholtz resonators into honeycomb-like lattice. To understand the phenomenon, the mechanism for double negative metamaterial is investigated. We point out that double negative metamaterials can be obtained only when the phase accumulating over their constructive unit cell becomes greater than π but smaller than 2π. Based on the understanding, we attribute the negative refraction phenomenon in our suggested structure as a result of the band folding effect. - Highlights: • Negative-refraction structure by only one kind of resonators is suggested. • Directional and isotropic negative band at subwavelength scale are obtained. • The mechanism is understood as the band folding effect. • The influences of the wall friction and thermoviscous diffusive effect are checked.

  17. Broadband negative refractive index obtained by plasmonic hybridization in metamaterials

    Science.gov (United States)

    Nguyen, Hien T.; Bui, Tung S.; Yan, Sen; Vandenbosch, Guy A. E.; Lievens, Peter; Vu, Lam D.; Janssens, Ewald

    2016-11-01

    We experimentally demonstrate a broadband negative refractive index (NRI) behavior in combined dimer and fishnet dimer metamaterials operating in the GHz frequency range. The observations can be well explained by a hybridization model and are in agreement with numerical modelling results. Hybridization of the magnetic resonances is obtained by reducing the distance between the layers in the dimer structures. A ratio of the double negative refractive index bandwidth to operational frequency of approximately 10% was achieved in the fishnet dimer. The applicable frequency range of the broadband NRI was shown to scale with the size of the structures from the microwave to the far infrared.

  18. Merging Nonlinear Optics and Negative-Index Metamaterials

    CERN Document Server

    Popov, Alexander K

    2011-01-01

    The extraordinary properties of nonlinear optical propagation processes in double-domain positive/negative index metamaterials are reviewed. These processes include second harmonic generation, three- and four-wave frequency mixing, and optical parametric amplification. Striking contrasts with the properties of the counterparts in ordinary materials are shown. We also discuss the possibilities for compensating strong losses inherent to plasmonic metamaterials, which present a major obstacle in numerous exciting applications, and the possibilities for creation of unique ultracompact photonic devices such as data processing chips and nonlinear-optical sensors. Finally, we propose similar extraordinary three-wave mixing processes in crystals based on optical phonons with negative dispersion.

  19. Negative selection of murine medullary-type single positive thymocytes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Negative selection depletes self-reactive T cells, thus ensuring self-tolerance. It is usually considered that negative selection imposed on double-positive (DP) thymocytes that reside at the cortico-medullary junction. Negative selection model was set up by injecting mice with anti-T cell receptor (TCR) monoclonal antibody (mAb) intraperitoneally in this work. As shown in phenotypic analysis of thymocytes, negative selection destroys not only cortical-type DP thymocytes, but also medullary-type CD3+TCRαβ+CD4SP and CD3+TCRαβ+CD8SP thymocytes. Negative selection of medullary-type single positive (SP) are more susceptible to apoptosis, while with development of the cells, their resistance to apoptosis increases. Therefore, negative selection does not operate on functionally mature thymocytes at the late stage. This result is a supplement to the traditional theory of negative selection. Negative selection of medullary-type thymocytes is probably to further deplete self-reactive T cells, thus producing precise TCR repertoire and inducing self-tolerance.

  20. The negation bias: when negations signal stereotypic expectancies.

    Science.gov (United States)

    Beukeboom, Camiel J; Finkenauer, Catrin; Wigboldus, Daniël H J

    2010-12-01

    Research on linguistic biases shows that stereotypic expectancies are implicitly reflected in language and are thereby subtly communicated to message recipients. We examined whether these findings extend to the use of negations (e.g., not smart instead of stupid). We hypothesized that people use more negations in descriptions of stereotype-inconsistent behavior than in descriptions of stereotype-consistent behavior. In 3 studies, participants either judged the applicability of experimentally controlled person descriptions or spontaneously produced person descriptions themselves. Results provided support for this hypothesis. Moreover, a 4th study demonstrated that negations have communicative consequences. When a target person's behavior was described with negations, message recipients inferred that this behavior was an exception to the rule and that it was more likely caused by situational circumstances than by dispositional factors. These findings indicate that by using negations people implicitly communicate stereotypic expectancies and that negations play a subtle but powerful role in stereotype maintenance.

  1. Negative snakes in JET: evidence for negative shear

    Energy Technology Data Exchange (ETDEWEB)

    Gill, R.D.; Alper, B.; Edwards, A.W. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Pearson, D. [Reading Univ. (United Kingdom)

    1994-07-01

    The signature of the negative snakes from the soft X-ray cameras is very similar to the more usual snakes except that the localised region of the snake has, compared with its surroundings, decreased rather than increased emission. Circumstances where negative snakes have been seen are reviewed. The negative snake appears as a region of increased resistance and of increased impurity density. The relationship between the shear and the current perturbation is shown, and it seem probable that the magnetic shear is reversed at the point of the negative snake, i.e. that q is decreasing with radius. 6 refs., 6 figs.

  2. Compound negative binomial distribution with negative multinomial summands

    Science.gov (United States)

    Jordanova, Pavlina K.; Petkova, Monika P.; Stehlík, Milan

    2016-12-01

    The class of Negative Binomial distributions seems to be introduced by Greenwood and Yule in 1920. Due to its wide spread application, investigations of distributions, closely related with it will be always contemporary. Bates, Neyman and Wishart introduce Negative Multinomial distribution. They reach it considering the mixture of independent Poisson distributed random variables with one and the same Gamma mixing variable. This paper investigates a particular case of multivariate compound distribution with one and the same compounding variable. In our case it is Negative Binomial or Sifted Negative Binomial. The summands with equal indexes in different coordinates are Negative Multinomially distributed. In case without shifting, considered as a mixture, the resulting distribution coincides with Mixed Negative Multinomial distribution with scale changed Negative Binomially distributed first parameter. We prove prove that it is Multivariate Power Series Distributed and find explicit form of its parameters. When the summands are geometrically distributed this distribution is stochastically equivalent to a product of independent Bernoulli random variable and appropriate multivariate Geometrically distributed random vector. We show that Compound Shifted Negative Binomial Distribution with Geometric Summands is a particular case of Negative Multinomial distribution with new parameters.

  3. Plasmonic resonances in optomagnetic metamaterials based on double dot arrays.

    Science.gov (United States)

    Kravets, Vasyl G; Schedin, Fred; Taylor, Shaun; Viita, David; Grigorenko, Alexander N

    2010-05-10

    We study optical properties of optomagnetic metamaterials produced by regular arrays of double gold dots (nanopillars). Using combined data of spectroscopic ellipsometry, transmission and reflection measurements, we identify localized plasmon resonances of a nanopillar pair and measure their dependences on dot sizes. We formulate the necessary condition at which an effective field theory can be applied to describe optical properties of a composite medium and employ interferometry to measure phase shifts for our samples. A negative phase shift for transmitted green light coupled to an antisymmetric magnetic mode of a double-dot array is observed. (c) 2010 Optical Society of America.

  4. Nonsyndromic double mesiodentes- hidden lambs among normal flock!

    Science.gov (United States)

    Gharote, Harshkant P; Nair, Preeti P; Thomas, Shaji; R, Guru Prasad; Singh, Shikha

    2011-01-01

    Mesiodens, a common supernumerary tooth, is found in the midline in anterior maxilla between the incisors. Its occurrence as multiples is termed as ‘mesiodentes’. Double mesiodentes, a rare phenomenon, is seldom reported in literature and show a plethora of manifestations as described in the case report. They may not be apparent clinically, necessitating the use of imaging modalities and require careful evaluation to prevent complications. This paper presents a report of six double mesiodentes cases with negative family history for supernumerary teeth and absence of any syndromes. This is an effort to educate dentists about signs, symptoms, complications and management of mesiodentes. PMID:22678735

  5. Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

    Science.gov (United States)

    Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

    1984-12-01

    Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia.

  6. Hedging Double Barriers with Singles

    NARCIS (Netherlands)

    Sbuelz, A.

    2000-01-01

    Double barrier options provide risk managers with good-deal flexibility in tailoring portfolio returns.Their hedges offer full protection only if unwound along the barriers.This work provides non-dynamic hedges that project the risk of double barriers on to single barriers.Non-dynamic hedges overcom

  7. Properties of double field theory

    NARCIS (Netherlands)

    Penas, Victor Alejandro

    2016-01-01

    In this thesis we study several aspects of Double Field Theory (DFT). In general, Double Field Theory is subject to the so-called strong constraint. By using the Flux Formulation of DFT, we explore to what extent one can deal with the gauge consistency constraints of DFT without imposing the strong

  8. The Cambridge double star atlas

    CERN Document Server

    MacEvoy, Bruce; Mullaney, James; Tirion, Wil; Mullaney, James

    2015-01-01

    The Cambridge Double Star Atlas is back! It is the first and only atlas of physical double stars that can be viewed with amateur astronomical instruments. Completely rewritten, this new edition explains the latest research into double stars, and looks at the equipment, techniques and opportunities that will enable you to discover, observe and measure them. The target list has been completely revised and extended to 2500 binary or multiple systems. Each system is described with the most recent and accurate data from the authoritative Washington Double Star Catalog, including the HD and SAO numbers that are most useful in our digital age. Hundreds of remarks explain the attributes of local, rapidly changing, often measured or known orbital systems. The color atlas charts by Wil Tirion have been updated to help you easily find and identify the target systems, as well as other deep-sky objects. This is an essential reference for double star observers..

  9. Associations of IL-4, IL-6, and IL-12 levels in peripheral blood with lung function, cellular immune function, and quality of life in children with moderate-to-severe asthma

    Science.gov (United States)

    Cui, Ai-Hua; Zhao, Jing; Liu, Shu-Xiang; Hao, Ying-Shuang

    2017-01-01

    Abstract Background: Pediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma. Methods: A total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study. Enzyme-linked immunosorbent assay was used to detect IL-4, IL-6, and IL-12 levels. T lymphocytes were detected by alkaline phosphatase antialkaline phosphatase, and erythrocyte immune was measured by red blood cell C 3b receptor (RBC-C3bR) rosette-forming test. The forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were detected, after which FEV1/forced vital capacity (FVC) was calculated before and after treatment. PedsQL3.0 was used to measure the effect of asthma on QOL of children, and the correlation between IL-4, IL-6, and IL-12 levels and the lung function and QOL was measured. Logistic regression analysis was applied to detect related factors of moderate-to-severe asthma of children. Results: After treatment, the decreased IL-4 and IL-6 levels and increased IL-12 level were revealed in the experimental group. The cellular immune function's disorder was significantly decreased, and an elevated CD3, CD4, CD8, and declined CD4/CD8 level was performed in T lymphocytes. RBC-C3bR was increased, and red blood cell immune complex (RBC-IC) was reduced in erythrocyte immune in comparison with those before treatment. Lung function parameters all increased. After treatment, the symptoms of asthma in children reduced with scores of increased QOL. IL-4 was positively related to RBC-IC, but negatively associated with the QOL score. IL-6 showed negative connection with CD4/CD8, RBC-C3bR, FEV1/FVC, and QOL score, and had positive connection

  10. Associations of IL-4, IL-6, and IL-12 levels in peripheral blood with lung function, cellular immune function, and quality of life in children with moderate-to-severe asthma.

    Science.gov (United States)

    Cui, Ai-Hua; Zhao, Jing; Liu, Shu-Xiang; Hao, Ying-Shuang

    2017-03-01

    Pediatric asthma has gained increasing concerns with poorly understood pathogenesis. The purpose of this study was to explore the associations of interleukin-4 (IL-4), IL-6, and IL-12 levels in peripheral blood (PB) with lung function, cellular immune function, and children's quality of life (QOL) with moderate-to-severe asthma. A total of 1158 children with moderate-to-severe asthma (the experimental group) and 1075 healthy children (the control group) were recruited for our study. Enzyme-linked immunosorbent assay was used to detect IL-4, IL-6, and IL-12 levels. T lymphocytes were detected by alkaline phosphatase antialkaline phosphatase, and erythrocyte immune was measured by red blood cell C 3b receptor (RBC-C3bR) rosette-forming test. The forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were detected, after which FEV1/forced vital capacity (FVC) was calculated before and after treatment. PedsQL3.0 was used to measure the effect of asthma on QOL of children, and the correlation between IL-4, IL-6, and IL-12 levels and the lung function and QOL was measured. Logistic regression analysis was applied to detect related factors of moderate-to-severe asthma of children. After treatment, the decreased IL-4 and IL-6 levels and increased IL-12 level were revealed in the experimental group. The cellular immune function's disorder was significantly decreased, and an elevated CD3, CD4, CD8, and declined CD4/CD8 level was performed in T lymphocytes. RBC-C3bR was increased, and red blood cell immune complex (RBC-IC) was reduced in erythrocyte immune in comparison with those before treatment. Lung function parameters all increased. After treatment, the symptoms of asthma in children reduced with scores of increased QOL. IL-4 was positively related to RBC-IC, but negatively associated with the QOL score. IL-6 showed negative connection with CD4/CD8, RBC-C3bR, FEV1/FVC, and QOL score, and had positive connection with PEF. In addition, IL-12 was

  11. How quantum are non-negative wavefunctions?

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, M. B. [Station Q, Microsoft Research, Santa Barbara, California 93106-6105, USA and Quantum Architectures and Computation Group, Microsoft Research, Redmond, Washington 98052 (United States)

    2016-01-15

    We consider wavefunctions which are non-negative in some tensor product basis. We study what possible teleportation can occur in such wavefunctions, giving a complete answer in some cases (when one system is a qubit) and partial answers elsewhere. We use this to show that a one-dimensional wavefunction which is non-negative and has zero correlation length can be written in a “coherent Gibbs state” form, as explained later. We conjecture that such holds in higher dimensions. Additionally, some results are provided on possible teleportation in general wavefunctions, explaining how Schmidt coefficients before measurement limit the possible Schmidt coefficients after measurement, and on the absence of a “generalized area law” [D. Aharonov et al., in Proceedings of Foundations of Computer Science (FOCS) (IEEE, 2014), p. 246; e-print arXiv.org:1410.0951] even for Hamiltonians with no sign problem. One of the motivations for this work is an attempt to prove a conjecture about ground state wavefunctions which have an “intrinsic” sign problem that cannot be removed by any quantum circuit. We show a weaker version of this, showing that the sign problem is intrinsic for commuting Hamiltonians in the same phase as the double semion model under the technical assumption that TQO-2 holds [S. Bravyi et al., J. Math. Phys. 51, 093512 (2010)].

  12. Negative hydrogen ion production mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Bacal, M. [UPMC, LPP, Ecole Polytechnique, UMR CNRS 7648, Palaiseau (France); Wada, M. [School of Science and Engineering, Doshisha University, Kyoto 610-0321 (Japan)

    2015-06-15

    Negative hydrogen/deuterium ions can be formed by processes occurring in the plasma volume and on surfaces facing the plasma. The principal mechanisms leading to the formation of these negative ions are dissociative electron attachment to ro-vibrationally excited hydrogen/deuterium molecules when the reaction takes place in the plasma volume, and the direct electron transfer from the low work function metal surface to the hydrogen/deuterium atoms when formation occurs on the surface. The existing theoretical models and reported experimental results on these two mechanisms are summarized. Performance of the negative hydrogen/deuterium ion sources that emerged from studies of these mechanisms is reviewed. Contemporary negative ion sources do not have negative ion production electrodes of original surface type sources but are operated with caesium with their structures nearly identical to volume production type sources. Reasons for enhanced negative ion current due to caesium addition to these sources are discussed.

  13. Negative hydrogen ion production mechanisms

    Science.gov (United States)

    Bacal, M.; Wada, M.

    2015-06-01

    Negative hydrogen/deuterium ions can be formed by processes occurring in the plasma volume and on surfaces facing the plasma. The principal mechanisms leading to the formation of these negative ions are dissociative electron attachment to ro-vibrationally excited hydrogen/deuterium molecules when the reaction takes place in the plasma volume, and the direct electron transfer from the low work function metal surface to the hydrogen/deuterium atoms when formation occurs on the surface. The existing theoretical models and reported experimental results on these two mechanisms are summarized. Performance of the negative hydrogen/deuterium ion sources that emerged from studies of these mechanisms is reviewed. Contemporary negative ion sources do not have negative ion production electrodes of original surface type sources but are operated with caesium with their structures nearly identical to volume production type sources. Reasons for enhanced negative ion current due to caesium addition to these sources are discussed.

  14. Laser double Doppler flowmeter

    Science.gov (United States)

    Poffo, L.; Goujon, J.-M.; Le Page, R.; Lemaitre, J.; Guendouz, M.; Lorrain, N.; Bosc, D.

    2014-05-01

    The Laser Doppler flowmetry (LDF) is a non-invasive method for estimating the tissular blood flow and speed at a microscopic scale (microcirculation). It is used for medical research as well as for the diagnosis of diseases related to circulatory system tissues and organs including the issues of microvascular flow (perfusion). It is based on the Doppler effect, created by the interaction between the laser light and tissues. LDF measures the mean blood flow in a volume formed by the single laser beam, that penetrate into the skin. The size of this measurement volume is crucial and depends on skin absorption, and is not directly reachable. Therefore, current developments of the LDF are focused on the use of always more complex and sophisticated signal processing methods. On the other hand, laser Double Doppler Flowmeter (FL2D) proposes to use two laser beams to generate the measurement volume. This volume would be perfectly stable and localized at the intersection of the two laser beams. With FL2D we will be able to determine the absolute blood flow of a specific artery. One aimed application would be to help clinical physicians in health care units.

  15. Double Chooz: Latest results

    CERN Document Server

    Crespo-Anadón, J I

    2014-01-01

    The latest results from the Double Chooz experiment on the neutrino mixing angle $\\theta_{13}$ are presented. A detector located at an average distance of 1050 m from the two reactor cores of the Chooz nuclear power plant has accumulated a live time of 467.90 days, corresponding to an exposure of 66.5 GW-ton-year (reactor power $\\times$ detector mass $\\times$ live time). A revised analysis has boosted the signal efficiency and reduced the backgrounds and systematic uncertainties compared to previous publications, paving the way for the two detector phase. The measured $\\sin^2 2\\theta_{13} = 0.090^{+0.032}_{-0.029}$ is extracted from a fit to the energy spectrum. A deviation from the prediction above a visible energy of 4 MeV is found, being consistent with an unaccounted reactor flux effect, which does not affect the $\\theta_{13}$ result. A consistent value of $\\theta_{13}$ is measured in a rate-only fit to the number of observed candidates as a function of the reactor power, confirming the robustness of the ...

  16. Double acting bit holder

    Science.gov (United States)

    Morrell, Roger J.; Larson, David A.; Ruzzi, Peter L.

    1994-01-01

    A double acting bit holder that permits bits held in it to be resharpened during cutting action to increase energy efficiency by reducing the amount of small chips produced. The holder consist of: a stationary base portion capable of being fixed to a cutter head of an excavation machine and having an integral extension therefrom with a bore hole therethrough to accommodate a pin shaft; a movable portion coextensive with the base having a pin shaft integrally extending therefrom that is insertable in the bore hole of the base member to permit the moveable portion to rotate about the axis of the pin shaft; a recess in the movable portion of the holder to accommodate a shank of a bit; and a biased spring disposed in adjoining openings in the base and moveable portions of the holder to permit the moveable portion to pivot around the pin shaft during cutting action of a bit fixed in a turret to allow front, mid and back positions of the bit during cutting to lessen creation of small chip amounts and resharpen the bit during excavation use.

  17. Wages, Amenities and Negative Attitudes

    DEFF Research Database (Denmark)

    Waisman, Gisela; Larsen, Birthe

    We exploit the regional variation in negative attitudes towards immigrants to Sweden in order to analyse the consequences of the attitudes on immigrants welfare. We find that attitudes towards immigrants are of importance: they both affect their labour market outcomes and their quality of life. We...... interpret the negative effect on wages as evidence of labour market discrimination. We estimate the welfare effects of negative attitudes, through their wage and local amenities, for immigrants with different levels of skills, origin, gender and age....

  18. On Negation as Mitigation: The Case of Negative Irony

    Science.gov (United States)

    Giora, Rachel; Fein, Ofer; Ganzi, Jonathan; Levi, Natalie Alkeslassy; Sabah, Hadas

    2005-01-01

    Four experiments support the view of negation as mitigation (Giora, Balaban, Fein, & Alkabets, 2004). They show that when irony involves some sizable gap between what is said and what is criticized (He is exceptionally bright said of an idiot), it is rated as highly ironic (Giora, 1995). A negated version of that overstatement (He is not…

  19. Double-double electromagnetically induced transparency with amplification

    CERN Document Server

    Alotaibi, Hessa M M

    2013-01-01

    We show that an alkali atom with a tripod electronic structure can yield rich electromagnetically induced transparency phenomena even at room temperature. In particular we introduce double-double electromagnetically induced transparency wherein signal and probe fields each have two transparency windows. Their group velocities can be matched in either the first or second pair of transparency windows. Moreover signal and probe fields can each experience coherent gain in the second transparency windows. We explain using a semi-classical-dressed-picture to connect the tripod electronic structure to a double-\\Lambda\\ scheme.

  20. Causality, Nonlocality, and Negative Refraction.

    Science.gov (United States)

    Forcella, Davide; Prada, Claire; Carminati, Rémi

    2017-03-31

    The importance of spatial nonlocality in the description of negative refraction in electromagnetic materials has been put forward recently. We develop a theory of negative refraction in homogeneous and isotropic media, based on first principles, and that includes nonlocality in its full generality. The theory shows that both dissipation and spatial nonlocality are necessary conditions for the existence of negative refraction. It also provides a sufficient condition in materials with weak spatial nonlocality. These fundamental results should have broad implications in the theoretical and practical analyses of negative refraction of electromagnetic and other kinds of waves.

  1. Neurobiological background of negative symptoms.

    Science.gov (United States)

    Galderisi, Silvana; Merlotti, Eleonora; Mucci, Armida

    2015-10-01

    Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords "negative symptoms," "deficit schizophrenia," "persistent negative symptoms," "neurotransmissions," "neuroimaging" and "genetic." Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms.

  2. Income, Amenities and Negative Attitudes

    DEFF Research Database (Denmark)

    Waisman, Gisela; Larsen, Birthe

    2016-01-01

    ’ quality of life, they also affect their income. We estimate the utility effects of negative attitudes for refugees with different levels of education and gender. We also analyse how the size of the refugees’ networks relate to their quality of life and income as well as how negative attitudes towards......We exploit the regional variation in negative attitudes towards immigrants to Sweden in order to analyse the consequences of negative attitudes on refugees’ utility from labour income and amenities. We find that attitudes towards immigrants are important: while they affect mainly the refugees...

  3. Prestarlike functions with negative coefficients

    Directory of Open Access Journals (Sweden)

    H. Silverman

    1979-01-01

    Full Text Available The extreme points for prestarlike functions having negative coefficients are determined. Coefficient, distortion and radii of univalence, starlikeness, and convexity theorems are also obtained.

  4. Brain representations of negative numbers.

    Science.gov (United States)

    Parnes, Michael; Berger, Andrea; Tzelgov, Joseph

    2012-12-01

    Participants performed a physical comparison task of pairs of positive and pairs of negative one-digit numbers while their electrophysiological brain activity was measured. The numerical value of the presented digits was either congruent or incongruent with the physical size of the digits. Analysis has shown that the earliest event-related potential (ERP) difference between positive and negative numbers was found in the P300 ERP component peak, where there was an inverse effect of congruity in the negative pairs, compared with the positive ones. This pattern of results supports the idea that natural numbers serve as primitives of the human cognitive system, whereas negative numbers are apparently generated if needed.

  5. Neuroimaging correlates of negative priming.

    Science.gov (United States)

    Steel, C; Haworth, E J; Peters, E; Hemsley, D R; Sharma, T; Gray, J A; Pickering, A; Gregory, L; Simmons, A; Bullmore, E T; Williams, S C

    2001-11-16

    Many theoretical accounts of selective attention and memory retrieval include reference to active inhibitory processes, such as those argued to underlie the negative priming effect. fMRI was used in order to investigate the areas of cortical activation associated with Stroop interference, Stroop facilitation and Stroop negative priming tasks. The most significant activation within the negative priming task was within the inferior parietal lobule, left temporal lobe and frontal lobes. Areas of cortical activation are discussed with reference to theoretical accounts of the negative priming effect.

  6. 马克思对黑格尔辩证法结构的“双重否定”--阿尔都塞的马克思哲学史“认识论断裂”说述评%Double Connotations of Marx's Negating the Structure of Hegel's Dialectics:Commentary of Althusser's Break Theory of the History of Marx's Philosophy

    Institute of Scientific and Technical Information of China (English)

    冯务中; 郭玮

    2013-01-01

    阿尔都塞认为,马克思哲学史存在着“认识论断裂”问题。此见解的实质是:在理论实践和政治实践中,马克思对黑格尔辩证法结构具有“双重否定”。在理论实践方面,阿尔都塞对马克思所说的科学研究起点问题作了新解,却误读了马克思的本意。在政治实践方面,他以“结构”凸显了社会关系在历史唯物主义中的基础性,却忽略了“现实的个人”的地位。阿尔都塞的“断裂”说有其偏颇之处,但对人们重新理解马克思的本真精神富有启发意义。%Althusser holds that there is a “break” in Marx's Philosophy .The essence of this viewpoint is Marx's ne-gating the structure of Hegel's dialectics .The view of “negating” lies in theoretical and political practice .Althusser reinterprets the starting point of Marx's scientific research in theoretical practice , but he misreads Marx's original ide-a.And he attaches importance to structure to highlight the fundamentality of social relations in Marxism in political practice, but the importance of “actual individual” is ignored.Although Althusser's break theory is extreme , it pro-vides an illuminating insight into Marx's mind to us.

  7. Relevance research of viral load and peripheral T lymphocyte subset in patients with HIV and HBV coinfection%HIV、HBV共感染患者病毒载量和外周T淋巴细胞亚群的相关性研究

    Institute of Scientific and Technical Information of China (English)

    郑立娜; 金明珠

    2015-01-01

    Objective To investigate the correlation between viral load and peripheral T lymphocyte subset in patients with HIV and HBV coinfection. Methods From January 2011 to January 2014 in Yueqing Blood Supply Center of Out-patient and Inpatient Department, 1230 cases of untreated HIV infected patients with highly active antiretroviral thera-py were selected as simple infection group, 148 patients with HIV and HBV coinfection were selected as coinfection group. RT-PCR, fluorescent quantitative PCR and flow cytometry were adopted to detect the HIV and HBC viral load and T lymphocyte subsets count. Fully automatic biochemical analyzer was adopted to detect related biochemical index. The detection results between two groups were compared. The correlations between viral load and T lymphocyte subsets count in HIV and HBV coinfection patients were analyzed. Results ALT, AST, TP, ALB, TBIL level and HIV RNA load between two groups was compared respectively, there were significantly statistical differences (P< 0.01). CD4+, CD8+, CD3+T lymphocyte subsets count and CD4+/CD8+was compared respectively, there were significantly statistical differences (P<0.01).There was a positive correlation of HIV RNA load and HBV DNA load in coinfection patients (r=0.471). CD4+/CD8+was negatively correlate with HBV DNA load (r=-0.412). CD4+, CD4+/CD8+were negatively corre-late with HIV RNA load (r =-0.841,-0.583). Conclusion HBV may has promoting HIV RNA replication effect which makes a worse liver damage and immune system damage in coinfection patients than HIV infection along patients, should pay attention to in clinic.%目的:研究HIV、HBV共感染患者病毒载量与外周T淋巴细胞亚群的相关性。方法选取2011年1月~2014年1月就诊于乐清市血站门诊和住院部未经高效抗逆转录病毒治疗的HIV感染患者1230例为单纯感染组和HIV、HBV共感染患者148例为共感染组。采用RT-PCR、荧光定量PCR和流式细胞仪进行HIV、HBV病毒载量和T

  8. Progress in biological function of Api6/AIM/Spα in immune regulation and lipid metabolism%Api6/AIM/Spα调节免疫和脂质代谢的生物学功能研究

    Institute of Scientific and Technical Information of China (English)

    方严; 刘丹; 练雪梅

    2011-01-01

    Apoptosis inhibitor 6(Api6), also known as AIM and Spα, belongs to the scavenger receptor cysteine rich-superfamily (SRCR-SF). Api6/AIM/Spα, which is secreted exclusively by macrophages, inhibits apoptosis of CD4/CD8 double-positive (CD4+/CD8+) thymocytes, T cells, natural killer T(NKT) cells and macrophags. As a pattern recognition receptor, Api6/AIM/Spα is involved in the recognition of pathogen-associated molecular patterns(e.g. LPS and LTA), which suggests that it plays an important role in the regulation of the innate and adaptive immune systems. It has been confirmed recently that Api6/AIM/Spα increases early atherosclerotic lesion development by decreasing macrophage apoptosis. Api6/AIM/Spα also associates with cytosolic fatty acid synthase (FAS), decreases FAS activity, thereby inducing the lipolytic response within adipocytes and is physiologically relevanting to obesity progression. This paper introduced emphatically the progress in biological function of Api6/ AIM/Spα in immune regulation and lipid metabolism.%凋亡抑制因子6(apoptosis inhibitor 6,Api6),又称作AIM/Spa,是清道夫受体富含半胱氨酸残基超家族新成员.Api6/AIM/Spa由巨噬细胞特异性表达,具有抑制CD4+/CD8+双阳性胸腺细胞、T淋巴细胞、NKT淋巴细胞和巨噬细胞凋亡的作用.作为模式识别受体,Api6/AIM/Spα直接与病原体相关分子模式LPS/LTA结合,在机体固有免疫和适应性免疫中发挥重要的作用.近年研究发现,Api6/AIM/Spα可以通过抑制动脉粥样硬化斑块部位巨噬细胞凋亡加重动脉粥样硬化早期斑块的进展,也可以通过抑制脂肪酸合成酶(FAS)的生物学活性提高脂肪细胞的脂解作用,在肥胖的进展中发挥重要作用.重点综述了Api6/AIM/Spα调节免疫和脂质代谢等生物学功能的研究进展.

  9. Be Aware of Negative Reinforcement.

    Science.gov (United States)

    Cipani, Ennio C.

    1995-01-01

    This article examines the concept of negative reinforcement in relation to the maintenance of off-task and disruptive behaviors in classrooms. Suggestions are given for determining whether negative reinforcement (in the form of escape from the instructional task) or teacher attention is maintaining the behavior. Suggestions for making tasks less…

  10. Negative supervisionsoplevelser og deres konsekvenser

    DEFF Research Database (Denmark)

    Nielsen, Jan

    2011-01-01

    in evaluation. First part of the paper explores negative experience in supervision in general. The second part, focusing on negative experience in supervision caused by evaluation, is explored and discussed in relation to the key concept of supervisory alliance (Bordin, 1983), perceiving evaluation...

  11. Negative phototropism of rice root

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@It is often believed that the stem of higher plants has characteristics of positive phototropism, and the root shows no phototropism or no sensitivity to light though the root of Arabdopsis was reported possessing characteristics of negative phototropism. In this study, a distinct negative phototropism of the root system of rice seedlings was observed.

  12. Negative refraction in outer space?

    OpenAIRE

    Mackay, Tom G.; Lakhtakia, Akhlesh

    2004-01-01

    Mediums which do not support the propagation of plane waves with negative phase velocity (NPV) when viewed at rest can support NPV propagation when they are viewed in a reference frame which is uniformly translated at sufficiently high velocity. Thus, relativistic negative refraction may be exploited in astronomical scenarios.

  13. Aspects of the Doubled Worldsheet

    CERN Document Server

    Driezen, Sibylle; Thompson, Daniel C

    2016-01-01

    We clarify the relation between various approaches to the manifestly T-duality symmetric string. We explain in detail how the PST covariant doubled string arises from an unusual gauge fixing. We pay careful attention to the role of "spectator" fields in this process and also show how the T-duality invariant doubled dilaton emerges naturally. We extend these ideas to non-Abelian T-duality and show they give rise to the duality invariant formalism based on the semi-Abelian Drinfeld Double. We then develop the N=(0,1) supersymmetric duality invariant formalism.

  14. Don't Double Up on Acetaminophen

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Don't Double Up on Acetaminophen Share Tweet Linkedin Pin ... consumer organizations. AAC’s outreach campaign, "Double Check, Don't Double Up," is all about the safe use ...

  15. Physics of negative absolute temperatures

    Science.gov (United States)

    Abraham, Eitan; Penrose, Oliver

    2017-01-01

    Negative absolute temperatures were introduced into experimental physics by Purcell and Pound, who successfully applied this concept to nuclear spins; nevertheless, the concept has proved controversial: a recent article aroused considerable interest by its claim, based on a classical entropy formula (the "volume entropy") due to Gibbs, that negative temperatures violated basic principles of statistical thermodynamics. Here we give a thermodynamic analysis that confirms the negative-temperature interpretation of the Purcell-Pound experiments. We also examine the principal arguments that have been advanced against the negative temperature concept; we find that these arguments are not logically compelling, and moreover that the underlying "volume" entropy formula leads to predictions inconsistent with existing experimental results on nuclear spins. We conclude that, despite the counterarguments, negative absolute temperatures make good theoretical sense and did occur in the experiments designed to produce them.

  16. Negative Attitudes, Network and Education

    DEFF Research Database (Denmark)

    Bennett, Patrick; la Cour, Lisbeth; Larsen, Birthe

    to an ambiguous impact. Empirically, we consider immigrants’ high school attendance. On the macro-level, we confirm a signficant negative correlation between negative attitudes towards immigrants and high school attendance and a positive impact of networking on high school attendance. On the individual level, we...... use Danish register data to find a signficant positive correlation between negative attitudes towards immigrants and high school attendance and find a positive impact of networking on high school attendance. In both the macro and the micro-econometric analysis we run the same regressions for natives......We consider the impact of negative attitudes against immigrants and immigration on educational choice in a search and wage bargaining model including networking. We consider two cases in terms of the importance of negative attitudes againts immigrants for high and low educated individuals and find...

  17. Analysis of Negative Correlation Learning

    Institute of Scientific and Technical Information of China (English)

    Liu Yong; Zou Xiu-fen

    2003-01-01

    This paper describes negative correlation learning for designing neural network ensembles. Negative correlation learning has been firstly analysed in terms of minimising mutual information on a regression task. By ninimising the mutual information between variables extracted by two neural networks, they are forced to convey different information about some features of their input. Based on the decision boundaries and correct response sets, negative correlation learning has been further studied on two pattern classification problems. The purpose of examining the decision boundaries and the correct response sets is not only to illustrate the learning behavior of negative correlation learning, but also to cast light on how to design more effective neural network ensembles. The experimental results showed the decision boundary of the trained neural network ensemble by negative correlation learning is almost as good as the optimum decision boundary.

  18. Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Hvass, Henriette Cordes; Riber, Ulla; Jensen, Tim Kåre

    2012-01-01

    not boosted by the re-inoculation, since identical intestinal IgA responses developed in response to the inoculation in both the susceptible CC pigs and the protected RE pigs. A memory recall cell-mediated immune response developed in RE pigs which was significantly stronger compared to the primary response...... responses are likely mediators of protective immunity against L. intracellularis, with CD8+ effector cells and CD4+CD8+ double positive memory T cells as main contributors to the antigen-specific IFN-γ production.......To investigate immune responses upon re-infection with Lawsonia intracellularis, local and peripheral humoral and cell-mediated immune responses to primary and challenge inoculations were studied in 22 pigs. Pigs were orally inoculated with virulent L. intracellularis at the age of 5-6 weeks...

  19. A review of the human vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Jungersen, Gregers;

    2015-01-01

    predictive non-rodent model is needed for the study of genital chlamydia in women. The pig has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human female genital tract and associated immune system...... in cycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show similar cyclic changes. The immune system in pigs is very similar to that of humans, even though pigs have a higher percentage of CD4(+)/CD8(+) double positive T cells. The genital immune system......Sexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a good...

  20. Why double-stranded RNA resists condensation

    Energy Technology Data Exchange (ETDEWEB)

    Tolokh, Igor S.; Pabit, Suzette; Katz, Andrea M.; Chen, Yujie; Drozdetski, Aleksander; Baker, Nathan A.; Pollack, Lois; Onufriev, Alexey

    2014-09-15

    The addition of small amounts of multivalent cations to solutions containing double-stranded DNA leads to attraction between the negatively charged helices and eventually to condensation. Surprisingly, this effect is suppressed in double-stranded RNA, which carries the same charge as the DNA, but assumes a different double helical form. However, additional characterization of short (25 base-pairs) nucleic acid (NA) duplex structures by circular dichroism shows that measured differences in condensation are not solely determined by duplex helical geometry. Here we combine experiment, theory, and atomistic simulations to propose a mechanism that connects the observed variations in condensation of short NA duplexes with the spatial variation of cobalt hexammine (CoHex) binding at the NA duplex surface. The atomistic picture that emerged showed that CoHex distributions around the NA reveals two major NA-CoHex binding modes -- internal and external -- distinguished by the proximity of bound CoHex to the helical axis. Decreasing trends in experimentally observed condensation propensity of the four studied NA duplexes (from B-like form of homopolymeric DNA, to mixed sequence DNA, to DNA:RNA hybrid, to A-like RNA) are explained by the progressive decrease of a single quantity: the fraction of CoHex ions in the external binding mode. Thus, while NA condensation depends on a complex interplay between various structural and sequence features, our coupled experimental and theoretical results suggest a new model in which a single parameter connects the NA condensation propensity with geometry and sequence dependence of CoHex binding.