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Sample records for local antigen-specific suppression

  1. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

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    Kleinhenz, M.E.; Ellner, J.J.

    1985-07-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the (/sup 3/H)thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced (/sup 3/H)thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% (SD)) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition.

  2. Immunoregulatory adherent cells in human tuberculosis: radiation-sensitive antigen-specific suppression by monocytes

    International Nuclear Information System (INIS)

    Kleinhenz, M.E.; Ellner, J.J.

    1985-01-01

    In human tuberculosis, adherent mononuclear cells (AMC) selectively depress in vitro responses to the mycobacterial antigen tuberculin purified protein derivative (PPD). The phenotype of this antigen-specific adherent suppressor cell was characterized by examining the functional activity of adherent cells after selective depletion of sheep erythrocyte-rosetting T cells or OKM1-reactive monocytes. Adherent cell suppression was studied in the [ 3 H]thymidine-incorporation microculture assay by using T cells rigorously depleted of T cells with surface receptors for the Fc portion of IgG (T gamma cells) as antigen-responsive cells. PPD-induced [ 3 H]thymidine incorporation by these non gamma T cells was uniformly reduced (mean, 42% +/- 10% [SD]) when autologous AMC were added to non gamma T cells at a ratio of 1:2. Antigen-specific suppression by AMC was not altered by depletion of sheep erythrocyte-rosetting T cells or treatment with indomethacin. However, AMC treated with OKM1 and complement or gamma irradiation (1,500 rads) no longer suppressed tuberculin responses in vitro. These studies identify the antigen-specific adherent suppressor cell in tuberculosis as an OKM1-reactive, non-erythrocyte-rosetting monocyte. The radiosensitivity of this monocyte immunoregulatory function may facilitate its further definition

  3. Zinc supplementation induces CD4+CD25+Foxp3+ antigen-specific regulatory T cells and suppresses IFN-γ production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1.

    Science.gov (United States)

    Maywald, Martina; Rink, Lothar

    2017-08-01

    The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. Cell proliferation and pro-inflammatory cytokine production were monitored by [ 3 H]-thymidine proliferation assay and ELISA, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and mRNA analysis were used for Foxp3, KLF-10, and IRF-1 expression. Zinc supplementation on antigen-specific T cells in physiological doses (50 µM) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on MLC results in an increased induction and stabilization of CD4 + CD25 + Foxp3 + and CD4 + CD25 + CTLA-4 + T cells (p zinc-induced upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. However, in resting lymphocytes zinc increases IRF-1. In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets: Foxp3, KLF-10, and IRF-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions.

  4. Tolerogenic dendritic cells from poorly compensated type 1 diabetes patients have decreased ability to induce stable antigen-specific T cell hyporesponsiveness and generation of suppressive regulatory T cells

    DEFF Research Database (Denmark)

    Dánova, Klara; Grohova, Anna; Strnadova, Pavla

    2017-01-01

    state of patients. tolDCs differentiated from both groups of patients acquired a regulatory phenotype and an anti-inflammatory profile. Interestingly, tolDCs from well-controlled patients expressed higher levels of inhibitory molecules IL-T3 and PD-L1. Additionally, glutamic acid decarboxylase (GAD)65......Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing b cells leading to hyperglycemia that, in turn, specifically...... suppressive abilities. The functionality of tolDCs was confirmed in the adoptive transfer model of NOD-SCID mice where tolDCs delayed diabetes onset. These results suggest that metabolic control of T1D affects the functional characteristics of tolDCs and subsequent effector T cell responses. Metabolic control...

  5. Screening Immunomodulators To Skew the Antigen-Specific Autoimmune Response.

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    Northrup, Laura; Sullivan, Bradley P; Hartwell, Brittany L; Garza, Aaron; Berkland, Cory

    2017-01-03

    Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.

  6. Antigenic specificity of serum antibodies in mice fed soy protein

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Bruun, S.W.; Frøkiær, Hanne

    2003-01-01

    Background: Soybean protein is used in a number of food products but unfortunately is also a common cause of food allergy. Upon ingestion of soy protein, healthy mice like other animals and humans generate a soy-specific antibody response in the absence of signs of illness. Not much is known about...... the relationship between the immunogenic proteins involved in this nondeleterious antibody response and the pathological response associated with food allergy. The objective of the present study was to characterize the antigenic specificity of the soy protein-specific antibody response generated in healthy mice...... ingesting soy protein. Methods: Blood from mice fed a soy-containing diet was analyzed using ELISA and immunoblot for antibody reactivity towards various soy protein fractions and pure soy proteins/subunits. Mice bred on a soy-free diet were used as controls. Results: The detectable antigenic specificity...

  7. Dissection of T-cell antigen specificity in human melanoma

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Albæk Thrue, Charlotte; Junker, Niels

    2012-01-01

    Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma-as...... from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined....

  8. Human Tregs Made Antigen Specific by Gene Modification: The Power to Treat Autoimmunity and Antidrug Antibodies with Precision

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    Patrick R. Adair

    2017-09-01

    Full Text Available Human regulatory CD4+ T cells (Tregs are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII. Seminal clinical trials have used polyclonal Tregs, but the frequency of antigen-specific Tregs among polyclonal populations is low, and polyclonal Tregs may risk non-specific immunosuppression. Antigen-specific Treg therapy, which uses genetically modified Tregs expressing receptors specific for target antigens, greatly mitigates this risk. Building on the principles of T-cell receptor cloning, chimeric antigen receptors (CARs, and a novel CAR derivative, called B-cell antibody receptors, our lab has developed different types of antigen-specific Tregs. This review discusses the current research and optimization of gene-modified antigen-specific human Tregs in our lab in several disease models. The preparations and considerations for clinical use of such Tregs also are discussed.

  9. Use of a solid-phase radioimmunoassay and formalin-fixed whole bacterial antigen in the detection of antigen-specific immunoglobulin in prostatic fluid.

    OpenAIRE

    Shortliffe, L M; Wehner, N; Stamey, T A

    1981-01-01

    The prostatic fluid of two patients with Escherichia coli bacterial prostatitis was analyzed for evidence of a local immune response to bacterial infection. A solid-phase radioimmunoassay was modified to measure the immunoglobulin (Ig)A and IgG antigen-specific antibody responses to infecting bacteria in serum and prostatic fluid from patient. Formalin-fixed whole E. coli were used as antigen. In one patient with acute E. coli prostatic infection, measurements of antigen-specific antibody con...

  10. Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System

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    Raul Vizcardo

    2018-03-01

    Full Text Available Summary: Induced pluripotent stem cell (iPSC-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs. iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies. : A barrier for clinical application of iPSC-derived CD8 T cells using OP9/DLL1 is their abnormal biology. Vizcardo et al. show that a 3D thymic culture system enables the generation of a homogeneous antigen-specific T cell subset, named iTEs, which closely mimics naive T cells and exhibits potent anti-tumor activity. Keywords: thymopoiesis, T cell differentiation, iPSC differentiation, adoptive cell transfer, naïve T cell, recent rhymic emigrants, fetal thymus organ culture, immunotherapy, 3D culture, tumor antigen specific T cell

  11. Characterization of a human antigen specific helper factor

    International Nuclear Information System (INIS)

    Richardson, B.

    1986-01-01

    While antigen (Ag) specific helper factors have been characterized in mice, similar molecules have not been identified in humans. To characterize human antigen specific helper molecules, an IL-2 dependent tetanus toxoid (T.T.) reactive T cell line was fused with a 6-thioguanine resistant CEM line, and hybrids selected in medium containing hypoxanthine and azaserine. Hybrids were screened by culturing the cells with 35 S-Met then reacting the supernatants with T.T. or hepatitis vaccine immobilized on nitrocellulose. One hybrid, TT6BA-O, was identified which secreted a Met-containing molecule which bound T.T. but not hepatitis vaccine. Supernatants from TT6BA-O, but not the parent CEM line, when added to autologous peripheral blood mononuclear cells (PBMC's) stimulated secretion of T.T. specific antibodies (Abs). Specificity controls demonstrated that TT6BA-O supernatant did not induce antibodies to diphtheria toxoid, hepatitis vaccine or pneumococcal polysaccharide, and total immunoglobulin (lg) synthesis was minimally increased. In contrast, pokeweed mitogen stimulated significant lg synthesis as well as Ab's to pneumococcal polysaccharide and T.T. TT6BA-O supernatant induced anti-T.T.Ab's in autologous PBMC's but not PBMC's from 3 unrelated donors, suggesting that the activity of the helper factor is restricted, possibly by the MHC. The molecular weight of the helper factor was estimated at 100,000-150,000 by Sephacryl S-300 chromatography. Finally, the helper factor could be demonstrated to bind and elute from sephorose-immobilized T.T. and anti-DR antisera, but not anti-lg antisera or the T40/25 monoclonal antibody, which binds a nonpolymorphic determinant on the human T cell receptor. These results demonstrate that human Ag specific helper factors exist, bind antigen and bear class II MHC determinants

  12. Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus.

    Science.gov (United States)

    Cerullo, V; McCormack, W; Seiler, M; Mane, V; Cela, R; Clarke, C; Rodgers, J R; Lee, B

    2007-12-01

    As efficient and less toxic virus-derived gene therapy vectors are developed, a pressing problem is to avoid immune response to the therapeutic gene product. Secreted therapeutic proteins potentially represent a special problem, as they are readily available to professional antigen-presenting cells throughout the body. Some studies suggest that immunity to serum proteins can be avoided in some mouse strains by using tissue-specific promoters. Here we show that expression of human alpha1-antitrypsin (AAT) was nonimmunogenic in the immune-responsive strain C3H/HeJ, when expressed from helper-dependent (HD) vectors using ubiquitous as well as tissue-specific promoters. Coadministration of less immunogenic HD vectors with an immunogenic first-generation vector failed to immunize, suggesting immune suppression rather than immune stealth. Indeed, mice primed with HD vectors were tolerant to immune challenge with hAAT emulsified in complete Freund's adjuvant. Such animals developed high-titer antibodies to coemulsified human serum albumin, showing that tolerance was antigen specific. AAT-specific T cell responses were depressed in tolerized animals, suggesting that tolerance affects both T and B cells. These results are consistent with models of high-dose tolerance of B cells and certain other suppressive mechanisms, and suggest that a high level of expression from HD vectors can be sufficient to induce specific immune tolerance to serum proteins.

  13. Pretreatment antigen-specific immunity and regulation - association with subsequent immune response to anti-tumor DNA vaccination.

    Science.gov (United States)

    Johnson, Laura E; Olson, Brian M; McNeel, Douglas G

    2017-07-18

    Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics. In the current study, we sought to determine if measures of antigen-specific or antigen non-specific immunity were present prior to treatment, and associated with subsequent immune response, to identify possible predictive immune biomarkers. Patients who developed persistent PAP-specific, IFNγ-secreting immune responses were defined as immune "responders." The frequency of peripheral T cell and B cell lymphocytes, natural killer cells, monocytes, dendritic cells, myeloid derived suppressor cells, and regulatory T cells were assessed by flow cytometry and clinical laboratory values. PAP-specific immune responses were evaluated by cytokine secretion in vitro, and by antigen-specific suppression of delayed-type hypersensitivity to a recall antigen in an in vivo SCID mouse model. The frequency of peripheral blood cell types did not differ between the immune responder and non-responder groups. Non-responder patients tended to have higher PAP-specific IL-10 production pre-vaccination (p = 0.09). Responder patients had greater preexisting PAP-specific bystander regulatory responses that suppressed DTH to a recall antigen (p = 0.016). While our study population was small (n = 38), these results suggest that different measures of antigen-specific tolerance or regulation might help predict immunological outcome from DNA vaccination. These will be prospectively evaluated in an ongoing randomized, phase II trial.

  14. A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro.

    Directory of Open Access Journals (Sweden)

    Tatsuya Moutai

    Full Text Available Immunotherapies such as adoptive transfer of T cells or natural killer cells, or monoclonal antibody (MoAb treatment have recently been recognized as effective means to treat cancer patients. However, adoptive transfer of B cells or plasma cells producing tumor-specific antibodies has not been applied as a therapy because long-term culture and selective expansion of antigen-specific B cells has been technically very difficult. Here, we describe a novel cancer immunotherapy that uses B-cell adoptive transfer. We demonstrate that germinal-center-like B cells (iGB cells induced in vitro from mouse naïve B cells become plasma cells and produce IgG antibodies for more than a month in the bone marrow of non-irradiated recipient mice. When transferred into mice, iGB cells producing antibody against a surrogate tumor antigen suppressed lung metastasis and growth of mouse melanoma cells expressing the same antigen and prolonged survival of the recipients. In addition, we have developed a novel culture system called FAIS to selectively expand antigen-specific iGB cells utilizing the fact that iGB cells are sensitive to Fas-induced cell death unless their antigen receptors are ligated by membrane-bound antigens. The selected iGB cells efficiently suppressed lung metastasis of melanoma cells in the adoptive immunotherapy model. As human blood B cells can be propagated as iGB cells using culture conditions similar to the mouse iGB cell cultures, our data suggest that it will be possible to treat cancer-bearing patients by the adoptive transfer of cancer-antigen-specific iGB cells selected in vitro. This new adoptive immunotherapy should be an alternative to the laborious development of MoAb drugs against cancers for which no effective treatments currently exist.

  15. Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3

    NARCIS (Netherlands)

    Spits, H.; Yssel, H.; Leeuwenberg, J.; de Vries, J. E.

    1985-01-01

    T3 is a human differentiation antigen expressed exclusively on mature T cells. In this study it is shown that anti-T3 monoclonal antibodies, in addition to their capacity to induce T cells to proliferate, are able to induce antigen-specific cytotoxic T lymphocyte clones to mediate antigen

  16. T Lymphocyte-Endothelial Interactions: Emerging Understanding of Trafficking and Antigen-Specific Immunity

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    Christopher Vincent Carman

    2015-11-01

    Full Text Available Antigen-specific immunity requires regulated trafficking of T cells in and out of diverse tissues in order to orchestrate lymphocyte development, immune surveillance, responses and memory. The endothelium serves as a unique barrier, as well as a sentinel, between the blood and the tissues and as such it plays an essential locally tuned role in regulating T cell migration and information exchange. While it is well established that chemoattractants and adhesion molecules are major determinants of T cell trafficking, emerging studies have now enumerated a large number of molecular players as well as a range of discrete cellular remodeling activities (e.g. transmigratory cups and invadosome-like protrusions, IPLs that participate in directed migration and pathfinding by T cells. In addition to providing trafficking cues, intimate cell-cell interaction between lymphocytes and endothelial cells provide instruction to T cells that influence their activation and differentiation states. Perhaps the most intriguing and underappreciated of these ‘sentinel’ roles is the ability of the endothelium to act as a non-hematopoietic ‘semi-professional’ antigen-presenting cell. Close contacts between circulating T cells and antigen-presenting endothelium may play unique non-redundant roles in shaping adaptive immune responses within the periphery. A better understanding of the mechanisms directing T cell trafficking and the antigen-presenting role of the endothelium may not only increase our knowledge of the adaptive immune response but also empower the utility of emerging immunomodulatory therapeutics.

  17. SPATIAL DISTRIBUTIONS OF ABSORPTION, LOCAL SUPPRESSION, AND EMISSIVITY REDUCTION OF SOLAR ACOUSTIC WAVES IN MAGNETIC REGIONS

    International Nuclear Information System (INIS)

    Chou, D.-Y.; Yang, M.-H.; Zhao Hui; Liang Zhichao; Sun, M.-T.

    2009-01-01

    Observed acoustic power in magnetic regions is lower than the quiet Sun because of absorption, emissivity reduction, and local suppression of solar acoustic waves in magnetic regions. In the previous studies, we have developed a method to measure the coefficients of absorption, emissivity reduction, and local suppression of sunspots. In this study, we go one step further to measure the spatial distributions of three coefficients in two active regions, NOAA 9055 and 9057. The maps of absorption, emissivity reduction, and local suppression coefficients correlate with the magnetic map, including plage regions, except the emissivity reduction coefficient of NOAA 9055 where the emissivity reduction coefficient is too weak and lost among the noise.

  18. NOG-hIL-4-Tg, a new humanized mouse model for producing tumor antigen-specific IgG antibody by peptide vaccination.

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    Yoshie Kametani

    Full Text Available Immunodeficient mice transplanted with human peripheral blood mononuclear cells (PBMCs are promising tools to evaluate human immune responses to vaccines. However, these mice usually develop severe graft-versus-host disease (GVHD, which makes estimation of antigen-specific IgG production after antigen immunization difficult. To evaluate antigen-specific IgG responses in PBMC-transplanted immunodeficient mice, we developed a novel NOD/Shi-scid-IL2rγnull (NOG mouse strain that systemically expresses the human IL-4 gene (NOG-hIL-4-Tg. After human PBMC transplantation, GVHD symptoms were significantly suppressed in NOG-hIL-4-Tg compared to conventional NOG mice. In kinetic analyses of human leukocytes, long-term engraftment of human T cells has been observed in peripheral blood of NOG-hIL-4-Tg, followed by dominant CD4+ T rather than CD8+ T cell proliferation. Furthermore, these CD4+ T cells shifted to type 2 helper (Th2 cells, resulting in long-term suppression of GVHD. Most of the human B cells detected in the transplanted mice had a plasmablast phenotype. Vaccination with HER2 multiple antigen peptide (CH401MAP or keyhole limpet hemocyanin (KLH successfully induced antigen-specific IgG production in PBMC-transplanted NOG-hIL-4-Tg. The HLA haplotype of donor PBMCs might not be relevant to the antibody secretion ability after immunization. These results suggest that the human PBMC-transplanted NOG-hIL-4-Tg mouse is an effective tool to evaluate the production of antigen-specific IgG antibodies.

  19. Rapid desensitization induces internalization of antigen-specific IgE on mouse mast cells.

    Science.gov (United States)

    Oka, Tatsuya; Rios, Eon J; Tsai, Mindy; Kalesnikoff, Janet; Galli, Stephen J

    2013-10-01

    Rapid desensitization transiently prevents severe allergic reactions, allowing administration of life-saving therapies in previously sensitized patients. However, the mechanisms underlying successful rapid desensitization are not fully understood. We sought to investigate whether the mast cell (MC) is an important target of rapid desensitization in mice sensitized to exhibit IgE-dependent passive systemic anaphylaxis in vivo and to investigate the antigen specificity and underlying mechanisms of rapid desensitization in our mouse model. C57BL/6 mice (in vivo) or primary isolated C57BL/6 mouse peritoneal mast cells (PMCs; in vitro) were passively sensitized with antigen-specific anti-2,4-dinitrophenyl IgE, anti-ovalbumin IgE, or both. MCs were exposed over a short period of time to increasing amounts of antigen (2,4-dinitrophenyl-human serum albumin or ovalbumin) in the presence of extracellular calcium in vitro or by means of intravenous administration to sensitized mice in vivo before challenging the mice with or exposing the PMCs to optimal amounts of specific or irrelevant antigen. Rapidly exposing mice or PMCs to progressively increasing amounts of specific antigen inhibited the development of antigen-induced hypothermia in sensitized mice in vivo and inhibited antigen-induced PMC degranulation and prostaglandin D2 synthesis in vitro. Such MC hyporesponsiveness was induced antigen-specifically and was associated with a significant reduction in antigen-specific IgE levels on MC surfaces. Rapidly exposing MCs to progressively increasing amounts of antigen can both enhance the internalization of antigen-specific IgE on the MC surface and also desensitize these cells in an antigen-specific manner in vivo and in vitro. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  20. Detection of Avian Antigen-Specific T Cells Induced by Viral Vaccines

    DEFF Research Database (Denmark)

    Dalgaard, Tina Sørensen; Norup, Liselotte Rothmann; Juul-Madsen, Helle Risdahl

    2016-01-01

    Live attenuated viral vaccines are widely used in commercial poultry production, but the development of new effective inactivated/subunit vaccines is needed. Studies of avian antigen-specific T cells are primarily based on analyses ex vivo after activating the cells with recall antigen. There is ......Live attenuated viral vaccines are widely used in commercial poultry production, but the development of new effective inactivated/subunit vaccines is needed. Studies of avian antigen-specific T cells are primarily based on analyses ex vivo after activating the cells with recall antigen...

  1. Lumped Mass Modeling for Local-Mode-Suppressed Element Connectivity

    DEFF Research Database (Denmark)

    Joung, Young Soo; Yoon, Gil Ho; Kim, Yoon Young

    2005-01-01

    connectivity parameterization (ECP) is employed. On the way to the ultimate crashworthy structure optimization, we are now developing a local mode-free topology optimization formulation that can be implemented in the ECP method. In fact, the local mode-freeing strategy developed here can be also used directly...... experiencing large structural changes, appears to be still poor. In ECP, the nodes of the domain-discretizing elements are connected by zero-length one-dimensional elastic links having varying stiffness. For computational efficiency, every elastic link is now assumed to have two lumped masses at its ends....... Choosing appropriate penalization functions for lumped mass and link stiffness is important for local mode-free results. However, unless the objective and constraint functions are carefully selected, it is difficult to obtain clear black-and-white results. It is shown that the present formulation is also...

  2. Antigen-specific tolerance inhibits autoimmune uveitis in pre-sensitized animals by deletion and CD4+CD25+ T-regulatory cells.

    Science.gov (United States)

    Matta, Bharati; Jha, Purushottam; Bora, Puran S; Bora, Nalini S

    2010-02-01

    The objective of this study was to inhibit experimental autoimmune anterior uveitis (EAAU) by establishing antigen-specific immune tolerance in animals pre-sensitized with melanin-associated antigen (MAA). Intravenous administration of MAA on days 6, 7, 8 and 9 post-immunization induced tolerance and inhibited EAAU in all Lewis rats. The number of cells (total T cells, CD4(+) T cells and CD8(+) T cells) undergoing apoptosis dramatically increased in the popliteal lymph nodes (LNs) of the tolerized animals compared with non-tolerized animals. In addition, Fas ligand (FasL), TNF receptor 1 (TNFR1) and caspase-8 were upregulated in tolerized rats. Proliferation of total lymphocytes, CD4(+)T cells and CD8(+) T cells (harvested from the popliteal LNs) in response to antigenic stimulation was drastically reduced in the state of tolerance compared with the cells from non-tolerized animals. The level of interferon (IFN)-gamma and IL-2 decreased, whereas TGF-beta2 was elevated in the state of tolerance. Furthermore, the number of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) increased in the popliteal LNs of tolerized animals compared with non-tolerized animals. In conclusion, our results suggest that deletion of antigen-specific T cells by apoptosis and active suppression mediated by Tregs has an important role in the induction of antigen specific immune tolerance in animals with an established immune response against MAA.

  3. Anomalously suppressed localization in the two-channel Anderson model

    International Nuclear Information System (INIS)

    Nguyen, Ba Phi; Kim, Kihong

    2012-01-01

    We study numerically the localization properties of a two-channel quasi-one-dimensional Anderson model with uncorrelated diagonal disorder within the nearest-neighbor tight-binding approximation. We calculate and analyze the disorder-averaged transmittance and the Lyapunov exponent. We find that the localization of the entire system is enhanced by increasing the interchain hopping strength t-tilde. From the numerical investigation of the energy dependence of the Lyapunov exponent for many different interchain hopping strengths, we find that apart from the band center anomaly, which usually occurs in strictly one-dimensional disordered systems, additional anomalies appear at special spectral points. They are found to be associated with the interchain hopping strength and occur at E=± t-tilde/2 and ± t-tilde. We find that the anomalies at E=± t-tilde are associated with the π-coupling occurring within one energy band and those at E=± t-tilde/2 are associated with the π-coupling occurring between two different energy bands. Despite having a similar origin, these two anomalies have distinct characteristics in their dependence on the strength of disorder. We also show that for a suitable range of parameter values, effectively delocalized states are observed in finite-size systems. (paper)

  4. Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

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    Shigeo Koido

    2010-01-01

    Full Text Available The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs that can reduce the tumor mass. Dendritic cells (DCs are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.

  5. Visualization of antigen-specific human cytotoxic T lymphocytes labeled with superparamagnetic iron-oxide particles

    Energy Technology Data Exchange (ETDEWEB)

    Beer, Ambros J. [Technical University of Munich (TUM), Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Holzapfel, Konstantin; Settles, Marcus; Rummeny, Ernst J. [Technical University of Munich, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Neudorfer, Juliana; Kroenig, Holger; Peschel, Christian; Bernhard, Helga [TUM, Munich, Department of Hematology/Oncology, Klinikum rechts der Isar, Munich (Germany); Piontek, Guido; Schlegel, Juergen [TUM, Munich, Division of Neuropathology, Institute of Pathology, Klinikum rechts der Isar, Munich (Germany)

    2008-06-15

    New technologies are needed to characterize the migration and survival of antigen-specific T cells in vivo. In this study, we developed a novel technique for the labeling of human cytotoxic T lymphocytes with superparamagnetic iron-oxide particles and the subsequent depiction with a conventional 1.5-T magnetic resonance scanner. Antigen-specific CD8{sup +} T lymphocytes were labeled with ferucarbotran by lipofection. The uptake of ferucarbotran was confirmed by immunofluorescence microscopy using a dextran-specific antibody, and the intracellular enrichment of iron was measured by atomic absorption spectrometry. The imaging of T cells was performed by magnetic resonance on day 0, 2, 7 and 14 after the labeling procedure. On day 0 and 2 post labeling, a pronounced shortening of T2*-relaxation times was observed, which diminished after 7 days and was not detectable anymore after 14 days, probably due to the retained mitotic activity of the labeled T cells. Of importance, the antigen-specific cytolytic activity of the T cells was preserved following ferucarbotran labeling. Efficient ferucarbotran labeling of functionally active T lymphocytes and their detection by magnetic resonance imaging allows the in vivo monitoring of T cells and, subsequently, will impact the further development of T cell-based therapies. (orig.)

  6. Visualization of antigen-specific human cytotoxic T lymphocytes labeled with superparamagnetic iron-oxide particles

    International Nuclear Information System (INIS)

    Beer, Ambros J.; Holzapfel, Konstantin; Settles, Marcus; Rummeny, Ernst J.; Neudorfer, Juliana; Kroenig, Holger; Peschel, Christian; Bernhard, Helga; Piontek, Guido; Schlegel, Juergen

    2008-01-01

    New technologies are needed to characterize the migration and survival of antigen-specific T cells in vivo. In this study, we developed a novel technique for the labeling of human cytotoxic T lymphocytes with superparamagnetic iron-oxide particles and the subsequent depiction with a conventional 1.5-T magnetic resonance scanner. Antigen-specific CD8 + T lymphocytes were labeled with ferucarbotran by lipofection. The uptake of ferucarbotran was confirmed by immunofluorescence microscopy using a dextran-specific antibody, and the intracellular enrichment of iron was measured by atomic absorption spectrometry. The imaging of T cells was performed by magnetic resonance on day 0, 2, 7 and 14 after the labeling procedure. On day 0 and 2 post labeling, a pronounced shortening of T2*-relaxation times was observed, which diminished after 7 days and was not detectable anymore after 14 days, probably due to the retained mitotic activity of the labeled T cells. Of importance, the antigen-specific cytolytic activity of the T cells was preserved following ferucarbotran labeling. Efficient ferucarbotran labeling of functionally active T lymphocytes and their detection by magnetic resonance imaging allows the in vivo monitoring of T cells and, subsequently, will impact the further development of T cell-based therapies. (orig.)

  7. Analysis of antigen-specific B-cell memory directly ex vivo.

    Science.gov (United States)

    McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

    2004-01-01

    Helper T-cell-regulated B-cell memory develops in response to initial antigen priming as a cellular product of the germinal center (GC) reaction. On antigen recall, memory response precursors expand rapidly with exaggerated differentiation into plasma cells to produce the high-titer, high-affinity antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a high-resolution flow cytometric strategy to quantify the emergence and maintenance of antigen-specific memory B cells directly ex vivo. Extended cell surface phenotype establishes a level of cellular diversity not previously appreciated for the memory B-cell compartment. Using an "exclusion transfer" strategy, we ascertain the capacity of two distinct memory B-cell populations to transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence expressed messenger ribonucleic acid (mRNA) from single cells within the population to estimate the level of somatic hypermutation as the best molecular indicator of B-cell memory. In this chapter, we describe the methods used in each of these four sections that serve to provide high-resolution quantification of antigen-specific B-cell memory responses directly ex vivo.

  8. Rapid production of antigen-specific monoclonal antibodies from a variety of animals

    Directory of Open Access Journals (Sweden)

    Kurosawa Nobuyuki

    2012-09-01

    Full Text Available Abstract Background Although a variety of animals have been used to produce polyclonal antibodies against antigens, the production of antigen-specific monoclonal antibodies from animals remains challenging. Results We propose a simple and rapid strategy to produce monoclonal antibodies from a variety of animals. By staining lymph node cells with an antibody against immunoglobulin and a fluorescent dye specific for the endoplasmic reticulum, plasma/plasmablast cells were identified without using a series of antibodies against lineage markers. By using a fluorescently labeled antigen as a tag for a complementary cell surface immunoglobulin, antigen-specific plasma/plasmablast cells were sorted from the rest of the cell population by fluorescence-activated cell sorting. Amplification of cognate pairs of immunoglobulin heavy and light chain genes followed by DNA transfection into 293FT cells resulted in the highly efficient production of antigen-specific monoclonal antibodies from a variety of immunized animals. Conclusions Our technology eliminates the need for both cell propagation and screening processes, offering a significant advantage over hybridoma and display strategies.

  9. Developing antigen-specific therapies in multiple sclerosis: a tale of Tantalus or Ulysses?

    Science.gov (United States)

    van Noort JM

    1999-10-01

    Autoreactive T-cell responses directed to myelin proteins in the central nervous system are widely believed to be crucial in the pathology of multiple sclerosis (MS). However, effective ways of selectively targeting these T-cells in order to alter the clinical course of MS in a predictable manner has yet to be demonstrated. This review discusses two recent developments of crucial importance to the rational development of antigen-specific therapy in MS. The very idea of antigen-specific therapy in MS has long faced the challenge of determinant spreading, i.e., the development of novel autoimmune responses as the consequence of tissue damage. This phenomenon has led many to expect that in ongoing MS, many different pathogenic specificities would accumulate. Obviously, this would render antigen-specific therapy very difficult. Recent data now suggest that determinant spreading is most likely to be a transient phenomenon limited only to the first stages of tissue damage. A second development has changed our perspective on the specificity of individual T-cells and, thus, on the suitability of various ways to implement antigen-specific therapy. Evidence is rapidly accumulating that T-cell receptors are much more cross-reactive than previously assumed. This notion poses unexpected challenges to therapeutic approaches in MS that are based on selective targeting of autoreactive TCR. Vaccination with TCR peptides, administration of anti-TCR antibodies and development of therapeutically altered peptide ligands all depend on a significant level of predictability of pathogenic TCR. With such predictability now turning out to be much lower than was previously hoped, selective TCR-directed strategies for intervention may therefore turn out to be much less effective than anticipated. In the development of antigen-specific therapies, the use of whole protein tolerogens now seems to be the most promising route. Oral, intranasal or iv. administration of antigen remain viable options

  10. Requirements on localized current drive for the suppression of neoclassical tearing modes

    NARCIS (Netherlands)

    Bertelli, N.; De Lazzari, D.; Westerhof, E.

    2011-01-01

    A heuristic criterion for the full suppression of an NTM was formulated as eta(NTM) = j(CD,max)/j(BS) >= 1.2 (Zohm et al 2005 J. Phys. Conf. Ser. 25 234), where j(CD,max) is the maximum in the driven current density profile applied to stabilize the mode and j(BS) is the local bootstrap current

  11. Radiotherapy and local hyperthermia plus androgen suppression in locally advanced prostate cancer

    International Nuclear Information System (INIS)

    Maluta, S.; Marciai, N.; Gabbani, M.; Palazzi, M.; Dall'Oglio, S.; Grandinetti, A.

    2005-01-01

    Full text: In advanced prostatic cancer, hyperthermia may be useful in order to enhance irradiation efficacy so to avoid delivering of too high dose of radiotherapy which increases acute and late sequelae. A multi-centric phase II study is warranted to give hyperthermia a level 3 evidence in prostate cancer treatment. A randomized phase III study to demonstrate efficacy of hyperthermia is not available because of the optimal results obtained by using radiotherapy combined with androgen suppression. To evaluate hyperthermia gain, LHT should be combined with radiotherapy alone in patients refusing androgen suppression or affected by hormone refractory prostate carcinoma (HRPC). Patients with HRPC have multiple possibilities of treatment improving performance status and median survival, as chemotherapy regimens, and new agents. All these treatments modalities need to be confirmed by phase III trials. Also hyperthermia may be considered among these promising approaches. (author)

  12. Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

    Directory of Open Access Journals (Sweden)

    Karasuyama Hajime

    2011-04-01

    Full Text Available Abstract Background There have been few reports on the role of Fc receptors (FcRs and immunoglobulin G (IgG in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa. Methods In FcγRIIB deficient (KO and C57BL/6 (WT mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA. Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL. Results In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously. Conclusion Antigen-specific IgG ameliorates

  13. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells.

    Science.gov (United States)

    Correa, Isabel; Ilieva, Kristina M; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F; Tutt, Andrew N J; Nestle, Frank O; Karagiannis, Panagiotis; Lacy, Katie E; Karagiannis, Sophia N

    2018-01-01

    Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

  14. Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

    Science.gov (United States)

    Gunasekaran, Manojkumar; Chatterjee, Prodyot K.; Shih, Andrew; Imperato, Gavin H.; Addorisio, Meghan; Kumar, Gopal; Lee, Annette; Graf, John F.; Meyer, Dan; Marino, Michael; Puleo, Christopher; Ashe, Jeffrey; Cox, Maureen A.; Mak, Tak W.; Bouton, Chad; Sherry, Barbara; Diamond, Betty; Andersson, Ulf; Coleman, Thomas R.; Metz, Christine N.; Tracey, Kevin J.; Chavan, Sangeeta S.

    2018-01-01

    The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses. PMID:29755449

  15. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

    Directory of Open Access Journals (Sweden)

    Isabel Correa

    2018-03-01

    Full Text Available Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1 specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires.

  16. Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

    Directory of Open Access Journals (Sweden)

    Manojkumar Gunasekaran

    2018-04-01

    Full Text Available The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR, dorsal root ganglion (DRG sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM into wild-type (WT mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

  17. Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells

    Science.gov (United States)

    Correa, Isabel; Ilieva, Kristina M.; Crescioli, Silvia; Lombardi, Sara; Figini, Mariangela; Cheung, Anthony; Spicer, James F.; Tutt, Andrew N. J.; Nestle, Frank O.; Karagiannis, Panagiotis; Lacy, Katie E.; Karagiannis, Sophia N.

    2018-01-01

    Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires. PMID:29628923

  18. Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

    Science.gov (United States)

    Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

    2015-05-01

    Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

  19. Identification of antigen-specific human monoclonal antibodies using high-throughput sequencing of the antibody repertoire.

    Science.gov (United States)

    Liu, Ju; Li, Ruihua; Liu, Kun; Li, Liangliang; Zai, Xiaodong; Chi, Xiangyang; Fu, Ling; Xu, Junjie; Chen, Wei

    2016-04-22

    High-throughput sequencing of the antibody repertoire provides a large number of antibody variable region sequences that can be used to generate human monoclonal antibodies. However, current screening methods for identifying antigen-specific antibodies are inefficient. In the present study, we developed an antibody clone screening strategy based on clone dynamics and relative frequency, and used it to identify antigen-specific human monoclonal antibodies. Enzyme-linked immunosorbent assay showed that at least 52% of putative positive immunoglobulin heavy chains composed antigen-specific antibodies. Combining information on dynamics and relative frequency improved identification of positive clones and elimination of negative clones. and increase the credibility of putative positive clones. Therefore the screening strategy could simplify the subsequent experimental screening and may facilitate the generation of antigen-specific antibodies. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Allopurinol reduces antigen-specific and polyclonal activation of human T cells

    Directory of Open Access Journals (Sweden)

    Damián ePérez-Mazliah

    2012-09-01

    Full Text Available Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases.

  1. MEASUREMENTS OF ABSORPTION, EMISSIVITY REDUCTION, AND LOCAL SUPPRESSION OF SOLAR ACOUSTIC WAVES IN SUNSPOTS

    International Nuclear Information System (INIS)

    Chou, D.-Y.; Liang, Z.-C.; Yang, M.-H.; Zhao Hui; Sun, M.-T.

    2009-01-01

    The power of solar acoustic waves in magnetic regions is lower relative to the quiet Sun. Absorption, emissivity reduction, and local suppression of acoustic waves contribute to the observed power reduction in magnetic regions. We propose a model for the energy budget of acoustic waves propagating through a sunspot in terms of the coefficients of absorption, emissivity reduction, and local suppression of the sunspot. Using the property that the waves emitted along the wave path between two points have no correlation with the signal at the starting point, we can separate the effects of these three mechanisms. Applying this method to helioseismic data filtered with direction and phase-velocity filters, we measure the fraction of the contribution of each mechanism to the power deficit in the umbra of the leading sunspot of NOAA 9057. The contribution from absorption is 23.3 ± 1.3%, emissivity reduction 8.2 ± 1.4%, and local suppression 68.5 ± 1.5%, for a wave packet corresponding to a phase velocity of 6.98 x 10 -5 rad s -1 .

  2. Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice

    International Nuclear Information System (INIS)

    Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.; Simpson, T.J.

    1986-01-01

    Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells

  3. Object Localization Does Not Imply Awareness of Object Category at the Break of Continuous Flash Suppression

    Directory of Open Access Journals (Sweden)

    Florian Kobylka

    2017-06-01

    Full Text Available In continuous flash suppression (CFS, a dynamic noise masker, presented to one eye, suppresses conscious perception of a test stimulus, presented to the other eye, until the suppressed stimulus comes to awareness after few seconds. But what do we see breaking the dominance of the masker in the transition period? We addressed this question with a dual-task in which observers indicated (i whether the test object was left or right of the fixation mark (localization and (ii whether it was a face or a house (categorization. As done recently Stein et al. (2011a, we used two experimental varieties to rule out confounds with decisional strategy. In the terminated mode, stimulus and masker were presented for distinct durations, and the observers were asked to give both judgments at the end of the trial. In the self-paced mode, presentation lasted until the observers responded. In the self-paced mode, b-CFS durations for object categorization were about half a second longer than for object localization. In the terminated mode, correct categorization rates were consistently lower than correct detection rates, measured at five duration intervals ranging up to 2 s. In both experiments we observed an upright face advantage compared to inverted faces and houses, as concurrently reported in b-CFS studies. Our findings reveal that more time is necessary to enable observers judging the nature of the object, compared to judging that there is “something other” than the noise which can be localized, but not recognized. This suggests gradual transitions in the first break of CFS. Further, the results imply that suppression is such that no cues to object identity are conveyed in potential “leaks” of CFS (Gelbard-Sagiv et al., 2016.

  4. Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

    Science.gov (United States)

    Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp

    2012-04-01

    Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Total and antigen-specific Ige levels in umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Sybilski AJ

    2009-12-01

    Full Text Available Abstract The present study was conducted to learn whether the perinatal and environmental factors could influence the total and antigen-specific IgE levels in umbilical cord blood. Retrospective data were obtained from 173 mother-infant pairs. Total and specific (for children's food, wheat/grass and house dust mite-HDM cord blood IgE levels were determined using the immunoassay test. The total cord blood IgE was between 0.0-23.08 IU/ml (mean 0.55 ± 2.07 IU/ml; median 0.16 IU/ml. Total IgE levels were significantly higher in boys compared with girls (OR = 2.2; P = 0.007, and in newborns with complicated pregnancy (OR = 2.7; P = 0.003. A greater number of siblings correlated with increases in the total cord blood IgE (P

  6. Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine

    Directory of Open Access Journals (Sweden)

    Li B

    2016-11-01

    Full Text Available Bo Li,1,2 Michael Siuta,1 Vanessa Bright,1,2 Dmitry Koktysh,3,4 Brittany K Matlock,5 Megan E Dumas,1 Meiying Zhu,1 Alex Holt,1 Donald Stec,3,6 Shenglou Deng,7 Paul B Savage,7 Sebastian Joyce,8,9 Wellington Pham1,2,6,10–12 1Institute of Imaging Science, Vanderbilt University School of Medicine, 2Department of Radiology and Radiological Sciences, 3Department of Chemistry, Vanderbilt University, 4Vanderbilt Institute of Nanoscale Science and Engineering, 5Vanderbilt Flow Cytometry Shared Resource, Vanderbilt University, 6Vanderbilt Institute of Chemical Biology, 7Department of Chemistry and Biochemistry, Brigham Young University, 8Department of Pathology, Microbiology and Immunology, Vanderbilt University, 9Veterans Administration Tennessee Valley Healthcare System, 10Department of Biomedical Engineering, 11Vanderbilt Ingram Cancer Center, 12Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA Abstract: The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova and an adjuvant within the poly(lactic-co-glycolic acid nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days. The in vivo immunization studies exhibited that the nanovaccine induced stronger and longer immune responses compared to its soluble counterpart. Similarly, intranasal inhalation of the nanovaccine induced more robust antigen-specific CD8+ T cell response than intraperitoneal injection of nanovaccine

  7. Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization.

    Science.gov (United States)

    Reyes, L; Hartikka, J; Bozoukova, V; Sukhu, L; Nishioka, W; Singh, G; Ferrari, M; Enas, J; Wheeler, C J; Manthorpe, M; Wloch, M K

    2001-06-14

    Antigen specific immune responses were characterized after intramuscular immunization of BALB/c mice with 5 antigen encoding plasmid DNAs (pDNAs) complexed with Vaxfectin, a cationic lipid formulation. Vaxfectin increased IgG titers for all of the antigens with no effect on the CTL responses to the 2 antigens for which CTL assays were performed. Both antigen specific IgG1 and IgG2a were increased, although IgG2a remained greater than IgG1. Furthermore, Vaxfectin had no effect on IFN-gamma or IL-4 production by splenocytes re-stimulated with antigen, suggesting that the Th1 type responses typical of intramuscular pDNA immunization were not altered. Studies with IL-6 -/- mice suggest that the antibody enhancement is IL-6 dependent and results in a correlative increase in antigen specific antibody secreting cells.

  8. Local Turbulence Suppression and Shear Flow Dynamics During qmin-Triggered Internal Transport Barriers on DIII-D

    Science.gov (United States)

    Shafer, M. W.; McKee, G. R.; Schlossberg, D. J.; Austin, M. E.; Burrell, K. H.

    2008-11-01

    Long-wavelength turbulence (kρiITBs) may form. Application of off-axis ECH slows the q-profile evolution and increases ρqmin, both of which enhance turbulence measurements using a new high-sensitivity large-area (8x,8) 2D BES array. The measured transient turbulence suppression is localized to the low-order rational surface (qmin= 2, 5/2, 3, etc.). Measured poloidal flow shear transiently exceeds the turbulence decorrelation rate, which is consistent with shear suppression. The localized suppression zone propagates radially outward, nearly coincident with the low-order surface.

  9. IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity.

    Science.gov (United States)

    Tran, Giang T; Hodgkinson, Suzanne J; Carter, Nicole M; Verma, Nirupama D; Plain, Karren M; Boyd, Rochelle; Robinson, Catherine M; Nomura, Masaru; Killingsworth, Murray; Hall, Bruce M

    2012-05-10

    Immune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

  10. Single-dilution enzyme-linked immunosorbent assay for quantification of antigen-specific salmonid antibody

    Science.gov (United States)

    Alcorn, S.W.; Pascho, R.J.

    2000-01-01

    An enzyme-linked immunosorbent assay (ELISA) was developed on the basis of testing a single dilution of serum to quantify the level of antibody to the p57 protein of Renibaclerium salmoninarum in sockeye salmon (Oncorhynchus nerka). The levels of antibody were interpolated from a standard curve constructed by relating the optical densities (OD) produced by several dilutions of a high-titer rainbow trout (O. mykiss) antiserum to the p57 protein. The ELISA OD values produced by as many as 36 test sera on each microplate were compared with the standard curve to calculate the antigen-specific antibody activity. Repeated measurements of 36 samples on 3 microplates on each of 6 assay dates indicated that the mean intraassay coefficient of variation (CV) was 6.68% (range, 0-23%) and the mean interassay CV was 8.29% (range, 4-16%). The antibody levels determined for the serum sample from 24 sockeye salmon vaccinated with a recombinant p57 protein generally were correlated with the levels determined by endpoint titration (r2 = 0.936) and with results from another ELISA that was based on extrapolation of antibody levels from a standard curve (r2 = 0.956). The single-dilution antibody ELISA described here increases the number of samples that can be tested on each microplate compared with immunoassays based on analysis of several dilutions of each test serum. It includes controls for interassay standardization and can be used to test fish weighing <3 g.

  11. Characterization of Antigen-Specific B Cells Using Nominal Antigen-Coated Flow-Beads

    Science.gov (United States)

    Akl, Ahmed; Lepetit, Maud; Crochette, Romain; Giral, Magali; Lepourry, Julie; Pallier, Annaick; Castagnet, Stéphanie; Dugast, Emilie; Guillot-Gueguen, Cécile; Jacq-Foucher, Marylène; Saulquin, Xavier; Cesbron, Anne; Laplaud, David; Nicot, Arnaud; Brouard, Sophie; Soulillou, Jean-Paul

    2013-01-01

    In order to characterize the reactivity of B cells against nominal antigens, a method based on the coupling of antigens onto the surface of fluorescent core polystyrene beads was developed. We first demonstrate that murine B cells with a human MOG-specific BCR are able to interact with MOG-coated beads and do not recognize beads coated with human albumin or pp65. B cells purified from human healthy volunteer blood or immunized individuals were tested for their ability to interact with various nominal antigens, including viral, vaccine, self and alloantigens, chosen for their usefulness in studying a variety of pathological processes. A substantial amount of B cells binding self-antigen MOG-coated beads can be detected in normal blood. Furthermore, greater frequencies of B cell against anti-Tetanic Toxin or anti-EBNA1 were observed in primed individuals. This method can reveal increased frequencies of anti-HLA committed B cells in patients with circulating anti-HLA antibodies compared to unsensitized patients and normal individuals. Of interest, those specific CD19 cells were preferentially identified within CD27−IgD+ (i-e naïve) subset. These observations suggest that a broad range of medical situations could benefit from a tool that allows the detection, the quantification and the characterization of antigen-specific blood B cells. PMID:24386360

  12. Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine

    International Nuclear Information System (INIS)

    Yoshikawa, Tomoaki; Imazu, Susumu; Gao Jianqing; Hayashi, Kazuyuki; Tsuda, Yasuhiro; Shimokawa, Mariko; Sugita, Toshiki; Niwa, Takako; Oda, Atushi; Akashi, Mitsuru; Tsutsumi, Yasuo; Mayumi, Tadanori; Nakagawa, Shinsaku

    2004-01-01

    In an attempt to enhance the immunological efficacy of genetic immunization, we investigated a new biological means for delivering antigen gene directly to the cytoplasm via membrane fusion. In this context, we investigated fusogenic liposome (FL) encapsulating DNA as a possible genetic immunization vehicle. RT-PCR analysis indicated that a FL could introduce and express encapsulating OVA gene efficiently and rapidly in vitro. Consistent with this observation, an in vitro assay showed that FL-mediated antigen-gene delivery can induce potent presentation of antigen via the MHC class I-dependent pathway. Accordingly, immunization with FL containing the OVA-gene induced potent OVA-specific Th1 and Th2 cytokine production. Additionally, OVA-specific CTL responses and antibody production were also observed in systemic compartments including the spleen, upon immunization with the OVA-gene encapsulating FL. These findings suggest that FL is an effective genetic immunization carrier system for the stimulation of antigen-specific immune responses against its encoding antigen

  13. Development of an epitope panel for consistent identification of antigen-specific T-cells in humans

    DEFF Research Database (Denmark)

    Fløe, Andreas; Løppke, Caroline; Hilberg, Ole

    2017-01-01

    Objective We aimed to establish a panel of MHC-peptide multimers suitable as a positive control in detection of HLA A*0201 restricted antigen specific T-cells (ASTC) by flow cytometry. Materials and methods MHC Dextramers were loaded with HLA A*0201 binding peptides from viral antigens and melano...

  14. Manipulating the Lewis antigen specificity of the cholesterol-dependent cytolysin lectinolysin

    Directory of Open Access Journals (Sweden)

    Sara eLawrence

    2012-11-01

    Full Text Available The cholesterol-dependent cytolysins (CDCs attack cells by punching large holes in their membranes. Lectinolysin from Streptococcus mitis is unique among CDCs due to the presence of an N-terminal lectin domain that enhances the pore-forming activity of the toxin. We recently determined the crystal structures of the lectin domain in complex with various glycans. These structures revealed the molecular basis for the Lewis antigen specificity of the toxin. Based on this information we have used in silico molecular modelling to design a mutant toxin, which we predicted would increase its specificity for Lewis y, an antigen found on the surface of cancer cells. Surprisingly, we found by surface plasmon resonance binding experiments that the resultant mutant lectin domain exhibited higher specificity for Lewis b antigens instead. We then undertook comparative crystallographic and molecular dynamics simulation studies of the wild-type and mutant lectin domains to understand the molecular basis for the disparity between the theoretical and experimental results. The crystallographic results revealed that the net number of interactions between Lewis y and wild-type versus mutant was unchanged whereas there was a loss of a hydrogen bond between mutant and Lewis b compared to wild-type. In contrast, the molecular dynamics studies revealed that the Lewis b antigen spent more time in the binding pocket of the mutant compared to wild-type and the reverse was true for Lewis y. The results of these simulation studies are consistent with the conclusions drawn from the surface plasmon resonance studies. This work is part of a program to engineer lectinolysin so that it will target and kill specific cells in human diseases.

  15. MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Edward G., E-mail: edward_walsh@brown.edu [Brown University, Department of Neuroscience (United States); Mills, David R. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Lim, Sierin; Sana, Barindra [Nanyang Technological University, Division of Bioengineering (Singapore); Brilliant, Kate E. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Park, William K. C. [Rhode Island Hospital, Department of Diagnostic Imaging (United States)

    2013-01-15

    A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r{sub 1} and r{sub 2}. The r{sub 1} and r{sub 2} values of the uniformly distributed modified ferritin were significantly higher (r{sub 1} = 1,290 mM{sup -1} s{sup -1} and r{sub 2} = 5,740 mM{sup -1} s{sup -1}) than values observed for wild-type ferritin (e.g., horse spleen, r{sub 1} = 0.674 mM{sup -1} s{sup -1}, r{sub 2} = 95.54 mM{sup -1} s{sup -1}). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T{sub 2} contrast with negligible T{sub 1} effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

  16. Suppressing Klein tunneling in graphene using a one-dimensional array of localized scatterers.

    Science.gov (United States)

    Walls, Jamie D; Hadad, Daniel

    2015-02-13

    Graphene's unique physical and chemical properties make it an attractive platform for use in micro- and nanoelectronic devices. However, electrostatically controlling the flow of electrons in graphene can be challenging as a result of Klein tunneling, where electrons normally incident to a one-dimensional potential barrier of height V are perfectly transmitted even as V → ∞. In this study, theoretical and numerical calculations predict that the transmission probability for an electron wave normally incident to a one-dimensional array of localized scatterers can be significantly less than unity when the electron wavelength is smaller than the spacing between scatterers. In effect, placing periodic openings throughout a potential barrier can, somewhat counterintuitively, decrease transmission in graphene. Our results suggest that electrostatic potentials with spatial variations on the order of the electron wavelength can suppress Klein tunneling and could find applications in developing graphene electronic devices.

  17. Random noise suppression of seismic data using non-local Bayes algorithm

    Science.gov (United States)

    Chang, De-Kuan; Yang, Wu-Yang; Wang, Yi-Hui; Yang, Qing; Wei, Xin-Jian; Feng, Xiao-Ying

    2018-02-01

    For random noise suppression of seismic data, we present a non-local Bayes (NL-Bayes) filtering algorithm. The NL-Bayes algorithm uses the Gaussian model instead of the weighted average of all similar patches in the NL-means algorithm to reduce the fuzzy of structural details, thereby improving the denoising performance. In the denoising process of seismic data, the size and the number of patches in the Gaussian model are adaptively calculated according to the standard deviation of noise. The NL-Bayes algorithm requires two iterations to complete seismic data denoising, but the second iteration makes use of denoised seismic data from the first iteration to calculate the better mean and covariance of the patch Gaussian model for improving the similarity of patches and achieving the purpose of denoising. Tests with synthetic and real data sets demonstrate that the NL-Bayes algorithm can effectively improve the SNR and preserve the fidelity of seismic data.

  18. Suppression of local invasion of ameloblastoma by inhibition of matrix metalloproteinase-2 in vitro

    International Nuclear Information System (INIS)

    Wang, Anxun; Zhang, Bin; Huang, Hongzhang; Zhang, Leitao; Zeng, Donglin; Tao, Qian; Wang, Jianguang; Pan, Chaobin

    2008-01-01

    Ameloblastomas are odontogenic neoplasms characterized by local invasiveness. This study was conducted to address the role of matrix metalloproteinase-2 (MMP-2) in the invasiveness of ameloblastomas. Plasmids containing either MMP-2 siRNA or tissue inhibitor of metalloproteinase-2 (TIMP-2) cDNA were created and subsequently transfected into primary ameloblastoma cells. Zymography, RT-PCR, and Western blots were used to assess MMP-2 activity and expression of MMP-2 and TIMP-2, as well as protein levels. Primary cultures of ameloblastoma cells expressed cytokeratin (CK) 14 and 16, and MMP-2, but only weakly expressed CK18 and vimentin. MMP-2 mRNA and protein levels were significantly inhibited by RNA interference (P < 0.05). Both MMP-2 siRNA and TIMP-2 overexpression inhibited MMP-2 activity and the in vitro invasiveness of ameloblastoma. These results indicate that inhibition of MMP-2 activity suppresses the local invasiveness of ameloblastoma cells. This mechanism may serve as a novel therapeutic target in ameloblastomas pursuant to additional research

  19. Affinity isolation of antigen-specific circulating B cells for generation of phage display-derived human monoclonal antibodies

    DEFF Research Database (Denmark)

    Ditzel, Henrik

    2009-01-01

    A method is described for affinity isolation of antigen-specific circulating B cells of interest for subsequent generation of immune antibody phage display libraries. This approach should overcome the problem of low yields of monoclonal antibodies of interest in the libraries generated from...... peripheral blood lymphocytes caused by the low abundance of antigen-specific B cells in the circulation. The preselection of B cells is based on the specificity of the surface Ig receptor and is accomplished using the antigen of interest conjugated to magnetic beads. This method should significantly increase...... the frequency of antibody phage particles of interest in the library and allow for efficient isolation monoclonal antibodies with the predefined specificity....

  20. Immunizations with hepatitis B viral antigens and a TLR7/8 agonist adjuvant induce antigen-specific immune responses in HBV-transgenic mice

    Directory of Open Access Journals (Sweden)

    Ying Wang

    2014-12-01

    Conclusions: Immunization with CL097-conjugated HBV-Ag reversed immune tolerance in HBV-Tg mice and induced antigen-specific immune responses. TLR7/8 agonists appear to be potent adjuvants for the induction of antigen-specific Th1 responses in an immune tolerant state.

  1. Induction of antigen-specific immunity by pH-sensitive carbonate apatite as a potent vaccine carrier

    International Nuclear Information System (INIS)

    Hebishima, Takehisa; Tada, Seiichi; Takeshima, Shin-nosuke; Akaike, Toshihiro; Ito, Yoshihiro; Aida, Yoko

    2011-01-01

    Highlights: ► To develop effective vaccine, we examined the effects of CO 3 Ap as an antigen carrier. ► OVA contained in CO 3 Ap was taken up by BMDCs more effectively than free OVA. ► OVA-immunized splenocytes was activated by OVA contained in CO 3 Ap effectively. ► OVA contained in CO 3 Ap induced strong OVA-specific immune responses to C57BL/6 mice. ► CO 3 Ap is promising antigen carrier for the achievement of effective vaccine. -- Abstract: The ability of carbonate apatite (CO 3 Ap) to enhance antigen-specific immunity was examined in vitro and in vivo to investigate its utility as a vaccine carrier. Murine bone marrow-derived dendritic cells took up ovalbumin (OVA) containing CO 3 Ap more effectively than free OVA. Interestingly, mice immunized with OVA-containing CO 3 Ap produced OVA-specific antibodies more effectively than mice immunized with free OVA. Furthermore, immunization of C57BL/6 mice with OVA-containing CO 3 Ap induced the proliferation and antigen-specific production of IFN-γ by splenocytes more strongly than immunization with free OVA. Moreover, no significant differences were detected in the induction of delayed-type hypersensitivity responses, an immune reaction involving an antigen-specific, cell-mediated immune response between OVA-containing CO 3 Ap and OVA-containing alumina salt (Alum), suggesting that CO 3 Ap induced cell-mediated immune response to the same degree as Alum, which is commonly used for clinical applications. This study is the first to demonstrate the induction of antigen-specific immune responses in vivo by CO 3 Ap.

  2. Kinetics of antigen specific and non-specific polyclonal B-cell responses during lethal Plasmodium yoelii malaria

    Directory of Open Access Journals (Sweden)

    Laurence Rolland

    1992-06-01

    Full Text Available In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B-cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17 XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weigth ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection,in parallel to the parasitemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin-containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium-derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin-secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen-induced stimulation of antigen-specific cells rather than a generalized non-specific (mitogen-induced triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation.

  3. Isolation and characterization of antigen-specific alpaca (Lama pacos) VHH antibodies by biopanning followed by high-throughput sequencing.

    Science.gov (United States)

    Miyazaki, Nobuo; Kiyose, Norihiko; Akazawa, Yoko; Takashima, Mizuki; Hagihara, Yosihisa; Inoue, Naokazu; Matsuda, Tomonari; Ogawa, Ryu; Inoue, Seiya; Ito, Yuji

    2015-09-01

    The antigen-binding domain of camelid dimeric heavy chain antibodies, known as VHH or Nanobody, has much potential in pharmaceutical and industrial applications. To establish the isolation process of antigen-specific VHH, a VHH phage library was constructed with a diversity of 8.4 × 10(7) from cDNA of peripheral blood mononuclear cells of an alpaca (Lama pacos) immunized with a fragment of IZUMO1 (IZUMO1PFF) as a model antigen. By conventional biopanning, 13 antigen-specific VHHs were isolated. The amino acid sequences of these VHHs, designated as N-group VHHs, were very similar to each other (>93% identity). To find more diverse antibodies, we performed high-throughput sequencing (HTS) of VHH genes. By comparing the frequencies of each sequence between before and after biopanning, we found the sequences whose frequencies were increased by biopanning. The top 100 sequences of them were supplied for phylogenic tree analysis. In total 75% of them belonged to N-group VHHs, but the other were phylogenically apart from N-group VHHs (Non N-group). Two of three VHHs selected from non N-group VHHs showed sufficient antigen binding ability. These results suggested that biopanning followed by HTS provided a useful method for finding minor and diverse antigen-specific clones that could not be identified by conventional biopanning. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  4. Marked differences in human melanoma antigen-specific T cell responsiveness after vaccination using a functional microarray.

    Directory of Open Access Journals (Sweden)

    Daniel S Chen

    2005-10-01

    Full Text Available In contrast to many animal model studies, immunotherapeutic trials in humans suffering from cancer invariably result in a broad range of outcomes, from long-lasting remissions to no discernable effect.In order to study the T cell responses in patients undergoing a melanoma-associated peptide vaccine trial, we have developed a high-throughput method using arrays of peptide-major histocompatibility complexes (pMHC together with antibodies against secreted factors. T cells were specifically immobilized and activated by binding to particular pMHCs. The antibodies, spotted together with the pMHC, specifically capture cytokines secreted by the T cells. This technique allows rapid, simultaneous isolation and multiparametric functional characterization of antigen-specific T cells present in clinical samples. Analysis of CD8+ lymphocytes from ten melanoma patients after peptide vaccination revealed a diverse set of patient- and antigen-specific profiles of cytokine secretion, indicating surprising differences in their responsiveness. Four out of four patients who showed moderate or greater secretion of both interferon-gamma (IFNgamma and tumor necrosis factor-alpha (TNFalpha in response to a gp100 antigen remained free of melanoma recurrence, whereas only two of six patients who showed discordant secretion of IFNgamma and TNFalpha did so.Such multiparametric analysis of T cell antigen specificity and function provides a valuable tool with which to dissect the molecular underpinnings of immune responsiveness and how this information correlates with clinical outcome.

  5. The EPED pedestal model and edge localized mode-suppressed regimes: Studies of quiescent H-mode and development of a model for edge localized mode suppression via resonant magnetic perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, P. B.; Osborne, T. H.; Burrell, K. H.; Groebner, R. J.; Leonard, A. W.; Wade, M. R. [General Atomics, P.O. Box 85608, San Diego, California 92186-5608 (United States); Nazikian, R. [Princeton Plasma Physics Laboratory, Princeton, New Jersey (United States); Orlov, D. M. [University of California-San Diego, San Diego, California 92093 (United States); Schmitz, O. [Institut fuer Plasmaphysik, Forschungszentrum Juelich GmbH, Association FZJ-EURATOM, Juelich (Germany); Wilson, H. R. [York Plasma Institute, Department of Physics, University of York, Heslington, York YO10 5DD (United Kingdom)

    2012-05-15

    The EPED model predicts the H-mode pedestal height and width based upon two fundamental and calculable constraints: (1) onset of non-local peeling-ballooning modes at low to intermediate mode number, (2) onset of nearly local kinetic ballooning modes at high mode number. We present detailed tests of the EPED model in discharges with edge localized modes (ELMs), employing new high resolution measurements, and finding good quantitative agreement across a range of parameters. The EPED model is then applied for the first time to quiescent H-mode (QH), finding a similar level of agreement between predicted and observed pedestal height and width, and suggesting that the model can be used to predict the critical density for QH-mode operation. Finally, the model is applied toward understanding the suppression of ELMs with 3D resonant magnetic perturbations (RMP). Combining EPED with plasma response physics, a new working model for RMP ELM suppression is developed. We propose that ELMs are suppressed when a 'wall' associated with the RMP blocks the inward penetration of the edge transport barrier. A calculation of the required location of this 'wall' with EPED is consistent with observed profile changes during RMP ELM suppression and offers an explanation for the observed dependence on safety factor (q{sub 95}).

  6. Current treatment of rheumatoid arthritis. Perspectives for the development of antigen-specific therapies

    OpenAIRE

    Barberá, Ariana; Lorenzo, Noraylis; Domínguez, María del Carmen

    2012-01-01

    Rheumatoid arthritis is a degenerative disease characterized by chronic inflammation of peripheral joints. The first line of treatment involves the use of potent anti-inflammatory and immunosuppressive drugs, leading to an overall suppression of the immune system. However, these drugs do not induce sustained remission and their use can cause immunosuppression that leads to severe complications. Thus, there is a need for developing new therapeutic alternatives for the treatment of this disease...

  7. Poppers: more evidence of suppressed immunity.

    Science.gov (United States)

    James, J S

    1999-08-20

    Evidence from studies in mice shows that exposure to isobutyl nitrite suppresses the immune system. This immune suppression allows for bacterial growth in the lungs and livers of infected mice and can inhibit the ability of mediastinal lymph nodes to respond to antigen-specific stimulation. The mechanism for immune suppression may be a reduction in CD4+ and CD8+ T cell populations in the mediastinal lymph nodes following pulmonary infection with Listeria monocytogenes.

  8. Role of 4-1BB receptor in the control played by CD8(+ T cells on IFN-gamma production by Mycobacterium tuberculosis antigen-specific CD4(+ T Cells.

    Directory of Open Access Journals (Sweden)

    Carla Palma

    Full Text Available BACKGROUND: Antigen-specific IFN-gamma producing CD4(+ T cells are the main mediators of protection against Mycobacterium tuberculosis infection both under natural conditions and following vaccination. However these cells are responsible for lung damage and poor vaccine efficacy when not tightly controlled. Discovering new tools to control nonprotective antigen-specific IFN-gamma production without affecting protective IFN-gamma is a challenge in tuberculosis research. METHODS AND FINDINGS: Immunization with DNA encoding Ag85B, a candidate vaccine antigen of Mycobacterium tuberculosis, elicited in mice a low but protective CD4(+ T cell-mediated IFN-gamma response, while in mice primed with DNA and boosted with Ag85B protein a massive increase in IFN-gamma response was associated with loss of protection. Both protective and non-protective Ag85B-immunization generated antigen-specific CD8(+ T cells which suppressed IFN-gamma-secreting CD4(+ T cells. However, ex vivo ligation of 4-1BB, a member of TNF-receptor super-family, reduced the massive, non-protective IFN-gamma responses by CD4(+ T cells in protein-boosted mice without affecting the low protective IFN-gamma-secretion in mice immunized with DNA. This selective inhibition was due to the induction of 4-1BB exclusively on CD8(+ T cells of DNA-primed and protein-boosted mice following Ag85B protein stimulation. The 4-1BB-mediated IFN-gamma inhibition did not require soluble IL-10, TGF-beta, XCL-1 and MIP-1beta. In vivo Ag85B stimulation induced 4-1BB expression on CD8(+ T cells and in vivo 4-1BB ligation reduced the activation, IFN-gamma production and expansion of Ag85B-specific CD4(+ T cells of DNA-primed and protein-boosted mice. CONCLUSION/SIGNIFICANCE: Antigen-specific suppressor CD8(+ T cells are elicited through immunization with the mycobacterial antigen Ag85B. Ligation of 4-1BB receptor further enhanced their suppressive activity on IFN-gamma-secreting CD4(+ T cells. The selective

  9. Hierarchical Bayesian mixture modelling for antigen-specific T-cell subtyping in combinatorially encoded flow cytometry studies

    DEFF Research Database (Denmark)

    Lin, Lin; Chan, Cliburn; Hadrup, Sine R

    2013-01-01

    subtype identification in this novel, general model framework, and provide a detailed example using simulated data. We then describe application to a data set from an experimental study of antigen-specific T-cell subtyping using combinatorially encoded assays in human blood samples. Summary comments...... profiling in many biological areas, traditional flow cytometry measures relative levels of abundance of marker proteins using fluorescently labeled tags that identify specific markers by a single-color. One specific and important recent development in this area is the use of combinatorial marker assays...

  10. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    KAUST Repository

    Domina, Maria; Lanza Cariccio, Veronica; Benfatto, Salvatore; D'Aliberti, Deborah; Venza, Mario; Borgogni, Erica; Castellino, Flora; Biondo, Carmelo; D'Andrea, Daniel; Grassi, Luigi; Tramontano, Anna; Teti, Giuseppe; Felici, Franco; Beninati, Concetta

    2014-01-01

    There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  11. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    Directory of Open Access Journals (Sweden)

    Maria Domina

    Full Text Available There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  12. Rapid profiling of the antigen regions recognized by serum antibodies using massively parallel sequencing of antigen-specific libraries.

    KAUST Repository

    Domina, Maria

    2014-12-04

    There is a need for techniques capable of identifying the antigenic epitopes targeted by polyclonal antibody responses during deliberate or natural immunization. Although successful, traditional phage library screening is laborious and can map only some of the epitopes. To accelerate and improve epitope identification, we have employed massive sequencing of phage-displayed antigen-specific libraries using the Illumina MiSeq platform. This enabled us to precisely identify the regions of a model antigen, the meningococcal NadA virulence factor, targeted by serum antibodies in vaccinated individuals and to rank hundreds of antigenic fragments according to their immunoreactivity. We found that next generation sequencing can significantly empower the analysis of antigen-specific libraries by allowing simultaneous processing of dozens of library/serum combinations in less than two days, including the time required for antibody-mediated library selection. Moreover, compared with traditional plaque picking, the new technology (named Phage-based Representation OF Immuno-Ligand Epitope Repertoire or PROFILER) provides superior resolution in epitope identification. PROFILER seems ideally suited to streamline and guide rational antigen design, adjuvant selection, and quality control of newly produced vaccines. Furthermore, this method is also susceptible to find important applications in other fields covered by traditional quantitative serology.

  13. Increasing a Robust Antigen-Specific Cytotoxic T Lymphocyte Response by FMDV DNA Vaccination with IL-9 Expressing Construct

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    Qiang Zou

    2010-01-01

    Full Text Available Various chemokines and cytokines as adjuvants can be used to improve efficacy of DNA vaccination. In this study, we sought to investigate if a DNA construct expressing IL-9 (designed as proV-IL9 as a molecular adjuvant enhance antigen specific immune responses elicited by the pcD-VP1 DNA vaccination. Mice immunized with pcD-VP1 combined with proV-IL9 developed a strong humoral response. In addition, the coinoculation induced significant higher level of antigen-specific cell proliferation and cytotoxic response. This agreed well with higher expression level of IFN-γ and perforin in CD8+ T cells, but not with IL-17 in these T cells. The results indicate that IL-9 induces the development of IFN-γ-producing CD8+ T cells (Tc1, but not the IL-17-producing CD8+ T cells (Tc17. Up-regulated expressions of BCL-2 and BCL-XL were exhibited in these Tc1 cells, suggesting that IL-9 may trigger antiapoptosis mechanism in these cells. Together, these results demonstrated that IL-9 used as molecular adjuvant could enhance the immunogenicity of DNA vaccination, in augmenting humoral and cellular responses and particularly promoting Tc1 activations. Thus, the IL-9 may be utilized as a potent Tc1 adjuvant for DNA vaccines.

  14. Clonal analysis of T-cell responses to herpes simplex virus: isolation, characterization and antiviral properties of an antigen-specific helper T-cell clone.

    Science.gov (United States)

    Leung, K N; Nash, A A; Sia, D Y; Wildy, P

    1984-12-01

    A herpes simplex virus (HSV)-specific long-term T-cell clone has been established from the draining lymph node cells of BALB/c mice; the cells required repeated in vitro restimulation with UV-irradiated virus. The established T-cell clone expresses the Thy-1 and Lyt-1+2,3- surface antigens. For optimal proliferation of the cloned cells, both the presence of specific antigen and an exogenous source of T-cell growth factor are required. The proliferative response of the cloned T cells was found to be virus-specific but it did not distinguish between HSV-1 and HSV-2. Adoptive cell transfer of the cloned T cells helped primed B cells to produce anti-herpes antibodies: the response was antigen-specific and cell dose-dependent. The clone failed to produce a significant DTH reaction in vivo, but did produce high levels of macrophage-activating factor. Furthermore, the T-cell clone could protect from HSV infection, as measured by a reduction in local virus growth, and by enhanced survival following the challenge of mice with a lethal dose of virus. The mechanism(s) whereby this clone protects in vivo is discussed.

  15. Variable Domain N-Linked Glycans Acquired During Antigen-Specific Immune Responses Can Contribute to Immunoglobulin G Antibody Stability

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    Fleur S. van de Bovenkamp

    2018-04-01

    Full Text Available Immunoglobulin G (IgG can contain N-linked glycans in the variable domains, the so-called Fab glycans, in addition to the Fc glycans in the CH2 domains. These Fab glycans are acquired following introduction of N-glycosylation sites during somatic hypermutation and contribute to antibody diversification. We investigated whether Fab glycans may—in addition to affecting antigen binding—contribute to antibody stability. By analyzing thermal unfolding profiles of antibodies with or without Fab glycans, we demonstrate that introduction of Fab glycans can improve antibody stability. Strikingly, removal of Fab glycans naturally acquired during antigen-specific immune responses can deteriorate antibody stability, suggesting in vivo selection of stable, glycosylated antibodies. Collectively, our data show that variable domain N-linked glycans acquired during somatic hypermutation can contribute to IgG antibody stability. These findings indicate that introducing Fab glycans may represent a mechanism to improve therapeutic/diagnostic antibody stability.

  16. Tracking by flow cytometry antigen-specific follicular helper T cells in wild-type animals after protein vaccination.

    Science.gov (United States)

    Chakarov, Svetoslav; Fazilleau, Nicolas

    2015-01-01

    Flow cytometry is a valuable technology used in immunology to characterize and enumerate the different cell subpopulations specific for a nonself-antigen in the context of an ongoing immune response. Among them, follicular helper T cells are the cognate regulators of B cells in secondary lymphoid tissues. Thus, tracking them is of high interest especially in the context of protein vaccination. For this purpose, transgenic antigen-receptor mouse models have been largely used. It is now clear that transgenic models are not always the best means to study the dynamics of the immune response since they can modify the response. In this chapter, we describe how to track endogenous antigen-specific follicular helper T cells by flow cytometry after protein vaccination in nonmodified wild-type animals, which ultimately provides a comprehensive way to enumerate, characterize, and isolate these particular cells in vivo.

  17. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

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    Marcela V Maus

    2016-01-01

    Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

  18. Nod2 is required for antigen-specific humoral responses against antigens orally delivered using a recombinant Lactobacillus vaccine platform.

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    Sara A Bumgardner

    Full Text Available Safe and efficacious orally-delivered mucosal vaccine platforms are desperately needed to combat the plethora of mucosally transmitted pathogens. Lactobacillus spp. have emerged as attractive candidates to meet this need and are known to activate the host innate immune response in a species- and strain-specific manner. For selected bacterial isolates and mutants, we investigated the role of key innate immune pathways required for induction of innate and subsequent adaptive immune responses. Co-culture of murine macrophages with L. gasseri (strain NCK1785, L. acidophilus (strain NCFM, or NCFM-derived mutants-NCK2025 and NCK2031-elicited an M2b-like phenotype associated with TH2 skewing and immune regulatory function. For NCFM, this M2b phenotype was dependent on expression of lipoteichoic acid and S layer proteins. Through the use of macrophage genetic knockouts, we identified Toll-like receptor 2 (TLR2, the cytosolic nucleotide-binding oligomerization domain containing 2 (NOD2 receptor, and the inflammasome-associated caspase-1 as contributors to macrophage activation, with NOD2 cooperating with caspase-1 to induce inflammasome derived interleukin (IL-1β in a pyroptosis-independent fashion. Finally, utilizing an NCFM-based mucosal vaccine platform with surface expression of human immunodeficiency virus type 1 (HIV-1 Gag or membrane proximal external region (MPER, we demonstrated that NOD2 signaling is required for antigen-specific mucosal and systemic humoral responses. We show that lactobacilli differentially utilize innate immune pathways and highlight NOD2 as a key mediator of macrophage function and antigen-specific humoral responses to a Lactobacillus acidophilus mucosal vaccine platform.

  19. Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and anti-tumor effects

    Science.gov (United States)

    Osada, Takuya; Berglund, Peter; Morse, Michael A.; Hubby, Bolyn; Lewis, Whitney; Niedzwiecki, Donna; Hobeika, Amy; Burnett, Bruce; Devi, Gayathri R.; Clay, Timothy M.; Smith, Jonathan; Lyerly, H. Kim

    2013-01-01

    We recently demonstrated that Venezuelan equine encephalitis (VEE) virus-based replicon particles (VRP) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP expressing Interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and anti-tumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)) and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12 and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing anti-tumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted. PMID:22488274

  20. Suppression of large edge-localized modes in high-confinement DIII-D plasmas with a stochastic magnetic boundary.

    Science.gov (United States)

    Evans, T E; Moyer, R A; Thomas, P R; Watkins, J G; Osborne, T H; Boedo, J A; Doyle, E J; Fenstermacher, M E; Finken, K H; Groebner, R J; Groth, M; Harris, J H; La Haye, R J; Lasnier, C J; Masuzaki, S; Ohyabu, N; Pretty, D G; Rhodes, T L; Reimerdes, H; Rudakov, D L; Schaffer, M J; Wang, G; Zeng, L

    2004-06-11

    A stochastic magnetic boundary, produced by an applied edge resonant magnetic perturbation, is used to suppress most large edge-localized modes (ELMs) in high confinement (H-mode) plasmas. The resulting H mode displays rapid, small oscillations with a bursty character modulated by a coherent 130 Hz envelope. The H mode transport barrier and core confinement are unaffected by the stochastic boundary, despite a threefold drop in the toroidal rotation. These results demonstrate that stochastic boundaries are compatible with H modes and may be attractive for ELM control in next-step fusion tokamaks.

  1. Application of Adoptive T-Cell Therapy Using Tumor Antigen-Specific T-Cell Receptor Gene Transfer for the Treatment of Human Leukemia

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    Toshiki Ochi

    2010-01-01

    Full Text Available The last decade has seen great strides in the field of cancer immunotherapy, especially the treatment of melanoma. Beginning with the identification of cancer antigens, followed by the clinical application of anti-cancer peptide vaccination, it has now been proven that adoptive T-cell therapy (ACT using cancer antigen-specific T cells is the most effective option. Despite the apparent clinical efficacy of ACT, the timely preparation of a sufficient number of cancer antigen-specific T cells for each patient has been recognized as its biggest limitation. Currently, therefore, attention is being focused on ACT with engineered T cells produced using cancer antigen-specific T-cell receptor (TCR gene transfer. With regard to human leukemia, ACT using engineered T cells bearing the leukemia antigen-specific TCR gene still remains in its infancy. However, several reports have provided preclinical data on TCR gene transfer using Wilms' tumor gene product 1 (WT1, and also preclinical and clinical data on TCR gene transfer involving minor histocompatibility antigen, both of which have been suggested to provide additional clinical benefit. In this review, we examine the current status of anti-leukemia ACT with engineered T cells carrying the leukemia antigen-specific TCR gene, and discuss the existing barriers to progress in this area.

  2. A novel dendritic cell-based direct ex vivo assay for detection and enumeration of circulating antigen-specific human T cells.

    Science.gov (United States)

    Carrio, Roberto; Zhang, Ge; Drake, Donald R; Schanen, Brian C

    2018-05-07

    Although a variety of assays have been used to examine T cell responses in vitro, standardized ex vivo detection of antigen-specific CD4 + T cells from human circulatory PBMCs remains constrained by low-dimensional characterization outputs and the need for polyclonal, mitogen-induced expansion methods to generate detectable response signals. To overcome these limitations, we developed a novel methodology utilizing antigen-pulsed autologous human dendritic target cells in a rapid and sensitive assay to accurately enumerate antigen-specific CD4 + T cell precursor frequency by multiparametric flow cytometry. With this approach, we demonstrate the ability to reproducibly quantitate poly-functional T cell responses following both primary and recall antigenic stimulation. Furthermore, this approach enables more comprehensive phenotypic profiling of circulating antigen-specific CD4 + T cells, providing valuable insights into the pre-existing polarization of antigen-specific T cells in humans. Combined, this approach permits sensitive and detailed ex vivo detection of antigen-specific CD4 + T cells delivering an important tool for advancing vaccine, immune-oncology and other therapeutic studies.

  3. Passive Newtonian noise suppression for gravitational-wave observatories based on shaping of the local topography

    Science.gov (United States)

    Harms, Jan; Hild, Stefan

    2014-09-01

    In this article we propose a new method for reducing Newtonian noise (NN) in laser-interferometric gravitational wave detectors located on the Earth's surface. We show that by excavating meter-scale recesses in the ground around the main test masses of a gravitational wave detector it is possible to reduce the coupling of Rayleigh wave driven seismic disturbances to test mass displacement. A discussion of the optimal recess shape is given and we use finite element simulations to derive the scaling of the NN suppression with the parameters of the recess as well as the frequency of the seismic excitation. Considering an interferometer similar to an Advance LIGO configuration, our simulations indicate a frequency dependent NN suppression factor of 2-4 in the relevant frequency range for a recesses of 4 m depth and a width and length of 11 m and 5 m, respectively. Though a retrofit to existing interferometers seems not impossible, the application of our concept to future infrastructures seems to provide a better benefit/cost ratio and therefore a higher feasibility.

  4. Passive Newtonian noise suppression for gravitational-wave observatories based on shaping of the local topography

    International Nuclear Information System (INIS)

    Harms, Jan; Hild, Stefan

    2014-01-01

    In this article we propose a new method for reducing Newtonian noise (NN) in laser-interferometric gravitational wave detectors located on the Earth's surface. We show that by excavating meter-scale recesses in the ground around the main test masses of a gravitational wave detector it is possible to reduce the coupling of Rayleigh wave driven seismic disturbances to test mass displacement. A discussion of the optimal recess shape is given and we use finite element simulations to derive the scaling of the NN suppression with the parameters of the recess as well as the frequency of the seismic excitation. Considering an interferometer similar to an Advance LIGO configuration, our simulations indicate a frequency dependent NN suppression factor of 2–4 in the relevant frequency range for a recesses of 4 m depth and a width and length of 11 m and 5 m, respectively. Though a retrofit to existing interferometers seems not impossible, the application of our concept to future infrastructures seems to provide a better benefit/cost ratio and therefore a higher feasibility. (paper)

  5. Induction of an antigen specific gut inflammatory reaction in mice and rats: a model for human Inflammatory Bowel Disease

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    Gerlinde Agate Platais Brasil Teixeira

    2009-06-01

    Full Text Available Food allergy is an adverse reaction that occurs in susceptible people when they eat sensitizing foods and is one of the causes of Inflammatory Bowel Disease (IBD. The effort to understand the induction process of these diseases is important as IBD is increasing worldwide, including in Brazil. The aim of this study was to develop an experimental antigen specific inflammatory process of the gut of mice and rats, using peanut seeds. Animals were immunized with peanut protein extract before their exposure to the in natura peanut seeds. Results showed that systemic immunization with peanut protein extracts rendered significantly higher antibody titers than control groups and that immunized animals submitted to a challenge diet containing peanuts presented time dependent alterations of the gut similar to celiac disease. In conclusion, results suggested that this experimental model was a convenient tool to study the evolution of alterations in chronic antigen specific gut inflammatory process.A alergia alimentar consiste em uma reação adversa que ocorre em pessoas susceptíveis quando ingerem alimentos sensibilizantes, sendo uma das causas das Doenças Inflamatórias Intestinais (IBD. O objetivo deste estudo foi desenvolver um protocolo experimental de indução de um processo inflamatório intestinal antígeno-específico em camundongos e ratos. Foi escolhida para a indução deste processo a semente de amendoim. Os animais foram imunizados com o extrato protéico previamente à exposição com a semente in natura. Nossos resultados mostram que a imunização sistêmica com extratos protéicos de amendoim ocasiona títulos significativamente maiores de anticorpos quando comparado ao grupo controle e que os animais imunizados submetidos ao desafio com a dieta contendo exclusivamente amendoim apresentam alterações intestinais tempo-dependente similares àquelas observadas na doença celíaca. Os resultados obtidos sugerem que este modelo

  6. Functional, Antigen-Specific Stem Cell Memory (TSCM CD4+ T Cells Are Induced by Human Mycobacterium tuberculosis Infection

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    Cheleka A. M. Mpande

    2018-03-01

    Full Text Available BackgroundMaintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM, which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM or effector (TEFF T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM. We aimed to determine if infection with Mycobacterium tuberculosis (M. tb, the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology.MethodsWe studied T cell responses to natural M. tb infection in a longitudinal adolescent cohort of recent QuantiFERON-TB Gold (QFT converters and three cross-sectional QFT+ adult cohorts; and to bacillus Calmette–Guerin (BCG vaccination in infants. M. tb and/or BCG-specific CD4 T cells were detected by flow cytometry using major histocompatibility complex class II tetramers bearing Ag85, CFP-10, or ESAT-6 peptides, or by intracellular cytokine staining. Transcriptomic analyses of M. tb-specific tetramer+ CD4+ TSCM (CD45RA+ CCR7+ CD27+ were performed by microfluidic qRT-PCR, and functional and phenotypic characteristics were confirmed by measuring expression of chemokine receptors, cytotoxic molecules and cytokines using flow cytometry.ResultsM. tb-specific TSCM were not detected in QFT-negative persons. After QFT conversion frequencies of TSCM increased to measurable levels and remained detectable thereafter, suggesting that primary M. tb infection induces TSCM cells. Gene expression (GE profiling of tetramer+ TSCM showed that these cells were distinct from bulk CD4+ naïve T cells (TN and shared features of bulk TSCM and M. tb-specific tetramer+ TCM and TEFF cells. These TSCM were predominantly CD95+ and CXCR3+, markers typical of CD8+ TSCM. Tetramer+ TSCM expressed significantly higher protein levels of CCR5, CCR6, CXCR3, granzyme A, granzyme K, and granulysin than bulk TN and TSCM cells. M. tb-specific TSCM were also

  7. Enhanced Dendritic Cell-Mediated Antigen-Specific CD4+ T Cell Responses: IFN-Gamma Aids TLR Stimulation

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    Kuo-Ching Sheng

    2013-01-01

    Full Text Available Phenotypic maturation and T cell stimulation are two functional attributes of DCs critical for immune induction. The combination of antigens, including those from cancer, with Toll-like receptor (TLR ligands induces far superior cellular immune responses compared to antigen alone. In this study, IFN-gamma treatment of bone marrow-derived DC, followed by incubation with the TLR2, TLR4, or TLR9 agonists, enhanced DC activation compared to TLR ligation alone. Most notably, the upregulation of CD40 with LPS stimulation and CD86 with CpG stimulation was observed in in vitro cultures. Similarly, IFN-gamma coinjected with TLR ligands was able to promote DC activation in vivo, with DCs migrating from the site of immunization to the popliteal lymph nodes demonstrating increased expression of CD80 and CD86. The heightened DC activation translated to a drastic increase in T cell stimulatory capacity in both antigen independent and antigen dependent fashions. This is the first time that IFN-gamma has been shown to have a combined effect with TLR ligation to enhance DC activation and function. The results demonstrate the novel use of IFN-gamma together with TLR agonists to enhance antigen-specific T cell responses, for applications in the development of enhanced vaccines and drug targets against diseases including cancer.

  8. Effect of operating conditions in production of diagnostic Salmonella Enteritidis O-antigen-specific monoclonal antibody in different bioreactor systems.

    Science.gov (United States)

    Ayyildiz-Tamis, Duygu; Nalbantsoy, Ayse; Elibol, Murat; Deliloglu-Gurhan, Saime Ismet

    2014-01-01

    In this study, different cultivation systems such as roller bottles (RB), 5-L stirred-tank bioreactor (STR), and disposable bioreactors were used to cultivate hybridoma for lab-scale production of Salmonella Enteritidis O-antigen-specific monoclonal antibody (MAb). Hybridoma cell line was cultivated in either serum-containing or serum-free medium (SFM) culture conditions. In STR, MAb production scaled up to 4 L, and production capabilities of the cells were also evaluated in different featured production systems. Moreover, the growth parameters of the cells in all production systems such as glucose consumption, lactate and ammonia production, and also MAb productivities were determined. Collected supernatants from the reactors were concentrated by a cross-flow filtration system. In conclusion, cells were not adapted to SFM in RB and STR. Therefore, less MAb titer in both STR and RB systems with SFM was observed compared to the cultures containing fetal bovine serum-supplemented medium. A higher MAb titer was gained in the membrane-aerated system compared to those in STR and RB. Although the highest MAb titer was obtained in the static membrane bioreactor system, the highest productivity was obtained in STR operated in semicontinuous mode with overlay aeration.

  9. Adoptive Immunotherapy for Hematological Malignancies Using T Cells Gene-Modified to Express Tumor Antigen-Specific Receptors

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    Hiroshi Fujiwara

    2014-12-01

    Full Text Available Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as “cellular drugs”. As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs, transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy.

  10. Splenic B cells and antigen-specific B cells process anti-Ig in a similar manner

    International Nuclear Information System (INIS)

    Myers, C.D.; Vitetta, E.S.

    1989-01-01

    B lymphocytes can process and present antigen to T cells. However, the fate of native antigen after its binding to specific B cells, i.e., the intracellular events involved in the processing and recycling of the antigenic fragments to the cell surface for antigen presentation, are not well understood. In the present study, we demonstrate that murine B cells degrade anti-Ig molecules bound to their surface and release acid soluble fragments into the supernatant. We also demonstrate that the kinetics of this process are identical for anti-mu, anti-delta, and anti-light chain antibodies, indicating that both surface IgM and surface IgD are equally effective in binding antigen and directing its processing. We also describe the effects of azide, chloroquine, and irradiation on this process. To extend these studies to the processing of specifically bound antigen, we demonstrate that highly purified trinitrophenyl antigen-binding cells degrade anti-Ig molecules with the same kinetics as unpurified splenic B cells. Thus, this purified population provides a suitable model system for the analysis of antigen degradation by antigen-specific cells

  11. Antigen-specific IL-23/17 pathway activation by murine semi-mature DC-like cells

    Energy Technology Data Exchange (ETDEWEB)

    Nagasaka, Shinya; Iwasaki, Takumi; Okano, Tomoko [Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510 (Japan); Chiba, Joe, E-mail: chibaj@rs.noda.tus.ac.jp [Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510 (Japan)

    2009-09-11

    We analyzed the phenotype and function of bone marrow-derived dendritic cells (DCs) induced in vitro without using any serum during the late stage of cultivation. These 'serum-free' DCs (SF-DCs) possessed the ability to induce T cell proliferation as well as antibody responses, indicating that they were functional DCs. Surprisingly, the SF-DCs akin to semi-mature DCs in terms of both phenotypic and functional characteristics. The SF-DCs did not produce IL-12 but produced large amounts of IL-23 following lipopolysaccharide stimulation. The antigen-specific production of IL-17 by CD4{sup +} T cells co-cultured with OVA-loaded SF-DCs was significantly higher than that with OVA-loaded conventional DCs. These results suggest that SF-DCs tend to produce IL-23 and can consequently induce the IL-17 producing CD4{sup +} T cells. The semi-mature DC-like cells reported here will be useful vehicles for DC immunization and might contribute to studies on the possible involvement of semi-mature DCs in Th17 cell differentiation.

  12. Characterizing complex polysera produced by antigen-specific immunization through the use of affinity-selected mimotopes.

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    Galina Denisova

    Full Text Available BACKGROUND: Antigen-based (as opposed to whole organism vaccines are actively being pursued for numerous indications. Even though different formulations may produce similar levels of total antigen-specific antibody, the composition of the antibody response can be quite distinct resulting in different levels of therapeutic activity. METHODOLOGY/PRINCIPAL FINDINGS: Using plasmid-based immunization against the proto-oncogene HER-2 as a model, we have demonstrated that affinity-selected epitope mimetics (mimotopes can provide a defined signature of a polyclonal antibody response. Further, using novel computer algorithms that we have developed, these mimotopes can be used to predict epitope targets. CONCLUSIONS/SIGNIFICANCE: By combining our novel strategy with existing methods of epitope prediction based on physical properties of an individual protein, we believe that this method offers a robust method for characterizing the breadth of epitope-specificity within a specific polyserum. This strategy is useful as a tool for monitoring immunity following vaccination and can also be used to define relevant epitopes for the creation of novel vaccines.

  13. Fluorescently labeled dengue viruses as probes to identify antigen-specific memory B cells by multiparametric flow cytometry.

    Science.gov (United States)

    Woda, Marcia; Mathew, Anuja

    2015-01-01

    Low frequencies of memory B cells in the peripheral blood make it challenging to measure the functional and phenotypic characteristics of this antigen experienced subset of B cells without in vitro culture. To date, reagents are lacking to measure ex vivo frequencies of dengue virus (DENV)-specific memory B cells. We wanted to explore the possibility of using fluorescently labeled DENV as probes to detect antigen-specific memory B cells in the peripheral blood of DENV immune individuals. Alexa Fluor dye-labeled DENV yielded viable virus that could be stored at -80°C for long periods of time. Using a careful gating strategy and methods to decrease non-specific binding, we were able to identify a small frequency of B cells from dengue immune individuals that bound labeled DENV. Sorted DENV(+) B cells from immune, but not naïve donors secreted antibodies that bound DENV after in vitro stimulation. Overall, Alexa Fluor dye-labeled DENVs are useful reagents to enable the detection and characterization of memory B cells in DENV immune individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity

    Science.gov (United States)

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-07-01

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

  15. Suppression of the reactive hyperemic response in the forearm due to local hand cooling.

    Science.gov (United States)

    Kilgour, R D; Carranza, A; Findlay, R

    1997-01-01

    Forearm blood flow (FBF) was measured by electrical impedance plethysmography in order to identify the influence of local cooling of the contralateral hand after 3 min of arterial occlusion. Ten volunteers (six females, four males) were randomly assigned to the following three experimental conditions on separate days: a) 6 min of local hand cooling (5-7 degrees C); b) 3 min of arterial occlusion of the forearm; and c) combined arterial occlusion and local cooling. All subjects experienced the typical pressor response during 6 min of hand cooling as evidenced by the significant increase (p forearm vascular resistance (FVR = MAP/FBF) made an initial drop during the first 30 s of cooling and then gradually rose to reach peak levels between 5-6 min of cooling. With respect to the hyperemic response, FBF significantly increased (p cooling, FBF increased above baseline values and reached peak levels during the initial 30 s of the post-occlusion period. However, the magnitude of the hyperemic response was significantly lower in the cold condition compared to the hyperemia alone (3.20 +/- 0.42 vs 6.75 +/- 0.64 ml x 100 ml-1.min-1; p cooling had an overriding effect on the factors that promote peripheral vasodilation following brief periods (3 min) of arterial occlusion.

  16. Suppression of large edge localized modes with edge resonant magnetic fields in high confinement DIII-D plasmas

    International Nuclear Information System (INIS)

    Thomas, P.R.; Becoulet, M.; Evans, T.E.; Osborne, T.H.; Groebner, R.J.; Jackson, G.L.; Haye, R.J. La; Schaffer, M.J.; West, W.P.; Moyer, R.A.; Rhodes, T.L.; Rudakov, D.L.; Watkins, J.G.; Boedo, J.A.; Doyle, E.J.; Wang, G.; Zeng, L.; Fenstermacher, M.E.; Groth, M.; Lasnier, C.J.; Finken, K.H.; Harris, J.H.; Pretty, D.G.; Masuzaki, S.; Ohyabu, N.; Reimerdes, H.; Wade, M.R.

    2005-01-01

    Large divertor heat pulses due to Type-I edge localized modes (ELMs) have been eliminated reproducibly in DIII-D with small dc currents driven in a simple magnetic perturbation coil. The current required to eliminate all but a few isolated Type-I ELMs, during a coil pulse, is less than 0.4% of plasma current. Modelling shows that the perturbation fields resonate with plasma flux surfaces across most of the pedestal region (0.9 ≤ N ≤ 1.0), when q95 = 3.7±0.2 creating small remnant magnetic islands surrounded by weakly stochastic field lines. The stored energy, N , H-mode quality factor and global energy confinement time are unaltered by the magnetic perturbation. At high collisionality (ν* ∼0.5-1), there is no obvious effect of the perturbation on the edge profiles and yet ELMs are suppressed, nearly completely, for up to 9τ E . At low collisionality (ν* <0.1), there is a density pump-out and complete ELM suppression, reminiscent of the DIIID QH- mode. Other differences, specifically in the resonance condition and the magnetic fluctuations, suggest that different mechanisms are at play in the different collisionality regimes. In addition to a description and interpretation of the DIIID data, the application of this method to ELM control on other machines, such as JET and ITER will be discussed. (author)

  17. Enumeration of antigen-specific CD8+ T lymphocytes by single-platform, HLA tetramer-based flow cytometry: a European multicenter evaluation.

    NARCIS (Netherlands)

    Heijnen, I.; Barnett, D.; Arroz, M.J.; Barry, S.M.; Bonneville, M.; Brando, B.; D'Hautcourt, J.L.; Kern, F.; Totterman, T.H.; Marijt, E.W.; Bossy, D.; Preijers, F.W.M.B.; Rothe, G.; Gratama, J.W.

    2004-01-01

    BACKGROUND: HLA class I peptide tetramers represent powerful diagnostic tools for detection and monitoring of antigen-specific CD8(+) T cells. The impetus for the current multicenter study is the critical need to standardize tetramer flow cytometry if it is to be implemented as a routine diagnostic

  18. Pedestal bifurcation and resonant field penetration at the threshold of edge-localized mode suppression in the DIII-D Tokamak.

    Science.gov (United States)

    Nazikian, R; Paz-Soldan, C; Callen, J D; deGrassie, J S; Eldon, D; Evans, T E; Ferraro, N M; Grierson, B A; Groebner, R J; Haskey, S R; Hegna, C C; King, J D; Logan, N C; McKee, G R; Moyer, R A; Okabayashi, M; Orlov, D M; Osborne, T H; Park, J-K; Rhodes, T L; Shafer, M W; Snyder, P B; Solomon, W M; Strait, E J; Wade, M R

    2015-03-13

    Rapid bifurcations in the plasma response to slowly varying n=2 magnetic fields are observed as the plasma transitions into and out of edge-localized mode (ELM) suppression. The rapid transition to ELM suppression is characterized by an increase in the toroidal rotation and a reduction in the electron pressure gradient at the top of the pedestal that reduces the perpendicular electron flow there to near zero. These events occur simultaneously with an increase in the inner-wall magnetic response. These observations are consistent with strong resonant field penetration of n=2 fields at the onset of ELM suppression, based on extended MHD simulations using measured plasma profiles. Spontaneous transitions into (and out of) ELM suppression with a static applied n=2 field indicate competing mechanisms of screening and penetration of resonant fields near threshold conditions. Magnetic measurements reveal evidence for the unlocking and rotation of tearinglike structures as the plasma transitions out of ELM suppression.

  19. Suppression of large edge localized modes with a stochastic magnetic boundary in high confinement DIII-D plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, P.R.; Boedo, J.A. [Association Euratom-CEA, Centre d' Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee; Evans, T.E.; Osborne, T.H.; Groebner, R.J.; La Haye, R.J.; Schaffer, M.J.; West, W.P. [General Atomic, San Diego (United States); Moyer, R.A.; Rudakov, D.L. [California Univ., San Diego, La Jolla, CA (United States); Watkins, J.G. [Sandia National Labs., Albuquerque, NM (United States); Fenstermacher, M.E.; Groth, M.; Lasnier, C.J. [Lawrence Livermore National Lab., CA (United States); Finken, K.H. [FZ-Julich Euratom Association, Julich (Germany); Harris, J.H.; Pretty, D.G. [Australian National Univ., Canberra, ACT (Australia); Masuzaki, S.; Ohyabu, N. [National Institute for Fusion Science, Gifu-ken (Japan); Rhodes, T.L.; Wang, G.; Zeng, L. [California Univ., Los Angeles, CA (United States); Reimerdes, H. [Columbia Univ., New York, NY (United States); Wade, M. [Oak Ridge National Lab., TN (United States)

    2004-07-01

    This work started from the point of view that a robust way of actively suppressing type I ELMs (edge localized modes) is both mandatory and practical in ITER. We report some considerable experimental success in exploring this proposition, using a magnetic perturbation generated by the I-coils in DIII-D. The hypothesis was tested that an external magnetic perturbation, whose toroidal and poloidal spectrum is in resonance with field lines at the edge, increases transport there, reduces the pressure gradient and, thereby, eliminates the drive for the MHD instabilities that cause ELMs. Holding the pressure gradient just below the threshold at which ELMs are triggered, should bring good fusion performance without the penalty of ELMs. (authors)

  20. The simultaneous ex vivo detection of low-frequency antigen-specific CD4+ and CD8+ T-cell responses using overlapping peptide pools.

    Science.gov (United States)

    Singh, Satwinder Kaur; Meyering, Maaike; Ramwadhdoebe, Tamara H; Stynenbosch, Linda F M; Redeker, Anke; Kuppen, Peter J K; Melief, Cornelis J M; Welters, Marij J P; van der Burg, Sjoerd H

    2012-11-01

    The ability to measure antigen-specific T cells at the single-cell level by intracellular cytokine staining (ICS) is a promising immunomonitoring tool and is extensively applied in the evaluation of immunotherapy of cancer. The protocols used to detect antigen-specific CD8+ T-cell responses generally work for the detection of antigen-specific T cells in samples that have undergone at least one round of in vitro pre-stimulation. Application of a common protocol but now using long peptides as antigens was not suitable to simultaneously detect antigen-specific CD8+ and CD4+ T cells directly ex vivo in cryopreserved samples. CD8 T-cell reactivity to monocytes pulsed with long peptides as antigens ranged between 5 and 25 % of that observed against monocytes pulsed with a direct HLA class I fitting minimal CTL peptide epitope. Therefore, we adapted our ICS protocol and show that the use of tenfold higher concentration of long peptides to load APC, the use of IFN-α and poly(I:C) to promote antigen processing and improve T-cell stimulation, does allow for the ex vivo detection of low-frequency antigen-specific CD8+ and CD4+ T cells in an HLA-independent setting. While most of the improvements were related to increasing the ability to measure CD8+ T-cell reactivity following stimulation with long peptides to at least 50 % of the response detected when using a minimal peptide epitope, the final analysis of blood samples from vaccinated patients successfully showed that the adapted ICS protocol also increases the ability to ex vivo detect low-frequency p53-specific CD4+ T-cell responses in cryopreserved PBMC samples.

  1. Longitudinal multiparameter single-cell analysis of macaques immunized with pneumococcal protein-conjugated or unconjugated polysaccharide vaccines reveals distinct antigen specific memory B cell repertoires.

    Directory of Open Access Journals (Sweden)

    Bin Jia

    Full Text Available The efficacy of protein-conjugated pneumococcal polysaccharide vaccines has been well characterized for children. The level of protection conferred by unconjugated polysaccharide vaccines remains less clear, particularly for elderly individuals who have had prior antigenic experience through immunization with unconjugated polysaccharide vaccines or natural exposure to Streptococcus pneumoniae.We compared the magnitude, diversity and genetic biases of antigen-specific memory B cells in two groups of adult cynomolgus macaques that were immunized with a 7-valent conjugated vaccine and boosted after five years with either a 13-valent pneumococcal polysaccharide conjugate vaccine (13vPnC or a 23-valent unconjugated pneumococcal polysaccharide vaccine (23vPS using microengraving (a single-cell analysis method and single-cell RT-PCR.Seven days after boosting, the mean frequency of antigen-specific memory B cells was significantly increased in macaques vaccinated with 13vPnC compared to those receiving 23vPS. The 13vPnC-vaccinated macaques also exhibited a more even distribution of antibody specificities to four polysaccharides in the vaccine (PS4, 6B, 14, 23F that were examined. However, single-cell analysis of the antibody variable region sequences from antigen-specific B cells elicited by unconjugated and conjugated vaccines indicated that both the germline gene segments forming the heavy chains and the average lengths of the Complementary Determining Region 3 (CDR3 were similar.Our results confirm that distinctive differences can manifest between antigen-specific memory B cell repertoires in nonhuman primates immunized with conjugated and unconjugated pneumococcal polysaccharide vaccines. The study also supports the notion that the conjugated vaccines have a favorable profile in terms of both the frequency and breadth of the anamnestic response among antigen-specific memory B cells.

  2. An inducible model of abacterial prostatitis induces antigen specific inflammatory and proliferative changes in the murine prostate

    Science.gov (United States)

    Haverkamp, Jessica M.; Charbonneau, Bridget; Meyerholz, David K.; Cohen, Michael B.; Snyder, Paul W.; Svensson, Robert U.; Henry, Michael D.; Wang, Hsing- Hui

    2011-01-01

    Background Prostatitis is a poorly understood disease and increasing evidence suggests inflammation is involved in other prostatic diseases, including prostate cancer. Methods The ability of pre-activated CD8 T cells to induce prostatitis was examined by adoptive transfer into POET-3 mice or POET-3/Luc/Pten−/+ mice. Characterization of the inflammatory response was determined by examining leukocyte infiltration by histological analysis, flow cytometry and by evaluating cytokine and chemokine levels in prostate tissue. The impact of inflammation on the prostate was evaluated by monitoring epithelial cell proliferation over time. Results Initiation of inflammation by ovalbumin specific CD8+ T cells (OT-I cells) resulted in development of acute prostatitis in the anterior, dorsolateral and anterior prostate of POET-3 and POET-3/Luc/Pten−/+ mice. Acute prostatitis was characterized by recruitment of adoptively transferred OT-I cells and importantly, autologous CD4+ and CD8+ T cells, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). In concert with leukocyte infiltration elevated levels of pro-inflammatory cytokines and chemokines were observed. Inflammation also resulted in marked epithelial cell proliferation that was sustained up to 80 days post adoptive-transfer of OT-I cells. Conclusions The POET-3 model represents a novel mouse model to study both acute and chronic prostate inflammation in an antigen-specific system. Further, the POET-3 mouse model can be crossed with other genetic models of disease such as the C57/Luc/Pten−/− model of prostate cancer, allowing the impact of prostatitis on other prostatic diseases to be evaluated. PMID:21656824

  3. Correlation between CD16a binding and immuno effector functionality of an antigen specific immunoglobulin Fc fragment (Fcab).

    Science.gov (United States)

    Kainer, Manuela; Antes, Bernhard; Wiederkum, Susanne; Wozniak-Knopp, Gordana; Bauer, Anton; Rüker, Florian; Woisetschläger, Max

    2012-10-15

    Antigen binding immunoglobulin Fc fragments (Fcab) are generated by engineering loop regions in the CH3 domain of human IgG1 Fc. Variants of an Fcab specific for Her-2 were designed to display either enhanced (S239D:A330L:I332E) or diminished (L234A:L235A) binding affinities to the Fc receptor CD16a based on mutations described previously. The two mutant Fcab proteins demonstrated the expected modulation of CD16a binding. Interaction with recombinant or cell surface expressed Her-2 was unaffected in both mutants compared to the parental Fcab. Binding affinities for CD16a correlated with the ADCC-potencies of the Fcab variants. Additional studies indicated that the L234A:L235A variant Fcab had equivalent structural features as the unmodified Fcab since their DSC profiles were similar and antigen binding after re-folding upon partial heat denaturation had not changed. Introduction of the S239D:A330L:I332E mutations resulted in a significant reduction of the CH2 domain melting temperature, a moderate decrease of the thermal transition of the CH3 domain and lower antigen binding after thermal stress compared to the parental Fcab. We conclude that the known correlation between CD16a binding affinity and ADCC potency is also valid in Fcab proteins and that antigen specific Fcab molecules can be further engineered for fine tuning of immuno effector functions. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Thermoresponsive nanocomposite gel for local drug delivery to suppress the growth of glioma by inducing autophagy.

    Science.gov (United States)

    Ding, Li; Wang, Qi; Shen, Ming; Sun, Ying; Zhang, Xiangyu; Huang, Can; Chen, Jianhua; Li, Rongxin; Duan, Yourong

    2017-07-03

    Although the treatments of malignant glioma include surgery, radiotherapy and chemotherapy by oral drug administration, the prognosis of patients with glioma remains very poor. We developed a polyethylene glycol-dipalmitoylphosphatidyle- thanoiamine (mPEG-DPPE) calcium phosphate nanoparticles (NPs) injectable thermoresponsive hydrogel (nanocomposite gel) that could provide a sustained and local delivery of paclitaxel (PTX) and temozolomide (TMZ). In addition, the proportion of PTX and TMZ for the optimal synergistic antiglioma effect on C6 cells was determined to be 1:100 (w/w) by the Chou and Talalay method. Our results clearly indicated that the autophagy induced by PTX:TMZ NPs plays an important role in regulating tumor cell death, while autophagy inhibition dramatically reverses the antitumor effect of PTX:TMZ NPs, suggesting that antiproliferative autophagy occurs in response to PTX:TMZ NPs treatment. The antitumor efficacy of the PTX:TMZ NP-loaded gel was evaluated in situ using C6 tumor-bearing rats, and the PTX:TMZ NP-loaded gel exhibited superior antitumor performance. The antitumor effects of the nanocomposite gel in vivo were shown to correlate with autophagic cell death in this study. The in vivo results further confirmed the advantages of such a strategy. The present study may provide evidence supporting the development of nanomedicine for potential clinical application.

  5. Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Tom L Schmidt

    2017-05-01

    Full Text Available Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2, we observed slow but steady spatial spread, at about 100-200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2 produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation.

  6. Changes in cluster magnetism and suppression of local superconductivity in amorphous FeCrB alloy irradiated by Ar"+ ions

    International Nuclear Information System (INIS)

    Okunev, V.D.; Samoilenko, Z.A.; Szymczak, H.; Szewczyk, A.; Szymczak, R.; Lewandowski, S.J.; Aleshkevych, P.; Malinowski, A.; Gierłowski, P.; Więckowski, J.; Wolny-Marszałek, M.; Jeżabek, M.; Varyukhin, V.N.; Antoshina, I.A.

    2016-01-01

    We show that cluster magnetism in ferromagnetic amorphous Fe_6_7Cr_1_8B_1_5 alloy is related to the presence of large, D=150–250 Å, α-(Fe Cr) clusters responsible for basic changes in cluster magnetism, small, D=30–100 Å, α-(Fe, Cr) and Fe_3B clusters and subcluster atomic α-(Fe, Cr, B) groupings, D=10–20 Å, in disordered intercluster medium. For initial sample and irradiated one (Φ=1.5×10"1"8 ions/cm"2) superconductivity exists in the cluster shells of metallic α-(Fe, Cr) phase where ferromagnetism of iron is counterbalanced by antiferromagnetism of chromium. At Φ=3×10"1"8 ions/cm"2, the internal stresses intensify and the process of iron and chromium phase separation, favorable for mesoscopic superconductivity, changes for inverse one promoting more homogeneous distribution of iron and chromium in the clusters as well as gigantic (twice as much) increase in density of the samples. As a result, in the cluster shells ferromagnetism is restored leading to the increase in magnetization of the sample and suppression of local superconductivity. For initial samples, the temperature dependence of resistivity ρ(T)~T"2 is determined by the electron scattering on quantum defects. In strongly inhomogeneous samples, after irradiation by fluence Φ=1.5×10"1"8 ions/cm"2, the transition to a dependence ρ(T)~T"1"/"2 is caused by the effects of weak localization. In more homogeneous samples, at Φ=3×10"1"8 ions/cm"2, a return to the dependence ρ(T)~T"2 is observed. - Highlights: • The samples at high dose of ion irradiation become more homogeneous. • Gigantic increase in density of the samples (twice as much) is observed. • Ferromagnetism in large Fe–Cr clusters is restored. • Ferromagnetism of Fe–Cr clusters suppresses local superconductivity in them. • The participation of quantum defects in scattering of electrons is returned.

  7. Suppression of antigen-specific antibody responses in mice exposed to perfluorooctanoic acid: Role of PPARa and T- and B-cell targeting

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dosing information, body weights during exposure and immune system endpoints. This dataset is associated with the following publication: DeWitt, J., W. Williams , J....

  8. Antigen-Specific lgA B Memory Cell Responses to Shigella Antigens Elicited in Volunteers Immunized with Live Attenuated Shigella flexneri 2a Oral Vaccine Candidates

    Science.gov (United States)

    2011-01-01

    167. [10] E.V. Oaks, T.L. Hale, S.B. Formal, Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella ...cell responses to Shigella antigens elicited in volunteers immunized with live attenuated Shigella flexneri 2a oral vaccine candidates J.K. Simona,b... Shigella ;. B cell memory; Immunoglobulin lgA; Mucosal immunity Abstract We studied the induction of antigen-specific lgA memory B cells (BM) in

  9. Suppression of large edge localized modes in high confinement DIII-D plasmas with a stochastic magnetic boundary

    Energy Technology Data Exchange (ETDEWEB)

    Evans, T.E. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States)]. E-mail: evans@fusion.gat.com; Moyer, R.A. [University of California at San Diego, La Jolla, CA 92093-0417 (United States); Watkins, J.G. [Sandia National Laboratories, Albuquerque, NM 87185-1129 (United States); Thomas, P.R. [Association Euratom-CEA, CEA Cadarache, F-13108, St. Paul-lez-Durance (France); Osborne, T.H. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Boedo, J.A. [University of California at San Diego, La Jolla, CA 92093-0417 (United States); Fenstermacher, M.E. [Lawrence Livermore National Laborabory, Livermore, CA 94550 (United States); Finken, K.H. [Forschungszentrum Juelich, Institute for Plasma Physics, D52425 Juelich (Germany); Groebner, R.J. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Groth, M. [Lawrence Livermore National Laborabory, Livermore, CA 94550 (United States); Harris, J. [Australian National University, Canberra (Australia); Jackson, G.L. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Haye, R.J. La [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Lasnier, C.J. [Lawrence Livermore National Laborabory, Livermore, CA 94550 (United States); Schaffer, M.J. [General Atomics, P.O. Box 85608, San Diego, CA 92186-5608 (United States); Wang, G. [University of California, Los Angeles, California (United States); Zeng, L. [University of California, Los Angeles, California (United States)

    2005-03-01

    Large 70 Hz Type-I edge localized modes (ELMs) are converted into small 130 Hz oscillations using edge resonant magnetic perturbations (RMPs) from a coil with currents 0.4% I {sub p} in double null DIII-D plasmas. When the RMP is properly phased with respect to the background field errors, all but a few isolated ELM-like events are suppressed. The impulsive pedestal energy loss {delta}E {sub ELM}/{delta}t {sup 1/2} to the scrape-of layer is reduced a factor of 20 relative to the Type-I ELMs and the core confinement is unaffected by the perturbation field. Significant changes in the properties of the ELMs are also observed when edge RMPs are applied to lower single null plasmas but the nature of these changes are much more complex. Both lower single null and double null plasmas are being studied to determine how ELM control techniques based on the application of edge RMPs can be expected to scale to future devices such as ITER.

  10. Semi-allogeneic dendritic cells can induce antigen-specific T-cell activation, which is not enhanced by concurrent alloreactivity.

    Science.gov (United States)

    Wells, James W; Cowled, Chris J; Darling, David; Guinn, Barbara-Ann; Farzaneh, Farzin; Noble, Alistair; Galea-Lauri, Joanna

    2007-12-01

    Alloreactive T-cell responses are known to result in the production of large amounts of proinflammatory cytokines capable of activating and maturing dendritic cells (DC). However, it is unclear whether these allogeneic responses could also act as an adjuvant for concurrent antigen-specific responses. To examine effects of simultaneous alloreactive and antigen-specific T-cell responses induced by semi-allogeneic DC. Semi-allogeneic DC were generated from the F(1) progeny of inbred strains of mice (C57BL/6 and C3H, or C57BL/6 and DBA). We directly primed antigen-specific CD8(+) and CD4(+) T-cells from OT-I and OT-II mice, respectively, in the absence of allogeneic responses, in vitro, and in the presence or absence of alloreactivity in vivo. In vitro, semi-allogeneic DC cross-presented ovalbumin (OVA) to naïve CD8(+) OT-I transgenic T-cells, primed naïve CD4(+) OT-II transgenic T-cells and could stimulate strong alloreactive T-cell proliferation in a primary mixed lymphocyte reaction (MLR). In vivo, semi-allogeneic DC migrated efficiently to regional lymph nodes but did not survive there as long as autologous DC. In addition, they were not able to induce cytotoxic T-lymphocyte (CTL) activity to a target peptide, and only weakly stimulated adoptively transferred OT-II cells. The CD4(+) response was unchanged in allo-tolerized mice, indicating that alloreactive T-cell responses could not provide help for concurrently activated antigen-specific responses. In an EL4 tumour-treatment model, vaccination with semi-allogeneic DC/EL4 fusion hybrids, but not allogeneic DC/EL4 hybrids, significantly increased mouse survival. Expression of self-Major histocompatibility complex (MHC) by semi-allogeneic DC can cause the induction of antigen-specific immunity, however, concurrently activated allogeneic bystander responses do not provide helper or adjuvant effects.

  11. The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

    Science.gov (United States)

    Ponti, Donatella; Bellenchi, Gian Carlo; Puca, Rosa; Bastianelli, Daniela; Maroder, Marella; Ragona, Giuseppe; Roussel, Pascal; Thiry, Marc; Mercola, Dan; Calogero, Antonella

    2014-01-01

    EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

  12. The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

    Directory of Open Access Journals (Sweden)

    Donatella Ponti

    Full Text Available EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

  13. The ALFALFA H I mass function: a dichotomy in the low-mass slope and a locally suppressed `knee' mass

    Science.gov (United States)

    Jones, Michael G.; Haynes, Martha P.; Giovanelli, Riccardo; Moorman, Crystal

    2018-06-01

    We present the most precise measurement of the z = 0 H I mass function (HIMF) to date based on the final catalogue of the ALFALFA (Arecibo Legacy Fast ALFA) blind H I survey of the nearby Universe. The Schechter function fit has a `knee' mass log (M_{*} h2_{70}/M_{⊙}) = 9.94 ± 0.01 ± 0.05, a low-mass slope parameter α = -1.25 ± 0.02 ± 0.1, and a normalization φ _{*} = (4.5 ± 0.2 ± 0.8) × 10^{-3} h3_{70} Mpc^{-3 dex^{-1}}, with both random and systematic uncertainties as quoted. Together these give an estimate of the H I content of the z = 0 Universe as Ω _{H I} = (3.9 ± 0.1 ± 0.6) × 10^{-4} h^{-1}_{70} (corrected for H I self-absorption). Our analysis of the uncertainties indicates that the `knee' mass is a cosmologically fair measurement of the z = 0 value, with its largest uncertainty originating from the absolute flux calibration, but that the low-mass slope is only representative of the local Universe. We also explore large-scale trends in α and M* across the ALFALFA volume. Unlike with the 40 per cent sample, there is now sufficient coverage in both of the survey fields to make an independent determination of the HIMF in each. We find a large discrepancy in the low-mass slope (Δα = 0.14 ± 0.03) between the two regions, and argue that this is likely caused by the presence of a deep void in one field and the Virgo cluster in the other. Furthermore, we find that the value of the `knee' mass within the Local Volume appears to be suppressed by 0.18 ± 0.04 dex compared to the global ALFALFA value, which explains the lower value measured by the shallower H I Parkes All Sky Survey (HIPASS). We discuss possible explanations and interpretations of these results and how they can be expanded on with future surveys.

  14. Detection of Amide and Aromatic Proton Resonances of Human Brain Metabolites Using Localized Correlated Spectroscopy Combined with Two Different Water Suppression Schemes

    Directory of Open Access Journals (Sweden)

    Rajakumar Nagarajan

    2010-01-01

    Full Text Available The purpose of the study was to demonstrate the J-coupling connectivity network between the amide, aliphatic, and aromatic proton resonances of metabolites in human brain using two-dimensional (2D localized correlated spectroscopy (L-COSY. Two different global water suppression techniques were combined with L-COSY, one before and another after localizing the volume of interest (VOI. Phantom solutions containing several cerebral metabolites at physiological concentrations were evaluated initially for sequence optimization. Nine healthy volunteers were scanned using a 3T whole body MRI scanner. The VOI for 2D L-COSY was placed in the right occipital white/gray matter region. The 2D cross and diagonal peak volumes were measured for several metabolites such as N-acetyl aspartate (NAA, creatine (Cr, free choline (Ch, glutamate/glutamine (Glx, aspartate (Asp, myo-inositol (mI, GABA, glutathione (GSH, phosphocholine (PCh, phosphoethanolamine (PE, tyrosine (Tyr, lactate (Lac, macromolecules (MM and homocarnosine (Car. Using the pre-water suppression technique with L-COSY, the above mentioned metabolites were clearly identifiable and the relative ratios of metabolites were calculated. In addition to detecting multitude of aliphatic resonances in the high field region, we have demonstrated that the amide and aromatic resonances can also be detected using 2D L-COSY by pre water suppression more reliably than the post-water suppression.

  15. Generation of Recombinant Monoclonal Antibodies from Immunised Mice and Rabbits via Flow Cytometry and Sorting of Antigen-Specific IgG+ Memory B Cells.

    Directory of Open Access Journals (Sweden)

    Dale O Starkie

    Full Text Available Single B cell screening strategies, which avoid both hybridoma fusion and combinatorial display, have emerged as important technologies for efficiently sampling the natural antibody repertoire of immunized animals and humans. Having access to a range of methods to interrogate different B cell subsets provides an attractive option to ensure large and diverse panels of high quality antibody are produced. The generation of multiple antibodies and having the ability to find rare B cell clones producing IgG with unique and desirable characteristics facilitates the identification of fit-for-purpose molecules that can be developed into therapeutic agents or research reagents. Here, we describe a multi-parameter flow cytometry single-cell sorting technique for the generation of antigen-specific recombinant monoclonal antibodies from single IgG+ memory B cells. Both mouse splenocytes and rabbit PBMC from immunised animals were used as a source of B cells. Reagents staining both B cells and other unwanted cell types enabled efficient identification of class-switched IgG+ memory B cells. Concurrent staining with antigen labelled separately with two spectrally-distinct fluorophores enabled antigen-specific B cells to be identified, i.e. those which bind to both antigen conjugates (double-positive. These cells were then typically sorted at one cell per well using FACS directly into a 96-well plate containing reverse transcriptase reaction mix. Following production of cDNA, PCR was performed to amplify cognate heavy and light chain variable region genes and generate transcriptionally-active PCR (TAP fragments. These linear expression cassettes were then used directly in a mammalian cell transfection to generate recombinant antibody for further testing. We were able to successfully generate antigen-specific recombinant antibodies from both the rabbit and mouse IgG+ memory B cell subset within one week. This included the generation of an anti-TNFR2 blocking

  16. Accelerated production of antigen-specific T-cells for pre-clinical and clinical applications using Gas-permeable Rapid Expansion cultureware (G-Rex)

    Science.gov (United States)

    Vera, Juan F.; Brenner, Lara J.; Gerdemann, Ulrike; Ngo, Minhtran C.; Sili, Uluhan; Liu, Hao; Wilson, John; Dotti, Gianpietro; Heslop, Helen E.; Leen, Ann M.; Rooney, Cliona M.

    2009-01-01

    The clinical manufacture of antigen-specific cytotoxic T lymphocytes (CTL) for adoptive immunotherapy is limited by the complexity and time required to produce large numbers with the desired function and specificity. The culture conditions required are rigorous, and in some cases only achieved in 2cm2 wells in which cell growth is limited by gas exchange, nutrients and waste accumulation. Bioreactors developed to overcome these issues tend to be complex, expensive and not always conducive to CTL growth. We observed that antigen-specific CTL undergo seven to ten divisions post-stimulation. However the expected CTL numbers were achieved only in the first week of culture. By recreating the culture conditions present during this first week - low frequency of antigen-specific T-cells and high frequency of feeder cells - we were able to increase CTL expansion to expected levels which could be sustained for several weeks without affecting phenotype or function. However, the number of 24-well plates needed was excessive and cultures required frequent media changes, increasing complexity and manufacturing costs. Therefore, we evaluated novel gas-permeable culture devices (G-Rex) with a silicone membrane at the base allowing gas exchange to occur uninhibited by depth of medium above. This system effectively supports the expansion of CTL and actually increases output by up to 20-fold while decreasing required technician time. Importantly, this amplified cell expansion is not due to more cell divisions but to reduced cell death. This bioprocess optimization increased T-cell output while decreasing the complexity and cost of CTL manufacture, making cell therapy more accessible. PMID:20445351

  17. Enumeration of antigen-specific CD8+ T lymphocytes by single-platform, HLA tetramer-based flow cytometry: a European multicenter evaluation.

    Science.gov (United States)

    Heijnen, Ingmar A F M; Barnett, David; Arroz, Maria J; Barry, Simon M; Bonneville, Marc; Brando, Bruno; D'hautcourt, Jean-Luc; Kern, Florian; Tötterman, Thomas H; Marijt, Erik W A; Bossy, David; Preijers, Frank W M B; Rothe, Gregor; Gratama, Jan W

    2004-11-01

    HLA class I peptide tetramers represent powerful diagnostic tools for detection and monitoring of antigen-specific CD8(+) T cells. The impetus for the current multicenter study is the critical need to standardize tetramer flow cytometry if it is to be implemented as a routine diagnostic assay. Hence, the European Working Group on Clinical Cell Analysis set out to develop and evaluate a single-platform tetramer-based method that used cytomegalovirus (CMV) as the antigenic model. Absolute numbers of CMV-specific CD8(+) T cells were obtained by combining the percentage of tetramer-binding cells with the absolute CD8(+) T-cell count. Six send-outs of stabilized blood from healthy individuals or CMV-carrying donors with CMV-specific CD8(+) T-cell counts of 3 to 10 cells/microl were distributed to 7 to 16 clinical sites. These sites were requested to enumerate CD8(+) T cells and, in the case of CMV-positive donors, CMV-specific subsets on three separate occasions using the standard method. Between-site coefficients of variation of less than 10% (absolute CD8(+) T-cell counts) and approximately 30% (percentage and absolute numbers of CMV-specific CD8(+) T cells) were achieved. Within-site coefficients of variation were approximately 5% (absolute CD8(+) T-cell counts), approximately 9% (percentage CMV-specific CD8(+) T cells), and approximately 17% (absolute CMV-specific CD8(+) T-cell counts). The degree of variation tended to correlate inversely with the proportion of CMV-specific CD8(+) T-cell subsets. The single-platform MHC tetramer-based method for antigen-specific CD8(+) T-cell counting has been evaluated by a European group of laboratories and can be considered a reproducible assay for routine enumeration of antigen-specific CD8(+) T cells. (c) 2004 Wiley-Liss, Inc.

  18. Diabetes is associated with lower tuberculosis antigen-specific interferon gamma release in Tanzanian tuberculosis patients and non-tuberculosis controls

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, Daniel; Aabye, Martine Grosos; Jensen, Andreas Vestergaard

    2014-01-01

    in diabetes patients and therefore the validity of interferon gamma release assays (IGRA) may be compromised. The aim of the present study was to assess the association between diabetes and Mycobacterium tuberculosis (Mtb) antigen-specific interferon gamma (IFN-γ) release in a TB endemic area among culture......-confirmed TB patients and non-TB controls. Methods: Culture-confirmed pulmonary TB patients (n = 187) and healthy non-TB neighbourhood controls (n = 190) from Mwanza, Tanzania were tested for the presence of circulating T cells recognizing Mtb antigens using an IGRA. The diabetes status of all participants...

  19. Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

    Science.gov (United States)

    Yamamoto, Tsunehisa; Tamaki, Kayoko; Shirakawa, Kohsuke; Ito, Kentaro; Yan, Xiaoxiang; Katsumata, Yoshinori; Anzai, Atsushi; Matsuhashi, Tomohiro; Endo, Jin; Inaba, Takaaki; Tsubota, Kazuo; Sano, Motoaki; Fukuda, Keiichi; Shinmura, Ken

    2016-04-15

    Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol 308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting

  20. Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment. Project 3 - Development of Antigen-Specific Cancer Vaccines for the Control of Ovarian Cancer

    National Research Council Canada - National Science Library

    Kurman, Robert

    2003-01-01

    The purpose of this study is to test whether the greater extent of intracellular spreading of encoded antigen will generate a higher degree of antigen-specific immunity and ant-tumor effects in vaccinated mice...

  1. Antigen-specific secretion of IFNγ and CXCL10 in whole blood assay detects Mycobacterium leprae infection but does not discriminate asymptomatic infection from symptomatic leprosy.

    Science.gov (United States)

    Hungria, Emerith Mayra; Freitas, Aline Araújo; Pontes, Maria Araci Andrade; Gonçalves, Heitor Sá; Sousa, Ana Lúcia Osório Maroccolo; Costa, Maurício Barcelos; Castilho, Mirian Lane Oliveira Rodrigues; Duthie, Malcolm S; Stefani, Mariane Martins Araújo

    2017-04-01

    To advance toward a whole blood assay (WBA)-based test capable of facilitating the diagnosis of paucibacillary (PB) leprosy, we evaluated a prototype in-tube WBA using combinations of Mycobacterium leprae antigens. Blood was collected from newly diagnosed untreated PB (n=38), multibacillary (MB) (n=30), healthy household contacts (HHC) of MB (n=27), and endemic controls (n=61) residing in Goiânia and Fortaleza, Brazil. Blood was incubated with M. leprae cell sonicate, recombinant proteins (46f+LID-1; ML0276+LID-1), or controls (phosphate-buffered saline, phytohemagglutinin, M. tuberculosis purified protein derivative). Antigen-specific IFNγ production was observed in 71-84% and 55% of PB and HHC, respectively. Antigen-specific CXCL10 levels were similarly assessed to determine if, unlike IFNγ, CXCL10 could differentiate PB from HHC with repeated exposure/asymptomatic M. leprae infection. The CXCL10 levels induced in response to M. leprae antigens could not, however, differentiate PB from HHC. Despite these limitations, the WBAs reported here still represent important tools for assessing M. leprae infection rates and evaluating the impact of control measures. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Oral dendritic cells mediate antigen-specific tolerance by stimulating TH1 and regulatory CD4+ T cells.

    Science.gov (United States)

    Mascarell, Laurent; Lombardi, Vincent; Louise, Anne; Saint-Lu, Nathalie; Chabre, Henri; Moussu, Hélène; Betbeder, Didier; Balazuc, Anne-Marie; Van Overtvelt, Laurence; Moingeon, Philippe

    2008-09-01

    A detailed characterization of oral antigen-presenting cells is critical to improve second-generation sublingual allergy vaccines. To characterize oral dendritic cells (DCs) within lingual and buccal tissues from BALB/c mice with respect to their surface phenotype, distribution, and capacity to polarize CD4(+) T-cell responses. In situ analysis of oral DCs was performed by immunohistology. Purified DCs were tested in vitro for their capacity to capture, process, and present the ovalbumin antigen to naive CD4(+) T cells. In vivo priming of ovalbumin-specific T cells adoptively transferred to BALB/c mice was analyzed by cytofluorometry in cervical lymph nodes after sublingual administration of mucoadhesive ovalbumin. Three subsets of oral DCs with a distinct tissue distribution were identified: (1) a minor subset of CD207(+) Langerhans cells located in the mucosa itself, (2) a major subpopulation of CD11b(+)CD11c(-) and CD11b(+)CD11c(+) myeloid DCs at the mucosal/submucosal interface, and (3) B220(+)120G8(+) plasmacytoid DCs found in submucosal tissues. Purified myeloid and plasmacytoid oral DCs capture and process the antigen efficiently and are programmed to elicit IFN-gamma and/or IL-10 production together with a suppressive function in naive CD4(+) T cells. Targeting the ovalbumin antigen to oral DCs in vivo by using mucoadhesive particles establishes tolerance in the absence of cell depletion through the stimulation of IFN-gamma and IL-10-producing CD4(+) regulatory T cells in cervical lymph nodes. The oral immune system is composed of various subsets of tolerogenic DCs organized in a compartmentalized manner and programmed to induce T(H)1/regulatory T-cell responses.

  3. MicroRNA-29b modulates innate and antigen-specific immune responses in mouse models of autoimmunity.

    Directory of Open Access Journals (Sweden)

    Apolline Salama

    Full Text Available In addition to important regulatory roles in gene expression through RNA interference, it has recently been shown that microRNAs display immune stimulatory effects through direct interaction with receptors of innate immunity of the Toll-like receptor family, aggravating neuronal damage and tumour growth. Yet no evidence exists on consequences of microRNA immune stimulatory actions in the context of an autoimmune disease. Using microRNA analogues, we here show that pancreatic beta cell-derived microRNA sequences induce pro-inflammatory (TNFa, IFNa, IL-12, IL-6 or suppressive (IL-10 cytokine secretion by primary mouse dendritic cells in a sequence-dependent manner. For miR-29b, immune stimulation in RAW264.7 macrophages involved the endosomal Toll-like receptor-7, independently of the canonical RNA interference pathway. In vivo, the systemic delivery of miR-29b activates CD11b+B220- myeloid and CD11b-B220+ plasmacytoid dendritic cells and induces IFNa, TNFa and IL-6 production in the serum of recipient mice. Strikingly, in a murine model of adoptive transfer of autoimmune diabetes, miR-29b reduces the cytolytic activity of transferred effector CD8+ T-cells, insulitis and disease incidence in a single standalone intervention. Endogenous miR-29b, spontaneously released from beta-cells within exosomes, stimulates TNFa secretion from spleen cells isolated from diabetes-prone NOD mice in vitro. Hence, microRNA sequences modulate innate and ongoing adaptive immune responses raising the question of their potential role in the breakdown of tolerance and opening up new applications for microRNA-based immune therapy.

  4. A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sakamoto Atsuhiro

    2011-01-01

    Full Text Available Abstract Background Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown. Results Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF, which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain. Conclusions Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

  5. Evaluation of Antigen-Specific IgM and IgG Production during an In Vitro Peripheral Blood Mononuclear Cell Culture Assay

    Directory of Open Access Journals (Sweden)

    Yoshiko Matsuda

    2017-07-01

    Full Text Available The recent attention given to diseases associated with memory B-cell (mBC-produced antibodies (Abs suggests the need for a similar in vitro assay to evaluate the functions of mBCs. Here, we cultured peripheral blood mononuclear cells (PBMCs with the intent to collect mBC-derived Abs in vitro and maintain their cell–cell contact-dependent interactions with helper T-cells. PBMCs were cultured with interleukin (IL-21, CpG-oligodeoxynucleotides (ODN, phorbol myristate acetate (PMA, and phytohemagglutinin/leucoagglutinin (PHA-L in 24-well flat-bottom plates (5 × 105 cells/well. A culture supernatant analysis of PBMCs from healthy donors (n = 10 indicated that antigen-specific IgM Ab levels in a PBMC culture supernatant might be better able to demonstrate the antigen sensitization status in a smaller peripheral blood sample, compared to IgG because Epstein–Barr virus-specific IgM mBCs circulate peripherally at a significantly higher frequency once antiviral humoral immunity has stabilized. Thus, our in vitro assay demonstrated the potential significance of antigen-specific IgM Ab production in the culture supernatants. Furthermore, an analysis of cultured PBMCs from allograft kidney recipients (n = 16 sensitized with de novo donor-specific human leukocyte antigen (HLA-specific Abs (DSAs showed that IgM-type HLA-specific Abs were detected mainly from the culture supernatants from PBMCs of patients with stable graft function, whereas IgG isotype HLA Abs were detectable only from patients with biopsy-proven antibody-mediated rejection. In other words, these IgG isotype Abs also represented an activated humoral immune response in vivo. Additionally, IgM- and IgG-expressing mBCs from healthy donors (n = 5 were cultured with IL-21, CpG-ODN, and a supernatant produced by stimulating CD19+ B-cell-depleted PBMCs with PHA-L and PMA in 24-well flat-bottom plates (1 × 105 cells/well, and the resulting in vitro analysis provided some

  6. Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice

    International Nuclear Information System (INIS)

    Bestak, Rosa; Halliday, G.M.

    1996-01-01

    It has previously been demonstrated that chronic low-dose solar-simulated UV radiation could induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. In this study, we have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/HeJ mice. Irradiation with UVA+B significantly suppressed the local and systemic primary contact hypersensitivity (CHS) response to the hapten 2,4,6-trinitrochlorobenzene. Furthermore, UVA+B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) densities in chronically UV-irradiated mice. Ultraviolet A irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with both UVA+B and UVA radiation also induced an impaired secondary CHS response, and this tolerance was transferable with spleen cells. (Author)

  7. Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects Kupffer cell-restricted antigen presentation to antigen-specific CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Lynette Beattie

    2010-03-01

    Full Text Available Kupffer cells (KCs represent the major phagocytic population within the liver and provide an intracellular niche for the survival of a number of important human pathogens. Although KCs have been extensively studied in vitro, little is known of their in vivo response to infection and their capacity to directly interact with antigen-specific CD8(+ T cells. Here, using a combination of approaches including whole mount and thin section confocal microscopy, adoptive cell transfer and intra-vital 2-photon microscopy, we demonstrate that KCs represent the only detectable population of mononuclear phagocytes within granulomas induced by Leishmania donovani infection that are capable of presenting parasite-derived peptide to effector CD8(+ T cells. This restriction of antigen presentation to KCs within the Leishmania granuloma has important implications for the identification of new candidate vaccine antigens and for the design of novel immuno-therapeutic interventions.

  8. Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity

    International Nuclear Information System (INIS)

    Golding, H.; Munitz, T.I.; Singer, A.

    1985-01-01

    The goals of the present study were: (a) to generate antigen-specific L3T4+ cytolytic T lymphocytes (CTL), (b) to determine their major histocompatibility complex (MHC) restriction specificity, and (c) to assess the influence of thymic MHC determinants on their self specificity. The authors found that L3T4+ CTL specific for either trinitrophenyl (TNP)-modified self determinants or minor histocompatibility antigens could be generated from Lyt-2- responder T cells provided that the response cultures were supplemented with supernatants rich in helper factors. Such antigen-specific L3T4+ CTL were Ia-restricted by the criteria that they lysed only Ia+ target cells and that their lysis of Ia+ target cells was specifically inhibited by anti-Ia monoclonal antibodies. The relative frequency of L3T4+ pCTL was found to be only 5-10% of the total anti-TNP pCTL present in the spleens of normal mice. Finally, the authors utilized radiation bone marrow chimeras to assess the influence of the thymic haplotype on the self-Ia specificity of L3T4+ CTL. Both bulk culture and limiting dilution experiments revealed that the self-Ia specificity of L3T4+ anti-TNP CTL from F1----parent and A----B allogeneic chimeras was not markedly skewed toward the haplotype of the chimeric thymus. These results contrast with those obtained previously for L3T4+ anti-TNP Th cells and demonstrate that in the radiation bone marrow chimera model of T cell differentiation, the self specificity of Th cells but not pCTL is markedly influenced by the haplotype of the chimeric thymus

  9. Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies

    Directory of Open Access Journals (Sweden)

    Katherine E. Harris

    2018-04-01

    Full Text Available We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1. This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.

  10. Formulation of the bivalent prostate cancer vaccine with surgifoam elicits antigen-specific effector T cells in PSA-transgenic mice.

    Science.gov (United States)

    Karan, Dev

    2017-10-13

    We previously developed and characterized an adenoviral-based prostate cancer vaccine for simultaneous targeting of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA). We also demonstrated that immunization of mice with the bivalent vaccine (Ad 5 -PSA+PSCA) inhibited the growth of established prostate tumors. However, there are multiple challenges hindering the success of immunological therapies in the clinic. One of the prime concerns has been to overcome the immunological tolerance and maintenance of long-term effector T cells. In this study, we further characterized the use of the bivalent vaccine (Ad 5 -PSA+PSCA) in a transgenic mouse model expressing human PSA in the mouse prostate. We demonstrated the expression of PSA analyzed at the mRNA level (by RT-PCR) and protein level (by immunohistochemistry) in the prostate lobes harvested from the PSA-transgenic (PSA-Tg) mice. We established that the administration of the bivalent vaccine in surgifoam to the PSA-Tg mice induces strong PSA-specific effector CD8 + T cells as measured by IFN-γ secretion and in vitro cytotoxic T-cell assay. Furthermore, the use of surgifoam with Ad 5 -PSA+PSCA vaccine allows multiple boosting vaccinations with a significant increase in antigen-specific CD8 + T cells. These observations suggest that the formulation of the bivalent prostate cancer vaccine (Ad 5 -PSA+PSCA) with surgifoam bypasses the neutralizing antibody response, thus allowing multiple boosting. This formulation is also helpful for inducing an antigen-specific immune response in the presence of self-antigen, and maintains long-term effector CD8 + T cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.

    Science.gov (United States)

    Xue, Qiong; Bettini, Emily; Paczkowski, Patrick; Ng, Colin; Kaiser, Alaina; McConnell, Timothy; Kodrasi, Olja; Quigley, Máire F; Heath, James; Fan, Rong; Mackay, Sean; Dudley, Mark E; Kassim, Sadik H; Zhou, Jing

    2017-11-21

    It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high

  12. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route.

    Science.gov (United States)

    Carey, John B; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V S; Draper, Simon J; Moore, Anne C

    2014-08-21

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP1₄₂, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP1₄₂ also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP1₄₂ using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

  13. Antigen-specific T8+ human clone of cells with a nonspecific augmenting function on the T4 cell-B cell helper interaction

    International Nuclear Information System (INIS)

    Brines, R.D.; Sia, D.Y.; Lehner, T.

    1987-01-01

    The authors isolated a T8 + T3 + Ia + clone of cells from the peripheral blood mononuclear cells of a healthy subject. The clone was expanded and maintained with autologous feed cells, interleukin 2, and a streptococcal antigen. The T8 + clone of cells responded specifically to the streptococcal antigen, in the absence of accessory cells,and released a soluble factor. Both the cloned cells and the corresponding soluble factor expressed augmenting helper but not suppressor activity. The augmenting helper activity for B cell antibody synthesis was demonstrable only in the presence of autologous T 4 cells. Radioimmunoassay was used to measure antibodies. Although stimulation of the T8 + cloned cells was antigen-specific, the resulting soluble factor elicited nonspecific antibody synthesis in the presence of T4 and B cells. The T8 + cloned cell-derived factor was adsorbed by B cells but not by T4 cells. Preliminary studies suggest that the factor has the properties of a B cell growth factor. They suggest that the T8 + population consists of functionally heterogeneous cell subsets, some that have suppressor function and others that augment the T4 + helper-inducer activity in B cell antibody synthesis

  14. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

    Science.gov (United States)

    Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

    2014-01-01

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

  15. Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

    Directory of Open Access Journals (Sweden)

    Michael C. Gong

    1999-06-01

    Full Text Available The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

  16. Suppression of spiral wave and turbulence by using amplitude restriction of variable in a local square area

    International Nuclear Information System (INIS)

    Ma Jun; Jia Ya; Yi Ming; Tang Jun; Xia Yafeng

    2009-01-01

    In this paper, a new scheme is proposed to eliminate the useless spiral wave and turbulence in the excitable media. The activator amplitudes of few sites in the media are sampled and restricted within the appropriate thresholds. At first, the local control is imposed on the center of the media, and then the local control is introduced into the left border in the media. The numerical simulation results confirm that the whole media can reach homogeneous within few time units even if the spatiotemporal noise is imposed on the whole media. To check the model independence of this scheme, the scheme is used to remove the spiral wave in the Fitzhugh-Nagumo model firstly. In our numerical simulation, the whole system is discretized into 400 x 400 sites. Then the scheme is used to eliminate the stable rotating spiral wave, meandering spiral and spiral turbulence in the modified Fitzhugh-Nagumo model, respectively. Finally, this scheme is used to remove the stable rotating spiral wave in the Belousov-Zhabotinsky (BZ) reaction. All the results just confirm its effectiveness to eliminate the spiral wave and turbulence. The criterion for thresholds selection is also discussed in the end of this paper.

  17. A novel insulinotropic mechanism of whole grain-derived γ-oryzanol via the suppression of local dopamine D2 receptor signalling in mouse islet.

    Science.gov (United States)

    Kozuka, Chisayo; Sunagawa, Sumito; Ueda, Rei; Higa, Moritake; Ohshiro, Yuzuru; Tanaka, Hideaki; Shimizu-Okabe, Chigusa; Takayama, Chitoshi; Matsushita, Masayuki; Tsutsui, Masato; Ishiuchi, Shogo; Nakata, Masanori; Yada, Toshihiko; Miyazaki, Jun-Ichi; Oyadomari, Seiichi; Shimabukuro, Michio; Masuzaki, Hiroaki

    2015-07-03

    γ-Oryzanol, derived from unrefined rice, attenuated the preference for dietary fat in mice, by decreasing hypothalamic endoplasmic reticulum stress. However, no peripheral mechanisms, whereby γ-oryzanol could ameliorate glucose dyshomeostasis were explored. Dopamine D 2 receptor signalling locally attenuates insulin secretion in pancreatic islets, presumably via decreased levels of intracellular cAMP. We therefore hypothesized that γ-oryzanol would improve high-fat diet (HFD)-induced dysfunction of islets through the suppression of local D 2 receptor signalling. Glucose metabolism and regulation of molecules involved in D 2 receptor signalling in pancreatic islets were investigated in male C57BL/6J mice, fed HFD and treated with γ-oryzanol . In isolated murine islets and the beta cell line, MIN6 , the effects of γ-oryzanol on glucose-stimulated insulin secretion (GSIS) was analysed using siRNA for D 2 receptors and a variety of compounds which alter D 2 receptor signalling. In islets, γ-oryzanol enhanced GSIS via the activation of the cAMP/PKA pathway. Expression of molecules involved in D 2 receptor signalling was increased in islets from HFD-fed mice, which were reciprocally decreased by γ-oryzanol. Experiments with siRNA for D 2 receptors and D 2 receptor ligands in vitro suggest that γ-oryzanol suppressed D 2 receptor signalling and augmented GSIS. γ-Oryzanol exhibited unique anti-diabetic properties. The unexpected effects of γ-oryzanol on D 2 receptor signalling in islets may provide a novel; natural food-based, approach to anti-diabetic therapy. © 2015 The British Pharmacological Society.

  18. Near-infrared labeled, ovalbumin loaded polymeric nanoparticles based on a hydrophilic polyester as model vaccine : In vivo tracking and evaluation of antigen-specific CD8+ T cell immune response

    NARCIS (Netherlands)

    Rahimian, Sima; Kleinovink, Jan Willem; Fransen, Marieke F.; Mezzanotte, Laura; Gold, Henrik; Wisse, Patrick; Overkleeft, Hermen; Amidi, Maryam; Jiskoot, Wim; Lo¨wik, Clemens W.; Ossendorp, Ferry; Hennink, Wim E.

    2015-01-01

    Particulate antigen delivery systems aimed at the induction of antigen-specific T cells form a promising approach in immunotherapy to replace pharmacokinetically unfavorable soluble antigen formulations. In this study, we developed a delivery system using the model protein antigen ovalbumin (OVA)

  19. Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis▿ †

    Science.gov (United States)

    Feske, Marsha; Nudelman, Rodolfo J.; Medina, Miguel; Lew, Justin; Singh, Manisha; Couturier, Jacob; Graviss, Edward A.; Lewis, Dorothy E.

    2008-01-01

    Children and immunocompromised adults are at an increased risk of tuberculosis (TB), but diagnosis is more challenging. Recently developed gamma interferon (IFN-γ) release assays provide increased sensitivity and specificity for diagnosis of latent TB, but their use is not FDA approved in immunocompromised or pediatric populations. Both populations have reduced numbers of T cells, which are major producers of IFN-γ. Interleukin 7 (IL-7), a survival cytokine, stabilizes IFN-γ message and increases protein production. IL-7 was added to antigen-stimulated lymphocytes to improve IFN-γ responses as measured by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot (ELISPOT) assay. Antigens used were tetanus toxoid (n = 10), p24 (from human immunodeficiency virus [HIV], n = 9), and TB peptides (n = 15). Keyhole limpet hemocyanin was used as a negative control, and phytohemagglutinin was the positive control. IL-7 improved antigen-specific responses to all antigens tested including tetanus toxoid, HIV type 1 p24, and TB peptides (ESAT-6 and CFP-10) with up to a 14-fold increase (mean = 3.8), as measured by ELISA. Increased IFN-γ responses from controls, HIV-positive patients, and TB patients were statistically significant, with P values of <0.05, 0.01, and 0.05, respectively. ELISPOT assay results confirmed ELISA findings (P values of <0.01, 0.02, and 0.03, respectively), with a strong correlation between the two tests (R2 = 0.82 to 0.99). Based on average background levels, IL-7 increased detection of IFN-γ by 39% compared to the level with antigen alone. Increased production of IFN-γ induced by IL-7 improves sensitivity of ELISA and ELISPOT assays for all antigens tested. Further enhancement of IFN-γ-based assays might improve TB diagnosis in those populations at highest risk for TB. PMID:18753334

  20. Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets.

    Science.gov (United States)

    Bassaganya-Riera, Josep; Guri, Amir J; Noble, Alexis M; Reynolds, Kathryn A; King, Jennifer; Wood, Cynthia M; Ashby, Michael; Rai, Deshanie; Hontecillas, Raquel

    2007-03-01

    Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. The objective of this study was to investigate the ability of AA- and DHA(AA/DHA)-enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed-type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. The influenza virus-specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.

  1. Tracking in vivo migration and distribution of antigen-specific cytotoxic T lymphocytes by 5,6-carboxyfluorescein diacetate succinimidyl ester staining during cancer immunotherapy.

    Science.gov (United States)

    Xu, Wei-li; Li, Suo-lin; Wen, Ming; Wen, Jun-ye; Han, Jie; Zhang, Hong-zhen; Gao, Fei; Cai, Jian-hui

    2013-08-01

    Killing of targeted tumors during adoptive cell transfer therapy is associated with cytotoxic T lymphocyte (CTL) numbers, immunophenotype, tumor-specificity, and in vivo residence time, migration, and distribution. Therefore, tracing in vivo persistence, migration, and distribution of CTLs is important for cancer immunotherapy. Optimal staining concentration for CTL proliferation was determined by cell counting kit-8 (CCK-8) assay and killing efficiencies of CTLs or carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled melanoma antigen-specific cytotoxic T lymphocytes (CFSE-CTLs) for malignant melanoma cells in vitro were compared. Additionally, CFSE-CTLs were intravenously transfused to mice receiving B16 melanoma, and their residence time, migration, and distribution in vivo were observed by measuring fluorescence intensities of CFSE-CTLs per gram of tissue (%FI/g) in various tissues and analyzing tumor/non-tumor (T/NT) values. Anti-tumor effects of transferred CTLs and correlation between %FI/g and D-value of tumor size were analyzed. Five-micromolar CFSE was optimal for labeling CTLs with minimal cytotoxicity. No significant difference occurred between CTLs and CFSE-CTLs for tumor cell killing (P = 0.849) or interleukin-2 (P = 0.318) and interferon-γ (P = 0.201) levels. Distribution of CTLs in vivo varied with time. A negative correlation between %FI/g in tumors and D-value of tumor sizes by Spearman correlation analysis was observed. CTLs were recruited to and killed tumors from 6 hours to 3 days after cell infusion. CTLs were observed up to three weeks later in the tumor, liver, kidneys, and spleen; this was related to the abundant blood supply or the nature of immune organs. CCK-8 assay is a novel method to select optimal CFSE staining concentrations. Fluorescence intensity of transferred CTLs reflects their killing efficiency of tumors. CFSE fluorescent markers can trace in vivo CTL persistence, migration, and distribution because of its stability

  2. Antigen-Specificity of T Cell Infiltrates in Biopsies With T Cell-Mediated Rejection and BK Polyomavirus Viremia: Analysis by Next Generation Sequencing.

    Science.gov (United States)

    Zeng, G; Huang, Y; Huang, Y; Lyu, Z; Lesniak, D; Randhawa, P

    2016-11-01

    This study interrogates the antigen-specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA-A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell-receptor complementary DNA was performed on peptide-stimulated PBMC and 23 biopsies with T cell-mediated rejection (TCMR) or BKPyVN. Biopsies from patients with BKPyVM or BKVPyVN contained 7.7732 times more alloreactive than virus-reactive clones. Biopsies with TCMR also contained BKPyV-specific clones, presumably a manifestation of heterologous immunity. The mean cumulative T cell clonal frequency was 0.1378 for alloreactive clones and 0.0375 for BKPyV-reactive clones. Samples with BKPyVN and TCMR clustered separately in dendrograms of V-family and J-gene utilization patterns. Dendrograms also revealed that V-gene, J-gene, and D-gene usage patterns were a function of HLA type. In conclusion, biopsies with BKPyVN contain abundant allospecific clones that exceed the number of virus-reactive clones. The T cell component of tissue injury in viral nephropathy appears to be mediated primarily by an "innocent bystander" mechanism in which the principal element is secondary T cell influx triggered by both antiviral and anti-HLA immunity. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

    Science.gov (United States)

    Luo, Wen-Hui; Yang, Ya-Wun

    2016-04-01

    The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

  4. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Directory of Open Access Journals (Sweden)

    Luping Du

    2018-01-01

    Full Text Available Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide (PLGA nanoparticles (NPs with Ulex europaeus agglutinin 1 (UEA-1 and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5] or subunit vaccine ORF5-encoded glycoprotein (GP5 from exposure to the gastrointestinal (GI tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05. Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system.

  5. Targeted Delivery of GP5 Antigen of PRRSV to M Cells Enhances the Antigen-Specific Systemic and Mucosal Immune Responses

    Science.gov (United States)

    Du, Luping; Yu, Zhengyu; Pang, Fengjiao; Xu, Xiangwei; Mao, Aihua; Yuan, Wanzhe; He, Kongwang; Li, Bin

    2018-01-01

    Efficient delivery of antigens through oral immunization is a first and critical step for successful induction of mucosal immunity, which can provide protection against pathogens invading the mucosa. Membranous/microfold cells (M cells) within the mucosa can transcytose internalized antigen without degradation and thus play an important role in initiating antigen-specific mucosal immune responses through inducing secretory IgA production. In this research, we modified poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with Ulex europaeus agglutinin 1 (UEA-1) and successfully prepared an oral vaccine delivery system, UEA-1/PLGA NPs. PLGA NPs were prepared using a standard double emulsion solvent evaporation technique, which can protect the entrapped PRRSV DNA vaccine [pcDNA3.1-SynORF5 (synthetic ORF5)] or subunit vaccine ORF5-encoded glycoprotein (GP5) from exposure to the gastrointestinal (GI) tract and release the plasmids in a controlled manner. With UEA-1 modification, the UEA-1/PLGA NPs can be effectively transported by M-cells. We investigated immune response induced by UEA-1/PLGA-SynORF5 or UEA-1/PLGA-GP5 following inoculation in mice and piglets. Compared with PLGA-SynORF5 or PLGA-GP5 NPs, UEA-1/PLGA-SynORF5, or UEA-1/PLGA-GP5 NPs stimulated significantly increased serum IgG levels and augmented intestinal IgA levels in mice and piglets (P < 0.05). Our findings indicate UEA-1/PLGA NPs can be applied as a promising and universally robust oral vaccine delivery system. PMID:29423381

  6. Suppression of in vitro cell-mediated lympholysis generation by alloactivated lymphocytes. Examination of radioresistant suppressive activity

    International Nuclear Information System (INIS)

    Orosz, C.G.; Ferguson, R.M.

    1986-01-01

    We investigated the radioresistant (1000 rads) suppression of CML generation mediated by alloactivated murine splenocytes. Suppressive cells were generated in MLCs by stimulation of (A X 6R)F1 splenocytes with irradiated C57BL/10 splenocytes. Suppressive cells could lyse targets bearing H-2b alloantigens, but would not lyse parental B10.T(6R) or B10.A targets. Suppressive activity was detected by including the alloactivated (A X 6R)F1 cells in B10.T(6R) anti-B10.A(1R) MLCs. Relative to the suppressive (A X 6R)F1 cells, the B10.A(1R) lymphocytes display both parental and suppressor-inducing alloantigens. In the absence of a suppressive population, B10.A(1R) stimulators cause B10.T(6R) splenocytes to generate cytolytic activity specific for both H-2Db (suppressor-inducing) and H-2Kk (suppressor-borne) target determinants. The irradiated, alloactivated (A X 6R)F1 cells decrease the H-2Db-specific CML generated in this system, thus mediating apparent antigen-specific suppression. However, cytolytic activity concomitantly generated in the same culture against the unrelated H-2Kk target determinants is similarly reduced by the (A X 6R)F1 cells. Thus, radioresistant suppression by alloactivated splenocytes is not necessarily antigen-specific. The irradiated (A X 6R)F1 cells would not suppress the generation of H-2Kk-specific CTL in B10.T(6R) anti-B10.A MLCs. Hence, the irradiated (A X 6R)F1 cells can impede CML generation against third-party alloantigens if, and only if, those alloantigens are coexpressed with suppressor-inducing alloantigens on the stimulator cells in suppressed MLCs. Similar results were also obtained using a different histoincompatible lymphocyte combination

  7. Changes in cluster magnetism and suppression of local superconductivity in amorphous FeCrB alloy irradiated by Ar{sup +} ions

    Energy Technology Data Exchange (ETDEWEB)

    Okunev, V.D., E-mail: okunev@mail.fti.ac.donetsk.ua [Donetsk Physiko-Technical Institute, Ukrainian Academy of Sciences, av. Nauki 46, 03028 Kiev (Ukraine); Samoilenko, Z.A. [Donetsk Physiko-Technical Institute, Ukrainian Academy of Sciences, av. Nauki 46, 03028 Kiev (Ukraine); Szymczak, H.; Szewczyk, A.; Szymczak, R.; Lewandowski, S.J.; Aleshkevych, P.; Malinowski, A.; Gierłowski, P.; Więckowski, J. [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland); Wolny-Marszałek, M.; Jeżabek, M. [Institute of Nuclear Physics, Polish Academy of Sciences, Krakow (Poland); Varyukhin, V.N. [Donetsk Physiko-Technical Institute, Ukrainian Academy of Sciences, av. Nauki 46, 03028 Kiev (Ukraine); Antoshina, I.A. [Obninsk State Technical University of Atomic Energy, 249020 Obninsk (Russian Federation)

    2016-02-01

    We show that cluster magnetism in ferromagnetic amorphous Fe{sub 67}Cr{sub 18}B{sub 15} alloy is related to the presence of large, D=150–250 Å, α-(Fe Cr) clusters responsible for basic changes in cluster magnetism, small, D=30–100 Å, α-(Fe, Cr) and Fe{sub 3}B clusters and subcluster atomic α-(Fe, Cr, B) groupings, D=10–20 Å, in disordered intercluster medium. For initial sample and irradiated one (Φ=1.5×10{sup 18} ions/cm{sup 2}) superconductivity exists in the cluster shells of metallic α-(Fe, Cr) phase where ferromagnetism of iron is counterbalanced by antiferromagnetism of chromium. At Φ=3×10{sup 18} ions/cm{sup 2}, the internal stresses intensify and the process of iron and chromium phase separation, favorable for mesoscopic superconductivity, changes for inverse one promoting more homogeneous distribution of iron and chromium in the clusters as well as gigantic (twice as much) increase in density of the samples. As a result, in the cluster shells ferromagnetism is restored leading to the increase in magnetization of the sample and suppression of local superconductivity. For initial samples, the temperature dependence of resistivity ρ(T)~T{sup 2} is determined by the electron scattering on quantum defects. In strongly inhomogeneous samples, after irradiation by fluence Φ=1.5×10{sup 18} ions/cm{sup 2}, the transition to a dependence ρ(T)~T{sup 1/2} is caused by the effects of weak localization. In more homogeneous samples, at Φ=3×10{sup 18} ions/cm{sup 2}, a return to the dependence ρ(T)~T{sup 2} is observed. - Highlights: • The samples at high dose of ion irradiation become more homogeneous. • Gigantic increase in density of the samples (twice as much) is observed. • Ferromagnetism in large Fe–Cr clusters is restored. • Ferromagnetism of Fe–Cr clusters suppresses local superconductivity in them. • The participation of quantum defects in scattering of electrons is returned.

  8. Localization of functional memory B cells at sites of antigen localization and its relationship to local aspects of immunological memory

    International Nuclear Information System (INIS)

    Ponzio, N.M.; Baine, Y.; Thorbecke, G.J.

    1980-01-01

    Experiments are described which have been designed to test whether antigen in a draining lymph node can mediate local accumulation of passively transferred antigen-specific memory B cells, using recipients whose own immune response is inhibited via γ-irradiation or by injection of cyclophosphamide. (Auth.)

  9. NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine.

    Directory of Open Access Journals (Sweden)

    Seth M Pollack

    Full Text Available Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression.We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment.A minority (36% of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic

  10. Strategy for eliciting antigen-specific CD8+ T cell-mediated immune response against a cryptic CTL epitope of merkel cell polyomavirus large T antigen

    Directory of Open Access Journals (Sweden)

    Gomez Bianca P

    2012-10-01

    Full Text Available Abstract Background Merkel cell carcinoma (MCC is a relatively new addition to the expanding category of oncovirus-induced cancers. Although still comparably rare, the number of cases has risen dramatically in recent years. Further complicating this trend is that MCC is an extremely aggressive neoplasm with poor patient prognosis and limited treatment options for advanced disease. The causative agent of MCC has been identified as the merkel cell polyomavirus (MCPyV. The MCPyV-encoded large T (LT antigen is an oncoprotein that is theorized to be essential for virus-mediated tumorigenesis and is therefore, an excellent MCC antigen for the generation of antitumor immune responses. As a foreign antigen, the LT oncoprotein avoids the obstacle of immune tolerance, which normally impedes the development of antitumor immunity. Ergo, it is an excellent target for anti-MCC immunotherapy. Since tumor-specific CD8+ T cells lead to better prognosis for MCC and numerous other cancers, we have generated a DNA vaccine that is capable of eliciting LT-specific CD8+ T cells. The DNA vaccine (pcDNA3-CRT/LT encodes the LT antigen linked to a damage-associated molecular pattern, calreticulin (CRT, as it has been demonstrated that the linkage of CRT to antigens promotes the induction of antigen-specific CD8+ T cells. Results The present study shows that DNA vaccine-induced generation of LT-specific CD8+ T cells is augmented by linking CRT to the LT antigen. This is relevant since the therapeutic effects of the pcDNA3-CRT/LT DNA vaccine is mediated by LT-specific CD8+ T cells. Mice vaccinated with the DNA vaccine produced demonstrably more LT-specific CD8+ T cells. The DNA vaccine was also able to confer LT-specific CD8+ T cell-mediated protective and therapeutic effects to prolong the survival of mice with LT-expressing tumors. In the interest of determining the LT epitope which most MCC-specific CD8+ T cells recognize, we identified the amino acid sequence of the

  11. CD4 Depletion or CD40L Blockade Results in Antigen-Specific Tolerance in a Red Blood Cell Alloimmunization Model

    Directory of Open Access Journals (Sweden)

    Prabitha Natarajan

    2017-08-01

    Full Text Available Approximately 3–10% of human red blood cell (RBC transfusion recipients form alloantibodies to non-self, non-ABO blood group antigens expressed on donor RBCs, with these alloantibodies having the potential to be clinically significant in transfusion and pregnancy settings. However, the majority of transfused individuals never form detectable alloantibodies. Expanding upon observations that children initially transfused with RBCs at a young age are less likely to form alloantibodies throughout their lives, we hypothesized that “non-responders” may not only be ignorant of antigens on RBCs but instead tolerized. We investigated this question in a reductionist murine model, in which transgenic donors express the human glycophorin A (hGPA antigen in an RBC-specific manner. Although wild-type mice treated with poly IC and transfused with hGPA RBCs generated robust anti-hGPA IgG alloantibodies that led to rapid clearance of incompatible RBCs, those transfused in the absence of an adjuvant failed to become alloimmunized. Animals depleted of CD4+ cells or treated with CD40L blockade prior to initial hGPA RBC exposure, in the presence of poly IC, failed to generate detectable anti-hGPA IgG alloantibodies. These non-responders to a primary transfusion remained unable to generate anti-hGPA IgG alloantibodies upon secondary hGPA exposure and did not prematurely clear transfused hGPA RBCs even after their CD4 cells had returned or their CD40L blockade had resolved. This observed tolerance was antigen (hGPA specific, as robust IgG responses to transfused RBCs expressing a third-party antigen occurred in all studied groups. Experiments completed in an RBC alloimmunization model that allowed evaluation of antigen-specific CD4+ T-cells (HOD (hen egg lysozyme, ovalbumin, and human duffyb demonstrated that CD40L blockade prevented the expansion of ovalbumin 323-339 specific T-cells after HOD RBC transfusion and also prevented germinal center formation. Taken

  12. Antigen-specific primed cytotoxic T cells eliminate tumour cells in vivo and prevent tumour development, regardless of the presence of anti-apoptotic mutations conferring drug resistance.

    Science.gov (United States)

    Jaime-Sánchez, Paula; Catalán, Elena; Uranga-Murillo, Iratxe; Aguiló, Nacho; Santiago, Llipsy; M Lanuza, Pilar; de Miguel, Diego; A Arias, Maykel; Pardo, Julián

    2018-05-09

    Cytotoxic CD8 + T (Tc) cells are the main executors of transformed and cancer cells during cancer immunotherapy. The latest clinical results evidence a high efficacy of novel immunotherapy agents that modulate Tc cell activity against bad prognosis cancers. However, it has not been determined yet whether the efficacy of these treatments can be affected by selection of tumoural cells with mutations in the cell death machinery, known to promote drug resistance and cancer recurrence. Here, using a model of prophylactic tumour vaccination based on the LCMV-gp33 antigen and the mouse EL4 T lymphoma, we analysed the molecular mechanism employed by Tc cells to eliminate cancer cells in vivo and the impact of mutations in the apoptotic machinery on tumour development. First of all, we found that Tc cells, and perf and gzmB are required to efficiently eliminate EL4.gp33 cells after LCMV immunisation during short-term assays (1-4 h), and to prevent tumour development in the long term. Furthermore, we show that antigen-pulsed chemoresistant EL4 cells overexpressing Bcl-X L or a dominant negative form of caspase-3 are specifically eliminated from the peritoneum of infected animals, as fast as parental EL4 cells. Notably, antigen-specific Tc cells control the tumour growth of the mutated cells, as efficiently as in the case of parental cells. Altogether, expression of the anti-apoptotic mutations does not confer any advantage for tumour cells neither in the short-term survival nor in long-term tumour formation. Although the mechanism involved in the elimination of the apoptosis-resistant tumour cells is not completely elucidated, neither necroptosis nor pyroptosis seem to be involved. Our results provide the first experimental proof that chemoresistant cancer cells with mutations in the main cell death pathways are efficiently eliminated by Ag-specific Tc cells in vivo during immunotherapy and, thus, provide the molecular basis to treat chemoresistant cancer cells with CD8 Tc

  13. HPV16-E7 expression in squamous epithelium creates a local immune suppressive environment via CCL2- and CCL5- mediated recruitment of mast cells.

    Directory of Open Access Journals (Sweden)

    Anne-Sophie Bergot

    2014-10-01

    Full Text Available Human Papillomavirus (HPV 16 E7 protein promotes the transformation of HPV infected epithelium to malignancy. Here, we use a murine model in which the E7 protein of HPV16 is expressed as a transgene in epithelium to show that mast cells are recruited to the basal layer of E7-expressing epithelium, and that this recruitment is dependent on the epithelial hyperproliferation induced by E7 by inactivating Rb dependent cell cycle regulation. E7 induced epithelial hyperplasia is associated with increased epidermal secretion of CCL2 and CCL5 chemokines, which attract mast cells to the skin. Mast cells in E7 transgenic skin, in contrast to those in non-transgenic skin, exhibit degranulation. Notably, we found that resident mast cells in E7 transgenic skin cause local immune suppression as evidenced by tolerance of E7 transgenic skin grafts when mast cells are present compared to the rejection of mast cell-deficient E7 grafts in otherwise competent hosts. Thus, our findings suggest that mast cells, recruited towards CCL2 and CCL5 expressed by epithelium induced to proliferate by E7, may contribute to an immunosuppressive environment that enables the persistence of HPV E7 protein induced pre-cancerous lesions.

  14. Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial

    International Nuclear Information System (INIS)

    Denham, James W.; Steigler, Allison; Joseph, David; Lamb, David S.; Spry, Nigel A.; Duchesne, Gillian; Atkinson, Chris; Matthews, John; Turner, Sandra; Kenny, Lizbeth; Tai, Keen-Hun; Gogna, Nirdosh Kumar; Gill, Suki; Tan, Hendrick; Kearvell, Rachel; Murray, Judy; Ebert, Martin; Haworth, Annette; Kennedy, Angel; Delahunt, Brett

    2015-01-01

    Background: The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. Methods: We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS ± 18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. Results: Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (p < 0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively. Conclusion: RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration

  15. Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial.

    Science.gov (United States)

    Denham, James W; Steigler, Allison; Joseph, David; Lamb, David S; Spry, Nigel A; Duchesne, Gillian; Atkinson, Chris; Matthews, John; Turner, Sandra; Kenny, Lizbeth; Tai, Keen-Hun; Gogna, Nirdosh Kumar; Gill, Suki; Tan, Hendrick; Kearvell, Rachel; Murray, Judy; Ebert, Martin; Haworth, Annette; Kennedy, Angel; Delahunt, Brett; Oldmeadow, Christopher; Holliday, Elizabeth G; Attia, John

    2015-06-01

    The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear. We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18 months AS±18 months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6 months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5 years for each RDE group. Composite LP declined coherently in the 66, 70 and 74 Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5 years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6 months AS, 18 months AS also significantly reduced LP (pRDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy

    International Nuclear Information System (INIS)

    Pai, Howard Huaihan; Ludgate, Charles; Pickles, Tom; Paltiel, Chuck M.Sc.; Agranovich, Alex; Berthelet, Eric; Duncan, Graeme; Kim-Sing, Charmaine; Kwan, Winkle; Lim, Jan; Liu, Mitchell; Tyldesley, Scott

    2006-01-01

    Purpose: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). Methods and Materials: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. Results: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir + 2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. Conclusions: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival

  17. local

    Directory of Open Access Journals (Sweden)

    Abílio Amiguinho

    2005-01-01

    Full Text Available The process of socio-educational territorialisation in rural contexts is the topic of this text. The theme corresponds to a challenge to address it having as main axis of discussion either the problem of social exclusion or that of local development. The reasons to locate the discussion in this last field of analysis are discussed in the first part of the text. Theoretical and political reasons are there articulated because the question is about projects whose intentions and practices call for the political both in the theoretical debate and in the choices that anticipate intervention. From research conducted for several years, I use contributions that aim at discuss and enlighten how school can be a potential locus of local development. Its identification and recognition as local institution (either because of those that work and live in it or because of those that act in the surrounding context are crucial steps to progressively constitute school as a partner for development. The promotion of the local values and roots, the reconstruction of socio-personal and local identities, the production of sociabilities and the equation and solution of shared problems were the dimensions of a socio-educative intervention, markedly globalising. This scenario, as it is argued, was also, intentionally, one of transformation and of deliberate change of school and of the administration of the educative territoires.

  18. Nasal tolerance induces antigen-specific CD4+CD25- regulatory T cells that can transfer their regulatory capacity to naive CD4+ T cells.

    NARCIS (Netherlands)

    Unger, W.W.J.; Jansen, W.; Wolvers, DA; Halteren, van AG; Kraal, G.; Samsom, J.N.

    2003-01-01

    The mucosal immune system is uniquely adapted to elicit immune responses against pathogens but also to induce tolerogenic responses to harmless antigens. In mice, nasal application of ovalbumin (OVA) leads to suppression of both T(h)1 and T(h)2 responses. This tolerance can be transferred to naive

  19. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Nathella Pavan Kumar

    Full Text Available Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB, their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL and latent tuberculosis (LTB have not been well studied.To identify cytokine responses associated with pulmonary tuberculosis (TB, TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA.PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2; Type 2 (IL-4 and Type 17 (IL-17A and IL-17F cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially the suppression of cytokine responses in PTB.Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB.

  20. Suppression induction in vivo by a T helper clone?

    DEFF Research Database (Denmark)

    Crispe, I N; Owens, T

    1985-01-01

    We have previously described a helper T cell clone which augments in vivo cytotoxic T cell responses when injected at 10(4) cells per mouse, but not at 10(5) per mouse (Crispe, I. N. et al., Immunology 1984. 52:55). To test whether this dose-response relationship was due to the induction...... of suppression, naive syngeneic mice were injected with 10(5) cloned T helper cells, and their spleen cells were subsequently assayed for suppressive activity in adoptive transfer experiments. Lymphocytes from such mice indeed suppressed an antigen-specific cytotoxic response, but only in the presence...... of the same T helper cell clone freshly added at the time of adoptive transfer. On this basis we argue that the distinction between T helper cell activity and T suppressor-inducer activity corresponds to differences in cell numbers, rather than to two separate cell lineages....

  1. Suppressed Belief

    Directory of Open Access Journals (Sweden)

    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  2. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP10025–33 peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    International Nuclear Information System (INIS)

    Chang, Xiaoli; Xia, Chang-Qing

    2015-01-01

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100 25–33 peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100 25–33 peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100 25–33 peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100 25–33 were significantly increased compared to control groups. Tumor antigen, GP100 25–23 specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100 25–33 -coupled spleen cells leads to potent anti-melanoma immunity. • GP100 25–33 -coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  3. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP100{sub 25–33} peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiaoli [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL32610 (United States)

    2015-12-04

    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100{sub 25–33} peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100{sub 25–33} peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100{sub 25–33} peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100{sub 25–33} were significantly increased compared to control groups. Tumor antigen, GP100{sub 25–23} specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100{sub 25–33}-coupled spleen cells leads to potent anti-melanoma immunity. • GP100{sub 25–33}-coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  4. Tolerogenic Dendritic Cells from Poorly Compensated Type 1 Diabetes Patients Have Decreased Ability To Induce Stable Antigen-Specific T Cell Hyporesponsiveness and Generation of Suppressive Regulatory T Cells

    Czech Academy of Sciences Publication Activity Database

    Dáňová, K.; Grohová, A.; Strnadová, P.; Funda, David P.; Šumník, Z.; Lebl, J.; Cinek, O.; Průhová, Š.; Koloušková, S.; Obermannová, B.; Petruželková, L.; Šedivá, A.; Fundová, Petra; Buschard, K.; Spíšek, R.; Palová-Jelinková, L.

    2017-01-01

    Roč. 198, č. 2 (2017), s. 729-740 ISSN 0022-1767 R&D Projects: GA ČR GA15-24487S Institutional support: RVO:61388971 Keywords : PLACEBO-CONTROLLED TRIAL * GLYCEMIC CONTROL * IMMUNE FUNCTION Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.856, year: 2016

  5. Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols

    International Nuclear Information System (INIS)

    Katiyar, S.K.; Elmets, C.A.; Agarwal, Rajesh; Mukhtar, Hasan

    1995-01-01

    Exposure of skin to UV radiation can cause diverse biological effects, including induction of inflammation, alteration in cutaneous immune cells and impairment of contact hypersensitivity (CHS) responses. Our laboratory has demonstrated that oral feeding as well as topical application of a polyphenolic fraction isolated from green tea (GTP) affords protection against the carcinogenic effects of UVB (280-320 nm) radiation. In this study, we investigated whether GTP could protect against UVB-induced immunosuppression and cutaneous inflammatory responses in C3H mice. Immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UVB-irradiated skin (local suppression) or to a distant site (systemic suppression), while double skin-fold swelling was used as the measure of UVB-induced inflammation. (author)

  6. Interocular suppression

    Science.gov (United States)

    Tuna, Ana Rita; Almeida Neves Carrega, Filipa; Nunes, Amélia Fernandes

    2017-08-01

    The objective of this work is to quantify the suppressive imbalance, based on the manipulation of ocular luminance, between a group of subjects with normal binocular vision and a group of subjects with amblyopia. The result reveals that there are statistically significant differences in interocular dominance between two groups, evidencing a greater suppressive imbalance in amblyopic subjects. The technique used, proved to be a simple, easy to apply and economic method, for quantified ocular dominance. It is presented as a technique with the potential to accompany subjects with a marked dominance in one of the eyes that makes fusion difficult.

  7. Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help B cells for the production of immunoglobulins.

    Science.gov (United States)

    Wu, Changyou; Li, Zitao; Fu, Xiaoying; Yu, Sifei; Lao, Suihua; Yang, Binyan

    2015-10-06

    Natural killer T (NKT) cells from mouse and human play an important role in the immune responses against Mycobacterium tuberculosis. However, the function of CD3(+)TCRvβ11(+) NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that after stimulation with M. tuberculosis antigens, NKT cells isolated from tuberculosis (TB) pleural fluid mononuclear cells (PFMCs) produced IL-21 and other cytokines including IFN-γ, TNF-α, IL-2 and IL-17. IL-21-expressing NKT cells in PFMCs displayed effector memory phenotype, expressing CD45RO(high)CD62L(low)CCR7(low). Moreover, NKT cells expressed high levels of CXCR5 and all of IL-21-expressing NKT cells co-expressed CXCR5. The frequency of BCL-6-expression was higher in IL-21-expressing but not in non-IL-21-expressing CD3(+)TCRvβ11(+) NKT cells. Sorted CD3(+)TCRvβ11(+) NKT cells from PFMCs produced IFN-γ and IL-21 after stimulation, which expressed CD40L. Importantly, CD3(+)TCRvβ11(+) NKT cells provided help to B cells for the production of IgG and IgA. Taken together, our data demonstrate that CD3(+)TCRvβ11(+) NKT cells from a local site of M. tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to secrete IgG and IgA, and may participate in local immune responses against M. tuberculosis infection.

  8. COMPLETE SUPPRESSION OF THE M/N = 2/1 NEOCLASSICAL TEARING MODE USING RADIALLY LOCALIZED ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D AND THE REQUIREMENTS FOR ITER

    International Nuclear Information System (INIS)

    LAHAYE, RJ; LUCE, TC; PETTY, CC; HUMPHREYS, DA; HYATT, AW; PERKINS, FW; PRATER, R; STRAIT, EJ; WADE, MR

    2003-01-01

    A271 COMPLETE SUPPRESSION OF THE M/N = 2/1 NEOCLASSICAL TEARING MODE USING RADIALLY LOCALIZED ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D AND THE REQUIREMENTS FOR ITER. DIII-D experiments demonstrate the first real-time feedback control of the relative location of a narrow beam of microwaves to completely suppress and eliminate a growing tearing mode at the q = 2 surface. long wavelength tearing modes such as the m/n = 2/1 instability are particularly deleterious to tokamak operation. Confinement is seriously degraded by the island, plasma rotation can cease (mode-lock) and disruption can occur. The neoclassical tearing mode (NTM) becomes unstable due to the presence of a helically-perturbed bootstrap current and can be stabilized by replacing the missing bootstrap current in the island O-point by precisely located co-electron cyclotron current drive (ECCD). The optimum position is found when the DIII-D plasma control system (PCS) is put into a search and suppress mode that makes small radial shifts (in about 1 cm steps) in the ECCD location based on minimizing the Mirnov amplitude. Requirements for ITER are addressed

  9. Local increase of arginase activity in lesions of patients with cutaneous leishmaniasis in Ethiopia.

    Directory of Open Access Journals (Sweden)

    Tamrat Abebe

    Full Text Available Cutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood.We have recently shown in an experimental model of cutaneous leishmaniasis that arginase-induced L-arginine metabolism suppresses antigen-specific T cell responses at the site of pathology, but not in the periphery. To test whether these results translate to human disease, we recruited patients presenting with localized lesions of cutaneous leishmaniasis and assessed the levels of arginase activity in cells isolated from peripheral blood and from skin biopsies. Arginase activity was similar in peripheral blood mononuclear cells (PBMCs from patients and healthy controls. In sharp contrast, arginase activity was significantly increased in lesion biopsies of patients with localized cutaneous leishmaniasis as compared with controls. Furthermore, we found that the expression levels of CD3ζ, CD4 and CD8 molecules were considerably lower at the site of pathology as compared to those observed in paired PBMCs.Our results suggest that increased arginase in lesions of patients with cutaneous leishmaniasis might play a role in the pathogenesis of the disease by impairing T cell effector functions.

  10. Distinguishing among potential mechanisms of singleton suppression.

    Science.gov (United States)

    Gaspelin, Nicholas; Luck, Steven J

    2018-04-01

    Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  11. Antigen-specific therapies in multiple sclerosis

    NARCIS (Netherlands)

    Noort, J.M. van

    1998-01-01

    Multiple sclerosis is the major neurological disease of young adults in the western world, affecting about 1 per 1,000. It is characterised by chronic or recurrent lesions of inflammatory damage in the white matter of the central nervous system. Within such lesions, the protective myelin sheath is

  12. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  13. Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model.

    Directory of Open Access Journals (Sweden)

    Zineb Belcaid

    Full Text Available Glioblastoma (GBM is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4 blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137 is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model.GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors.Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4+ and CD8+ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4+ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8+ T cells had no effect on the treatment response.Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in an orthotopic mouse

  14. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation.

    Science.gov (United States)

    Dahl, Viktor; Peterson, Julia; Fuchs, Dietmar; Gisslen, Magnus; Palmer, Sarah; Price, Richard W

    2014-09-24

    Though combination antiretroviral therapy reduces the concentration of HIV-1 RNA in both plasma and cerebrospinal fluid (CSF) below the detection limit of clinical assays, low levels of HIV-1 RNA are frequently detectable in plasma using more sensitive assays. We examined the frequency and magnitude of persistent low-level HIV-1 RNA in CSF and its relation to the central nervous system (CNS) immune activation. CSF and plasma HIV-1 RNA were measured using the single-copy assay with a detection limit of 0.3 copies/ml in 70 CSF and 68 plasma samples from 45 treated HIV-1-infected patients with less than 40 copies/ml of HIV-1 RNA in both fluids by standard clinical assays. We also measured CSF neopterin to assess intrathecal immune activation. Theoretical drug exposure was estimated using the CNS penetration-efficacy score of treatment regimens. CSF HIV-1 RNA was detected in 12 of the 70 CSF samples (17%) taken after up to 10 years of suppressive therapy, compared to 39 of the 68 plasma samples (57%) with a median concentration of less than 0.3 copies/ml in CSF compared to 0.3 copies/ml in plasma (P < 0.0001). CSF samples with detectable HIV-1 RNA had higher CSF neopterin levels (mean 8.2 compared to 5.7 nmol/l; P = 0.0085). Patients with detectable HIV-1 RNA in CSF did not differ in pretreatment plasma HIV-1 RNA levels, nadir CD4 cell count or CNS penetration-efficacy score. Low-level CSF HIV-1 RNA and its association with elevated CSF neopterin highlight the potential for the CNS to serve as a viral reservoir and for persistent infection to cause subclinical CNS injury.

  15. Suppression of superconductivity in La1.85Sr0.15Cu1-yNiyO4: The relevance of local lattice distortions

    International Nuclear Information System (INIS)

    Haskel, D.; Stern, E.A.; Polinger, V.; Dogan, F.

    2001-01-01

    The effect of Ni substitution upon the local structure of La 1.85 Sr 0.15 Cu 1-y Ni y O 4 is commonly neglected when addressing the Ni-induced destruction of the superconducting state at y≅0.03 and a metal-insulator transition at y≅0.05. It is also sometimes assumed that direct substitution of a dopant into the CuO 2 planes has a detrimental effect on superconductivity due to in-plane lattice distortions around the dopants. We present here results from angular-dependent x-ray absorption fine structure (XAFS) measurements at the Ni, La and Sr K-edges of oriented powders of La 1.85 Sr 0.15 Cu 1-y Ni y O 4 with y=0.01, 0.03, 0.06. A special magnetic alignment geometry allowed us to measure pure c and (subform(ab)) oriented XAFS at the Ni K-edge in identical fluorescence geometries. Both the near-edge absorption spectra (XANES) and the XAFS unequivocally show that the NiO 6 octahedra are largely contracted along the c-axis, by ≅ 0.16 Aa. Surprisingly, the Ni-O planar bonds and the Ni-O-Cu/Ni planar buckling angle are nearly identical to their Cu counterparts. The NiO 6 octahedral contraction drives the macroscopic c-axis contraction observed with Ni-doping. The local c-axis strongly fluctuates, due to the different NiO 6 and CuO 6 octahedral configurations and the much stronger bonding of a La +3 ion than a Sr +2 ion to the O(2) apical oxygens. We discuss the relevance of these findings to the mechanisms of T c suppresion and hole-localization by Ni dopants

  16. Absolute quantitative proton NMR spectroscopy based on the amplitude of the local water suppression pulse. Quantification of brain water and metabolites

    DEFF Research Database (Denmark)

    Danielsen, E R; Henriksen, O

    1994-01-01

    Quantification in localized proton NMR spectroscopy has been achieved by various methods in recent years. A new method for absolute quantification is described in this paper. The method simultaneously rules out problems with B1 field inhomogeneity and coil loading, utilizing a relation between th......M and [NAA] = 9.15 +/- 0.74 nM. It is concluded that the quantification method is easily applied in vivo, and that the absolute concentrations obtained are similar to results in other studies except those relying on assumptions of the concentration of an internal reference. The advantage...

  17. Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.

    Science.gov (United States)

    Brown, Monica; Postlethwaite, Arnold E; Myers, Linda K; Hasty, Karen A

    2012-06-01

    Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.

  18. The Suppression of Internal Unrest in South West Africa (Namibia ...

    African Journals Online (AJOL)

    AM Fokkens

    suppression of the Bondelswarts and the actions against Chief Ipumbu. This article .... firepower was an appropriate response to suppress the uprising of local ..... Morris accompanied by Beukes and a commando of 50 men, moved east.

  19. Local IgE production in nonatopic nasal polyposis.

    LENUS (Irish Health Repository)

    Sheahan, Patrick

    2012-02-01

    INTRODUCTION: Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an eosinophilic T-helper 2 inflammatory response. Local production of IgE within nasal polyps (NPs) has been demonstrated, suggesting a role for local IgE in the pathogenesis of NP in atopic CRS patients. We hypothesized that local IgE specific to inhalant allergens may also play a role in the genesis of NP in nonatopic CRS patients. METHODS: Sinus and inferior turbinate tissue was obtained from nonatopic CRSwNP patients (n = 7), chronic rhinosinusitis without nasal polyps (CRSsNP) patients (n = 15), and healthy controls (n = 9) at the time of surgery. ImmunoCAP analysis (Phadia AB, Portage, MI) for 14 common inhalant antigens was performed on tissue homogenates to determine the antigen-specific response. RESULTS: Total IgE levels did not differ in sinus or turbinate tissue between CRSwNP, CRSsNP, or control patients. CRSwNP sinus tissue had higher levels of specific IgE for cockroach and plantain (p = .03) than other groups and elevated Alternaria IgE levels when compared with CRSsNP sinus tissue (p < .05). No significant differences were found for any of the other antigen-specific IgE levels. Fifty-seven percent of CRSwNP polyps demonstrated a polyclonal IgE response, whereas the other 43% had no demonstrable antigen-specific IgE. In contrast, only 17% of CRSsNP patients demonstrated a polyclonal response within sinus tissue, whereas 67% had no detectable antigen-specific IgE. There was no significant difference in levels of IgE in inferior turbinate tissue between the groups (p > .05). CONCLUSIONS: Localized mucosal IgE specific to common inhalant allergens appears to play a role in a subset of CRSwNP patients without evidence of systemic atopy.

  20. Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients.

    Science.gov (United States)

    Greten, T F; Slansky, J E; Kubota, R; Soldan, S S; Jaffee, E M; Leist, T P; Pardoll, D M; Jacobson, S; Schneck, J P

    1998-06-23

    Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1-associated myelopathy/tropic spastic paraparesis patients carried a significant number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19 peptide in their peripheral blood, which were not found in healthy controls. Simultaneous comparison of peripheral blood and cerebrospinal fluid from one patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells were seen consistently over a 9-yr time course in one patient as far as 19 yrs after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19-specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression patterns of activation markers, intracellular TNF-alpha and gamma-interferon depending on the severity of the disease. Thus, visualization of antigen-specific T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated, persist during the chronic phase of the disease, and accumulate in cerebrospinal fluid, showing their pivotal role in the pathogenesis of this neurologic disease.

  1. Strong and multi-antigen specific immunity by hepatitis B core antigen (HBcAg)-based vaccines in a murine model of chronic hepatitis B: HBcAg is a candidate for a therapeutic vaccine against hepatitis B virus.

    Science.gov (United States)

    Akbar, Sheikh Mohammad Fazle; Chen, Shiyi; Al-Mahtab, Mamun; Abe, Masanori; Hiasa, Yoichi; Onji, Morikazu

    2012-10-01

    Experimental evidence suggests that hepatitis B core antigen (HBcAg)-specific cytotoxic T lymphocytes (CTL) are essential for the control of hepatitis B virus (HBV) replication and prevention of liver damage in patients with chronic hepatitis B (CHB). However, most immune therapeutic approaches in CHB patients have been accomplished with hepatitis B surface antigen (HBsAg)-based prophylactic vaccines with unsatisfactory clinical outcomes. In this study, we prepared HBsAg-pulsed dendritic cells (DC) and HBcAg-pulsed DC by culturing spleen DC from HBV transgenic mice (HBV TM) and evaluated the immunomodulatory capabilities of these antigens, which may serve as a better therapy for CHB. The kinetics of HBsAg, antibody levels against HBsAg (anti-HBs), proliferation of HBsAg- and HBcAg-specific lymphocytes, production of antigen-specific CTL, and activation of endogenous DC were compared between HBV TM vaccinated with either HBsAg- or HBcAg-pulsed DC. Vaccination with HBsAg-pulsed DC induced HBsAg-specific immunity, but failed to induce HBcAg-specific immunity in HBV TM. However, immunization of HBV TM with HBcAg-pulsed DC resulted in: (1) HBsAg negativity, (2) production of anti-HBs, and (3) development of HBsAg- and HBcAg-specific T cells and CTL in the spleen and the liver. Additionally, significantly higher levels of activated endogenous DC were detected in HBV TM immunized with HBcAg-pulsed DC compared to HBsAg-pulsed DC (pdamage suggests that HBcAg should be an integral component of the therapeutic vaccine against CHB. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antigen-specific CD8+ T cells in the tumor loci and enhanced anti-tumor effects.

    Directory of Open Access Journals (Sweden)

    Tae Heung Kang

    Full Text Available Interleukin-2 (IL-2 has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci.

  3. Characterization of the antigen-specific CD4+ T cell response induced by prime-boost strategies with CAF01 and CpG adjuvants administered by the intranasal and subcutaneous routes

    Directory of Open Access Journals (Sweden)

    Annalisa eCiabattini

    2015-08-01

    Full Text Available The design of heterologous prime-boost vaccine combinations that optimally shape the immune response is of critical importance for the development of next generation vaccines. Here we tested different prime-boost combinations using the tuberculosis vaccine antigen H56 with CAF01 or CpG ODN 1821 adjuvants, administered by the parenteral and nasal routes. By using peptide-MHC class II tetramers, antigen-specific CD4+ T cells were tracked following primary and booster immunizations. Both parenteral priming with H56 plus CAF01 and nasal priming with H56 plus CpG elicited significant expansion of CD4+ tetramer-positive T cells in the spleen, however only parenterally primed cells responded to booster immunization. Subcutaneous priming with H56 and CAF01 followed by nasal boosting with H56 and CpG showed the greater expansion of CD4+ tetramer-positive T cells in the spleen and lungs compared to all the other homologous and heterologous prime-boost combinations. Nasal boosting exerted a recruitment of primed CD4+ T cells into lungs that was stronger in subcutaneously than nasally primed mice, in accordance with different chemokine receptor expression induced by primary immunization. These data demonstrate that subcutaneous priming is fundamental for eliciting CD4+ T cells that can be efficiently boosted by the nasal route and results in the recruitment of antigen-experienced cells into the lungs. Combination of different vaccine formulations and routes of delivery for priming and boosting is a strategic approach for improving and directing vaccine-induced immune responses.

  4. Mechanisms of tolerance in murine radiation bone marrow chimeras. II. Absence of nonspecific suppression in mature chimeras

    International Nuclear Information System (INIS)

    Auchincloss, H. Jr.; Sachs, D.H.

    1983-01-01

    Spleen cells from a series of allogeneic bone marrow chimeras were sensitized in vitro with stimulator cells from major histocompatibility complex recombinant strains of mice. The combinations were chosen such that both tolerated (host or donor) and nontolerated (third-party) antigens were present on the same stimulator cells in order to determine whether the tolerated host antigens might elicit nonspecific suppressor mechanisms affecting the cell-mediated lympholysis (CML) response to the nontolerated antigens. No evidence for such nonspecific suppression was obtained in several types of assays. Therefore, if suppressor mechanisms exist that mediate such tolerance in mature allogeneic chimeras then these mechanisms must be highly antigen-specific

  5. Planck-suppressed operators

    International Nuclear Information System (INIS)

    Assassi, Valentin; Baumann, Daniel; Green, Daniel; McAllister, Liam

    2014-01-01

    We show that the recent Planck limits on primordial non-Gaussianity impose strong constraints on light hidden sector fields coupled to the inflaton via operators suppressed by a high mass scale Λ. We study a simple effective field theory in which a hidden sector field is coupled to a shift-symmetric inflaton via arbitrary operators up to dimension five. Self-interactions in the hidden sector lead to non-Gaussianity in the curvature perturbations. To be consistent with the Planck limit on local non-Gaussianity, the coupling to any hidden sector with light fields and natural cubic couplings must be suppressed by a very high scale Λ > 10 5 H. Even if the hidden sector has Gaussian correlations, nonlinearities in the mixing with the inflaton still lead to non-Gaussian curvature perturbations. In this case, the non-Gaussianity is of the equilateral or orthogonal type, and the Planck data requires Λ > 10 2 H

  6. Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2001-06-01

    In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

  7. COMPARISON STUDY OF COUGH SUPPRESSION DURING FLEXIBLE BRONCHOSCOPY USING LOCAL ANAESTHESIA IN DIFFERENT TECHNIQUES- (10% LIGNOCAINE SPRAY + 2% LIGNOCAINE AS YOU GO VERSUS (4% LIGNOCAINE NEBULISATION + 2% LIGNOCAINE AS YOU GO

    Directory of Open Access Journals (Sweden)

    Koushik Muthu Raja Mathivanan

    2017-08-01

    Full Text Available BACKGROUND Anaesthesia for bronchoscopy poses unique challenges for the pulmonologist. By definition, bronchoscopy is an endoscopic technique to visualise the inside of the airways, it is a pivotal diagnostic and therapeutic tool in Pulmonary Medicine. Rigid bronchoscopy is usually done for diagnosis and treatment of intra and/or extra luminal obstruction in the airway for adults and children. With the development of fibreoptic and advanced electronic technology, the flexible bronchoscope has replaced the rigid bronchoscope for most diagnostic and some therapeutic indications. Rigid bronchoscopy requires general anaesthesia, however, flexible bronchoscopy can be performed with conscious sedation supplemented with local anaesthesia. The aim of the study is to- 1. Assess the effect of local anaesthesia on cough suppression during flexible bronchoscopy, when given by two different methods. 2. Compare the degree of cough and patient comfort while using “10% lignocaine spray + 2% lignocaine as you go technique, versus 4% lignocaine nebulisation + 2% lignocaine as you go technique.” MATERIALS AND METHODS It is a prospective study done on 50 consecutive patients undergoing diagnostic flexible bronchoscopy from December 2016 to February 2017. The study groups were assembled by block randomisation technique to receive lignocaine (local anaesthesia as either “as you go” and “spray” or “as you go” and “nebulisation”. Institutional Ethics Committee clearance was obtained prior to commencement of the study. RESULTS The study involving 50 patients and statistical analysis illustrated that in 2% lignocaine as you go + 10% lignocaine spray “no cough” and “mild cough” is 18 out of sample 25, which is 72%. Hence, “10% lignocaine spray + 2% lignocaine as you go” is better than “4% lignocaine nebulisation + 2% lignocaine as you go” technique. There was no significant arrhythmias in any of the patients. The dose of lidocaine is

  8. Suppression of immune response to Lol pI by administration of idiotype.

    Science.gov (United States)

    Boutin, Y; Hébert, J

    1995-03-01

    Allergic diseases are characterized by an increased production of specific IgE antibodies. Suppression of IgE antibody production may be accomplished through idiotypic manipulation. Using an animal model, we explored the effects of anti-Lol pI monoclonal antibody administration on the subsequent IgE and IgG antibody response against Lol pI. Mice were treated with an anti-Lol pI monoclonal antibody (290A-167), which resulted in the production of anti-idiotypic antibodies as evidenced by their ability to bind to the Fab fraction of 290A-167 and to inhibit the binding of rabbit polyclonal anti-idiotypic antibodies to 290A-167. The animals were then immunized with Lol pI adsorbed onto alum, and the immune response to the protein was analyzed. Antigen-specific IgG1 and IgE responses were strongly suppressed as determined by immunoassay. Suppression of anti-Lol pI IgE antibodies was confirmed by a reduction of end-point titers measured by passive cutaneous anaphylaxis. The suppression of antigen-specific antibody was accompanied by a reduction of anti-Lol pI antibody-producing spleen cells. These data indicate that pretreatment with 290A-167 can strongly downregulate the IgE response to the main allergen of ryegrass pollen, which is associated with an increase in anti-idiotypic antibodies. This approach could provide rapid, long-term hyposensitization in patients with grass pollen allergy.

  9. Cannabinoid Receptor 2 (CB2 Plays a Role in the Generation of Germinal Center and Memory B Cells, but Not in the Production of Antigen-Specific IgG and IgM, in Response to T-dependent Antigens.

    Directory of Open Access Journals (Sweden)

    Sreemanti Basu

    Full Text Available The cannabinoid receptor 2 (CB2 has been reported to modulate B cell functions including migration, proliferation and isotype class switching. Since these processes are required for the generation of the germinal center (GC and antigen-specific plasma and memory cells following immunization with a T-dependent antigen, CB2 has the capacity to alter the quality and magnitude of T-dependent immune responses. To address this question, we immunized WT and CB2(-/- mice with the T-dependent antigen 4-hydroxy-3-nitrophenylacetyl (NP-chicken-gamma-globulin (CGG and measured GC B cell formation and the generation of antigen-specific B cells and serum immunoglobulin (Ig. While there was a significant reduction in the number of splenic GC B cells in CB2(-/- mice early in the response there was no detectable difference in the number of NP-specific IgM and IgG1 plasma cells. There was also no difference in NP-specific IgM and class switched IgG1 in the serum. In addition, we found no defect in the homing of plasma cells to the bone marrow (BM and affinity maturation, although memory B cell cells in the spleen were reduced in CB2(-/- mice. CB2-deficient mice also generated similar levels of antigen-specific IgM and IgG in the serum as WT following immunization with sheep red blood cells (sRBC. This study demonstrates that although CB2 plays a role in promoting GC and memory B cell formation/maintenance in the spleen, it is dispensable on all immune cell types required for the generation of antigen-specific IgM and IgG in T-dependent immune responses.

  10. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

  11. Deconstructing continuous flash suppression

    OpenAIRE

    Yang, Eunice; Blake, Randolph

    2012-01-01

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

  12. Suppression of the cutaneous immune response following topical application of the prostaglandin PGE2

    International Nuclear Information System (INIS)

    Rheins, L.A.; Barnes, L.; Amornsiripanitch, S.; Collins, C.E.; Nordlund, J.J.

    1987-01-01

    UVB irradiation (290-320 nm) and topical applications of arachidonic acid (AA) in mice decrease the number of identifiable Langerhans cells and alter the cutaneous immune response. Application of contact allergens such as dinitrofluorobenzene (DNFB) to irradiated or AA-treated skin induces antigen-specific tolerance. Indomethacin (IM), a cyclooxygenase inhibitor, administered orally to mice prior to UVB irradiation or prior to the topical application of arachidonic acid, abrogates suppression of contact hypersensitivity (CHS) to DNFB. This suggests a byproduct of arachidonic acid generated through the cyclooxygenase pathway may be involved in the immune suppression. Topical application of various prostaglandins (PGE2, PGD2, PGF2 alpha, and CTXA2) did not cause alterations in the population density of the identifiable Ia+ dendritic Langerhans cells. PGE2, but no other tested agent, produced a suppression of the CHS response to DNFB. These observations suggests that of the various prostaglandins, PGE2 might be one of several biochemical signals which mediate the suppression of contact hypersensitivity reactions following ultraviolet radiation exposure. However, the mechanisms by which PGE2 produces its suppressive effects have not been identified

  13. Oral administration of type-II collagen peptide 250-270 suppresses specific cellular and humoral immune response in collagen-induced arthritis.

    Science.gov (United States)

    Zhu, Ping; Li, Xiao-Yan; Wang, Hong-Kun; Jia, Jun-Feng; Zheng, Zhao-Hui; Ding, Jin; Fan, Chun-Mei

    2007-01-01

    Oral antigen is an attractive approach for the treatment of autoimmune and inflammatory diseases. Establishment of immune markers and methods in evaluating the effects of antigen-specific cellular and humoral immune responses will help the application of oral tolerance in the treatment of human diseases. The present article observed the effects of chicken collagen II (CII), the recombinant polymerized human collagen II 250-270 (rhCII 250-270) peptide and synthesized human CII 250-270 (syCII 250-270) peptide on the induction of antigen-specific autoimmune response in rheumatoid arthritis (RA) peripheral blood mononuclear cells (PBMC) and on the specific cellular and humoral immune response in collagen-induced arthritis (CIA) and mice fed with CII (250-270) prior to immunization with CII. In the study, proliferation, activation and intracellular cytokine production of antigen-specific T lymphocytes were simultaneously analyzed by bromodeoxyuridine (BrdU) incorporation and flow cytometry at the single-cell level. The antigen-specific antibody and antibody-forming cells were detected by ELISA and ELISPOT, respectively. CII (250-270) was found to have stimulated the response of specific lymphocytes in PBMC from RA patients, including the increase expression of surface activation antigen marker CD69 and CD25, and DNA synthesis. Mice, fed with CII (250-270) before CII immunization, had significantly lower arthritic scores than the mice immunized with CII alone, and the body weight of the former increased during the study period. Furthermore, the specific T cell activity, proliferation and secretion of interferon (IFN)-gamma in spleen cells were actively suppressed in CII (250-270)-fed mice, and the serum anti-CII, anti-CII (250-270) antibody activities and the frequency of specific antibody-forming spleen cells were significantly lower in CII (250-270)-fed mice than in mice immunized with CII alone. These observations suggest that oral administration of CII (250-270) can

  14. Deconstructing continuous flash suppression.

    Science.gov (United States)

    Yang, Eunice; Blake, Randolph

    2012-03-08

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

  15. Suppressive competition: how sounds may cheat sight.

    Science.gov (United States)

    Kayser, Christoph; Remedios, Ryan

    2012-02-23

    In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex activation directly engages local GABAergic circuits in V1 to induce sound-driven hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds can directly suppress V1 activity and visual driven behavior. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Sodium fire suppression

    Energy Technology Data Exchange (ETDEWEB)

    Malet, J C [DSN/SESTR, Centre de Cadarache, Saint-Paul-lez-Durance (France)

    1979-03-01

    Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

  17. Sodium fire suppression

    International Nuclear Information System (INIS)

    Malet, J.C.

    1979-01-01

    Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

  18. Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment

    Directory of Open Access Journals (Sweden)

    Alberto N. Peón

    2017-01-01

    Full Text Available A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE, an animal model of the human disease multiple sclerosis (MS. The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES that may suppress EAE development were sought for. Interestingly, it was discovered that TcES was able to suppress EAE development with more potency than dexamethasone; moreover, TcES treatment was still effective even when inoculated at later stages after the onset of EAE. Importantly, the TcES treatment was able to induce a range of Th2-type cytokines, while suppressing Th1 and Th17 responses. Both the polyclonal and the antigen-specific proliferative responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in association with a potent recruitment of suppressor cell populations. Peritoneal inoculation of TcES was able to direct the normal inflammatory cell traffic to the site of injection, thus modulating CNS infiltration, which may work along with Th2 immune polarization and lymphocyte activation impairment to downregulate EAE development.

  19. Pressure suppression device

    International Nuclear Information System (INIS)

    Mizumachi, Wataru; Fukuda, Akira; Kitaguchi, Hidemi; Shimizu, Toshiaki.

    1976-01-01

    Object: To relieve and absorb impact wave vibrations caused by steam and non-condensed gases releasing into the pressure suppression chamber at the time of an accident. Structure: The reactor container is filled with inert gases. A safety valve attached main steam pipe is provided to permit the excessive steam to escape, the valve being communicated with the pressure suppression chamber through an exhaust pipe. In the pressure suppression chamber, a doughnut-like cylindrical outer wall is filled at its bottom with pool water to condense the high temperature vapor released through the exhaust pipe. A head portion of a vent tube which leads the exhaust pipe is positioned at the top, and a down comer and an exhaust vent tube are locked by means of steady rests. At the bottom is mounted a pressure adsorber device which adsorbs a pressure from the pool water. (Kamimura, M.)

  20. Thyroxin hormone suppression treatment

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    One of the important modalities of treatment of thyroid cancer (TC) after surgery is the administration of thyroxin as an adjuvant treatment. The analysis supports the theory that thyroid suppression plays an important role in patient management. 300 μg of thyroxin, as this is an adequate dose for suppression is given. Ideally the dose should be tailored by testing s-TSH levels. However, since a large number of the patients come from out station cities and villages this is impractical. We therefore depend on clinical criteria of hyperthyroid symptoms and adjust the dose. Very few patients need such adjustment

  1. Shielding design of ITER pressure suppression system

    International Nuclear Information System (INIS)

    Yamauchi, Michinori; Sato, Satoshi; Nishitani, Takeo; Kawasaki, Hiromitsu

    2006-01-01

    The duct shield from streaming D-T neutrons has been designed for the ITER pressure suppression system. Streaming calculations are performed with the DUCT-III code for the region from the inlet of the pressure relief line to the rupture disk. Next, the neutron permeation through the shield is studied by Monte Carlo calculations with the MCNP code. It is found that 0.15 m thick iron shield is enough to suppress the permeating component from the outside. In addition, it is suggested that the volume of the shield can be reduced by about 30% if the optimized iron shield structure having localized thickness across intense permeation paths is employed to shield the pressure suppression line. (T.I.)

  2. Pressure suppressing device

    International Nuclear Information System (INIS)

    Naito, Makoto.

    1980-01-01

    Purpose: To prevent the pressure in the reactor container from excessively increasing even when vapor leaks from the dry well to a space of the suppression chamber, without passing though the suppression pool at the time of loss of coolant accident. Constitution: When vapor of a high temperature and a high pressure at the time of loss of coolant accident flows from the dry well to the suppression chamber without passing through suppression pool water, vapor dose not condense with pool water, and therefore the pressure within the chamber abnormally increases. For this reason, this abnormal pressure is detected by a pressure detector thereby to start the operations of a blower and a pump. By starting the blower, the pressure in the dry well becomes lower than the pressure in the chamber, and vapor entirely passes through the pool water and entirely condenses with the pool water. By starting the pump, the pool water is sprayed over the space of the chamber, and vapor in the space is condensed. (Yoshino, Y.)

  3. Induction of Interleukin-10 Producing Dendritic Cells As a Tool to Suppress Allergen-Specific T Helper 2 Responses

    Directory of Open Access Journals (Sweden)

    Stefan Schülke

    2018-03-01

    Full Text Available Dendritic cells (DCs are gatekeepers of the immune system that control induction and polarization of primary, antigen-specific immune responses. Depending on their maturation/activation status, the molecules expressed on their surface, and the cytokines produced DCs have been shown to either elicit immune responses through activation of effector T cells or induce tolerance through induction of either T cell anergy, regulatory T cells, or production of regulatory cytokines. Among the cytokines produced by tolerogenic DCs, interleukin 10 (IL-10 is a key regulatory cytokine limiting und ultimately terminating excessive T-cell responses to microbial pathogens to prevent chronic inflammation and tissue damage. Because of their important role in preventing autoimmune diseases, transplant rejection, allergic reactions, or in controlling chronic inflammation DCs have become an interesting tool to modulate antigen-specific immune responses. For the treatment of allergic inflammation, the aim is to downregulate allergen-specific T helper 2 (Th2 responses and the associated clinical symptoms [allergen-driven Th2 activation, Th2-driven immunoglobulin E (IgE production, IgE-mediated mast cell and basophil activation, allergic inflammation]. Here, combining the presentation of allergens by DCs with a pro-tolerogenic, IL-10-producing phenotype is of special interest to modulate allergen-specific immune responses in the treatment of allergic diseases. This review discusses the reported strategies to induce DC-derived IL-10 secretion for the suppression of allergen-specific Th2-responses with a focus on IL-10 treatment, IL-10 transduction, and the usage of both whole bacteria and bacteria-derived components. Interestingly, while IL-10-producing DCs induced either by IL-10 treatment or IL-10 transduction are arrested in an immature/semi-mature state, treatment of DCs with live or killed bacteria as well as isolated bacterial components results in the induction of

  4. J/Ψ suppression

    International Nuclear Information System (INIS)

    Giubellino, P.; Abreu, M.C.; Alessandro, B.; Alexa, C.; Arnaldi, R.; Astruc, J.; Atayan, M.; Baglin, C.; Baldit, A.; Bedjidian, M.; Bellaiche, F.; Beole, S.; Boldea, V.; Bordalo, P.; Bussiere, A.; Capony, V.; Casagrande, L.; Castor, J.; Chambon, T.; Chaurand, B.; Chevrot, I.; Cheynis, B.; Chiavassa, E.; Cicalo, C.; Comets, M.P.; Constantinescu, S.; Cruz, J.; De Falco, A.; De Marco, N.; Dellacasa, G.; Devaux, A.; Dita, S.; Drapier, O.; Espagnon, B.; Fargeix, J.; Filippov, S.N.; Fleuret, F.; Force, P.; Gallio, M.; Gavrilov, Y.K.; Gerschel, C.; Giubellino, P.; Golubeva, M.B.; Gonin, M.; Grigorian, A.A.; Grossiord, J.Y.; Guber, F.F.; Guichard, A.; Gulkaninan, H.; Hakobyan, R.; Haroutunian, R.; Idzik, M.; Jouan, D.; Karavitcheva, T.L.; Kluberg, L.; Kurepin, A.B.; Le Bornec, Y.; Lourenco, C.; Mac Cormick, M.; Macciotta, P.; Marzari-Chiesa, A.; Masera, M.; Masoni, A.; Mehrabyan, S.; Mourgues, S.; Musso, A.; Ohlsson-Malek, F.; Petiau, P.; Piccotti, A.; Pizzi, J.R.; Prado da Silva, W.L.; Puddu, G.; Quintans, C.; Racca, C.; Ramello, L.; Ramos, S.; Rato-Mendes, P.; Riccati, L.; Romana, A.; Sartori, S.; Saturnini, P.; Scomparin, E.; Serci, S.; Shahoyan, R.; Silva, S.; Soave, C.; Sonderegger, P.; Tarrago, X.; Temnikov, P.; Topilskaya, N.S.; Usai, G.; Vale, C.; Vercellin, E.; Willis, N.

    1999-01-01

    The cross section for J/Ψ production in Pb-Pb interactions at 158 GeV per nucleon is measured at the CERN SPS by the NA50 experiment. The final results from the 1995 run are presented here together with preliminary ones from the high-statistics 1996 run. An anomalous J/Ψ suppression is observed in Pb-Pb collisions as compared to extrapolations of the previous results obtained by the NA38 experiment with proton and lighter ion beams. The results of the two runs are in good agreement. The results from the 1996 run allow the study of the onset of the anomalous suppression within the same set of data, showing evidence of a sharp change of behaviour around a value of neutral transverse energy, as measured by our electromagnetic calorimeter, of about 50 GeV

  5. Suppression of the invasive plant mile-a-minute (Mikania micrantha) by local crop sweet potato (Ipomoea batatas) by means of higher growth rate and competition for soil nutrients.

    Science.gov (United States)

    Shen, Shicai; Xu, Gaofeng; Clements, David Roy; Jin, Guimei; Chen, Aidong; Zhang, Fudou; Kato-Noguchi, Hisashi

    2015-01-28

    There are a variety of ways of increasing crop diversity to increase agricultural sustainability and in turn having a positive influence on nearby natural ecosystems. Competitive crops may provide potent management tools against invasive plants. To elucidate the competitive mechanisms between a sweet potato crop (Ipomoea batatas) and an invasive plant, mile-a-minute (Mikania micrantha), field experiments were carried out in Longchuan County of Yunnan Province, Southwest China, utilizing a de Wit replacement series. The trial incorporated seven ratios of sweet potato and mile-a-minute plants in 25 m(2) plots. In monoculture, the total biomass, biomass of adventitious root, leafstalk length, and leaf area of sweet potato were all higher than those of mile-a-minute, and in mixed culture the plant height, branch, leaf, stem node, adventitious root, flowering and biomass of mile-a-minute were suppressed significantly (P competition was less than interspecific competition. The competitive balance index of sweet potato demonstrated a higher competitive ability than mile-a-minute. Except pH, other soil nutrient contents of initial soil (CK) were significantly higher than those of seven treatments. The concentrations of soil organic matter, total N, total K, available N, available P, available K, exchange Ca, exchange Mg, available Mn, and available B were significantly greater (P competition of sweet potato in the mixture. Evidently sweet potato has a competitive advantage in terms of plant growth characteristics and greater absorption of soil nutrients. Thus, planting sweet potato is a promising technique for reducing infestations of mile-a-minute, providing weed management benefits and economic returns from harvest of sweet potatoes. This study also shows the potential value of replacement control methods which may apply to other crop-weed systems or invaded natural ecosystems.

  6. Boiling Suppression in Convective Flow

    International Nuclear Information System (INIS)

    Aounallah, Y.

    2004-01-01

    The development of convective boiling heat transfer correlations and analytical models has almost exclusively been based on measurements of the total heat flux, and therefore on the overall two-phase heat transfer coefficient, when the well-known heat transfer correlations have often assumed additive mechanisms, one for each mode of heat transfer, convection and boiling. While the global performance of such correlations can readily be assessed, the predictive capability of the individual components of the correlation has usually remained elusive. This becomes important when, for example, developing mechanistic models for subcooled void formation based on the partitioning of the wall heat flux into a boiling and a convective component, or when extending a correlation beyond its original range of applications where the preponderance of the heat transfer mechanisms involved can be significantly different. A new examination of existing experimental heat transfer data obtained under fixed hydrodynamic conditions, whereby the local flow conditions are decoupled from the local heat flux, has allowed the unequivocal isolation of the boiling contribution over a broad range of thermodynamic qualities (0 to 0.8) for water at 7 MPa. Boiling suppression, as the quality increases, has consequently been quantified, thus providing valuable new insights on the functionality and contribution of boiling in convective flows. (author)

  7. Ni-induced local distortions in La1.85Sr0.15Cu1-yNiyO4 and their relevance to Tc suppression: An angular-resolved XAFS study

    International Nuclear Information System (INIS)

    Haskel, Daniel; Stern, Edward A.; Polinger, Victor; Dogan, Fatih

    2001-01-01

    We present results from angular-resolved x-ray-absorption fine-structure (XAFS) measurements at the Ni, La, and Sr K edges of oriented powders of La 1.85 Sr 0.15 Cu 1-y Ni y O 4 , with y=0.01, 0.03, 0.06. A special magnetic alignment procedure allowed us to measure pure c- and ab-oriented XAFS at the Ni K edge in identical fluorescence geometries. Both the x-ray-absorption near-edge structure and the XAFS unequivocally show that the NiO 6 octahedra are contracted along the c axis by ∼0.32 angstrom relative to CuO 6 octahedra while the in-plane distances of NiO 6 and CuO 6 octahedra are the same within 0.01 angstrom. The NiO 6 octahedral contraction drives the average c axis contraction measured by diffraction with increasing content of Ni. The local c axis shows strong spatial fluctuations, due to the different NiO 6 and CuO 6 octahedral configurations and the stronger bonding of a La 3+ ion than a Sr 2+ ion to the O(2) apical oxygens of such octahedra. We discuss the relevance of these findings to the mechanisms of loss of superconductivity at y∼0.03 and hole localization above y∼0.05 by Ni dopants

  8. Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination

    NARCIS (Netherlands)

    Mahan, Alison E.; Jennewein, Madeleine F.; Suscovich, Todd; Dionne, Kendall; Tedesco, Jacquelynne; Chung, Amy W.; Streeck, Hendrik; Pau, Maria; Schuitemaker, Hanneke; Francis, Don; Fast, Patricia; Laufer, Dagna; Walker, Bruce D.; Baden, Lindsey; Barouch, Dan H.; Alter, Galit

    2016-01-01

    Antibody effector functions, such as antibody-dependent cellular cytotoxicity, complement deposition, and antibody-dependent phagocytosis, play a critical role in immunity against multiple pathogens, particularly in the absence of neutralizing activity. Two modifications to the IgG constant domain

  9. Dissection and manipulation of antigen-specific T cell responses

    NARCIS (Netherlands)

    Schepers, Koen

    2006-01-01

    T cells recognize pathogen-derived antigens and are crucial for fighting pathogens such as viruses and bacteria. In addition, T cells are able to recognize and attack certain types of tumors, in particular virally induced tumors. In this thesis we aimed 1) to obtain more insight into

  10. The pressure suppression system

    International Nuclear Information System (INIS)

    Aust, E.

    1985-01-01

    Nuclear plants with boiling water reactors have a safety containment with a pressure suppression system (PSS). Proceeding on significant self-developments, today the three PSS-lines of General Electric Co. (GE), Kraftwerk Union AG (KWU) and ASEA-ATOM are predominant, which are currently represented by the MARK III type, the KWU type 72 and the BWR 75 containment. In addition, there are special developments for the nuclear ship propulsion and for the pressurized water reactors in the Soviet Union. Key design values of the PSS allow a first valuation of its loads during a hypothetical loss-of-coolant accident. (orig.) [de

  11. Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology

    International Nuclear Information System (INIS)

    De Fabo, E.C.; Noonan, F.P.

    1983-01-01

    UV irradiation of mice causes a systemic immune alteration that can be detected either by suppression of the immunologic rejection of UV-induced tumors, or by suppression of contact hypersensitivity (CHS). Suppression of these two immunologic responses has similar photobiologic characteristics and in both cases is associated with the generation of antigen-specific suppressor T cells. To identify whether a specific photoreceptor for this effect exists, the relative wavelength effectiveness (action spectrum) was determined for the UV-induced suppression of CHS. Narrow bands of UV (half bandwidth 3 nm) were used at 10 wavelengths from 250 to 320 nm to obtain dose-response curves. The action spectrum derived from the dose-response curves has a maximum between 260 and 270 nm, a shoulder at 280-290 nm, and declines steadily to approximately 3% of maximum at 320 nm. The finding of such a clearly defined wavelength dependence implies the presence of a specific photoreceptor for this effect. Removing the stratum corneum by tape stripping before UV irradiation prevented the suppression of CHS using 254-nm radiation, suggesting the photoreceptor is superficially located in the skin. The hypothesis is advanced that the photoreceptor for systemic UV-induced immunosuppression of contact hypersensitivity may be urocanic acid. As such, it may also play a role in UV-induced carcinogenesis via the production of tumor-specific suppressor cells

  12. Radiation effluent suppression system

    International Nuclear Information System (INIS)

    Watanabe, Atsushi.

    1992-01-01

    In a radiation release suppression system upon accident, an electromotive valve, a pneumatic operation valve or a manual operation valve is disposed to gas ventilation pipelines which are extended from both of a dry well and a wet well of a reactor container to a stuck. In addition, a combination filter of a metal fiber filter made of stainless steel etc. and an activated carbon fiber filter is disposed in the midway of pipelines in a reactor building. With such a constitution, the inside of the container can be depressurized (prevention of ruptures) and the amount of radioactive substances released to circumstances is remarkably suppressed by the effect of radioactive substance capturing effect of the metal fiber filter made of stainless steel etc. disposed in the vent pipe in the container and a radioactive substance capturing effect by the combination filter of the metal fiber filter made of stainless steel, etc. and the activated carbon fiber filter disposed in the gas ventilation pipelines even upon occurrence of an accident exceeding design basis. Systems can be simplified and minimized, and cost down can also be attained. (N.H.)

  13. Interferon-β Suppresses Murine Th1 Cell Function in the Absence of Antigen-Presenting Cells

    Science.gov (United States)

    Boivin, Nicolas; Baillargeon, Joanie; Doss, Prenitha Mercy Ignatius Arokia; Roy, Andrée-Pascale; Rangachari, Manu

    2015-01-01

    Interferon (IFN)-β is a front-line therapy for the treatment of the relapsing-remitting form of multiple sclerosis. However, its immunosuppressive mechanism of function remains incompletely understood. While it has been proposed that IFN-β suppresses the function of inflammatory myelin antigen-reactive T cells by promoting the release of immunomodulatory cytokines such as IL-27 from antigen-presenting cells (APCs), its direct effects on inflammatory CD4+ Th1 cells are less clear. Here, we establish that IFN-β inhibits mouse IFN-γ+ Th1 cell function in the absence of APCs. CD4+ T cells express the type I interferon receptor, and IFN-β can suppress Th1 cell proliferation under APC-free stimulation conditions. IFN-β-treated myelin antigen-specific Th1 cells are impaired in their ability to induce severe experimental autoimmune encephalomyelitis (EAE) upon transfer to lymphocyte-deficient Rag1-/- mice. Polarized Th1 cells downregulate IFN-γ and IL-2, and upregulate the negative regulatory receptor Tim-3, when treated with IFN-β in the absence of APCs. Further, IFN-β treatment of Th1 cells upregulates phosphorylation of Stat1, and downregulates phosphorylation of Stat4. Our data indicate that IFN-γ-producing Th1 cells are directly responsive to IFN-β and point to a novel mechanism of IFN-β-mediated T cell suppression that is independent of APC-derived signals. PMID:25885435

  14. Screening for suppression in young children: the Polaroid Suppression test

    NARCIS (Netherlands)

    Pott, J.W.R.; Oosterveen, DK; Van Hof-van Duin, J

    1998-01-01

    Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

  15. Antibody-mediated allotype suppression in adult mice: the role of antigen, effector isotype and regulatory T cells.

    Science.gov (United States)

    Curling, E M; Dresser, D W

    1984-10-01

    It has been reported (Contemp. Top. Immunobiol. 1974. 3:41) that allotype-specific T suppressor cells can be induced after monoclonal anti-allotype treatment of neonatal (BALB/c X SJL)F1 (Igha/b) mice. Here we show that (BALB/c X CB20)F1 adult-derived spleen cells (SC) are, by contrast, potently suppressed by monoclonal allotype-specific reagents, (when transferred into irradiated BALB/c recipients) in the absence of primary T suppressor cell induction. Such suppression is only induced in activated B cells [exposed to lipopolysaccharide or sheep red blood cells (SRBC)], and is probably dependent on the isotype of the anti-allotype sera administered. For example, two independently produced IgG1 monoclonal reagents raised against the Igh-1b allotype were poorly suppressive or nonsuppressive, whereas an IgG3 and an IgG2a monoclonal antibody induced a 90% suppression of the target allotype in transferred adult SC. It was found that suppression was not due to a depletion of antigen-specific T cell help since: (a) the addition of SRBC-educated T cells did not break suppression and (b) suppressed SC were as good a source of T cell help as normal SC, in the response of virgin or memory B cell (Thy-1-depleted) responses to SRBC in vivo. Suppression was maintained in suppressed cells which had been rechallenged with SRBC after transfer into a second irradiated recipient, but was not induced in normal SC when these were admixed with an equal number from this suppressed SC population. These findings point to a possible mechanism for the regulation of B cell expression, through the formation of an antibody-Ig receptor complex at the surface of the B lymphocyte. After complexing the target cell is either deleted or inactivated. The response to SRBC was reduced or ablated for at least 70 days after treatment with a single dose of anti-allotype serum.

  16. Pressure suppression device

    International Nuclear Information System (INIS)

    Yoshida, Toyokazu.

    1976-01-01

    Purpose: To provide a pressure suppression device for a gas cooled reactor wherein the coolant is discharged in a reactor building by a loss-of-coolant accident or the like, the increase in the pressure and temperature is controlled and thermal energy of the discharged coolant of high temperature and high pressure can be absorbed. Constitution: A low heat source unit is provided at the upper part in an inner space of a reactor building provided around the reactor, and at the upper part of the low heat source unit a stirring fan for mixing gas within the building, and a low heat source circulating the low heat source through a pipe is connected to the low heat source unit. The low heat source unit is provided with the pipe arranged in a spiral shape at the upper part of the space of the unit, and a large number of fins are provided at the outer surface of the pipe for increasing the transmission area and improve the heat exchange. When the coolant of high temperature and high pressure has been lost in the building, the thermal energy of the coolant is absorbed by the low heat source unit. (Aizawa, K.)

  17. Immune response gene control of collagen reactivity in man: collagen unresponsiveness in HLA-DR4 negative nonresponders is due to the presence of T-dependent suppressive influences

    International Nuclear Information System (INIS)

    Solinger, A.M.; Stobo, J.D.

    1982-01-01

    To determine whether the failure to detect collagen reactivity in nonresponders represents an absence of collagen-reactive T cells or a preponderance of suppressive influences, the peripheral blood mononuclear cells from HLA-DR4 - individuals were subjected to three procedures capable of separating suppressive influences from LIF-secreting cells; irradiation (1000 rad), discontinuous gradient fractionation, and cytolysis with the monoclonal antibody OKT 8. Each procedure resulted in the specific appearance of reactivity to collagen, which was identical to that seen in HLA-DR4 + individuals with regard to its cellular requirements and antigenic specificity. Addition of unresponsive (i.e., nonirradiated or low-density T cells) to responsive (i.e., irradiated or high-density T cells) autologous populations resulted in specific suppression of collagen reactivity. Radiation-sensitive suppressive influences could not be detected in HLA-DR4 + collagen responders.These studies indicate that the expression of T-dependent reactivity to collagen in man reflects the net influence of collage-reactive vs collagen-suppressive T cells. Moreover, it is the influence of HLA-D-linked genes on the development of suppressive influences rather than on the development of collagen-reactive, LIF-secreting T cells that serves to distinguish HLA-DR4 + collagen responders from HLA-DR4 - collagen nonresponders

  18. Synchronization and suppression of chaos in non-locally coupled ...

    Indian Academy of Sciences (India)

    Coupled map lattices have been intensively investigated as models to understand many spatiotemporal phenomena observed in extended system, and consequently spatiotemporal chaos. We used the complex order parameter to quantify chaos synchronization for a one-dimensional chain of coupled logistic maps with a ...

  19. Use of locally available flavouring materials in suppressing the ...

    African Journals Online (AJOL)

    African Journal of Food, Agriculture, Nutrition and Development ... effect of blending soymilk with pineapple, banana, lemongrass, honey or sugar on acceptability of the resulting blends. Sensory evaluation ... Banana-flavoured blends resulted in phase separation that accounted for the relatively low acceptance. Soymilk ...

  20. Synchronization and suppression of chaos in non-locally coupled ...

    Indian Academy of Sciences (India)

    Abstract. We considered coupled map lattices with long-range interactions to study the spatiotemporal behaviour of spatially extended dynamical systems. Coupled map lattices have been intensively investigated as models to understand many spatiotemporal phenomena observed in extended system, and consequently ...

  1. Compton suppression gamma ray spectrometry

    International Nuclear Information System (INIS)

    Landsberger, S.; Iskander, F.Y.; Niset, M.; Heydorn, K.

    2002-01-01

    In the past decade there have been many studies to use Compton suppression methods in routine neutron activation analysis as well as in the traditional role of low level gamma ray counting of environmental samples. On a separate path there have been many new PC based software packages that have been developed to enhance photopeak fitting. Although the newer PC based algorithms have had significant improvements, they still suffer from being effectively used in weak gamma ray lines in natural samples or in neutron activated samples that have very high Compton backgrounds. We have completed a series of experiments to show the usefulness of Compton suppression. As well we have shown the pitfalls when using Compton suppression methods for high counting deadtimes as in the case of neutron activated samples. We have also investigated if counting statistics are the same both suppressed and normal modes. Results are presented in four separate experiments. (author)

  2. Thyroid suppression test with dextrothyroxine

    International Nuclear Information System (INIS)

    Rosenthal, D.; Fridman, J.; Ribeiro, H.B.

    1978-01-01

    The classic thyroid suppression test with triiodothyronine (l-T 3 ) has been shown to be efficient as an auxiliary method in the diagnosis of thyroid diseases, but should not be performed on elderly patients or on those with heart disease or a tendency to tachycardia. Since these subjects seem able to support a short period of dextro-thyronine (d-T 4 ) feeding, we compared the effect of d-T 4 and l-T 3 on the 24 hours thyroid uptake in euthyroid and hyperthyroid subjects. After basal radio-iodine uptake determination, 99 patients without hyperthyroidism and 27 with Graves' disease were randomly divided in 2 groups; one received 100μg of l-T 3 per day and the other 4 mg of d-T 4 per day, both groups being treated for a period of 10 days. At the end of this suppression period the 24 hours radio-iodine uptake was measured again and the percentual suppression index (S.I.) calculated. Since the comparison of the two groups showed no difference between the suppressive effect of l-T 3 and d-T 4 in euthyroid subjects, while dextro-thyronine, as levo-triiodothyronine, did not suppress the 24 hours uptake of hyperthyroid patients, l-T 3 or d-T 4 can be used interchangeably to test thyroid suppressibility. In the euthyroid subjects the normal range for the post-suppression uptake was 0-17.1% and for the suppression index 54,7.100% [pt

  3. Suppressed Charmed B Decay

    Energy Technology Data Exchange (ETDEWEB)

    Snoek, Hella Leonie [Vrije Univ., Amsterdam (Netherlands)

    2009-06-02

    This thesis describes the measurement of the branching fractions of the suppressed charmed B0 → D*- a0+ decays and the non-resonant B0 → D*- ηπ+ decays in approximately 230 million Υ(4S) → B$\\bar{B}$ events. The data have been collected with the BABAR detector at the PEP-II B factory at the Stanford Linear Accelerator Center in California. Theoretical predictions of the branching fraction of the B0 → D*- a{sub 0}+ decays show large QCD model dependent uncertainties. Non-factorizing terms, in the naive factorization model, that can be calculated by QCD factorizing models have a large impact on the branching fraction of these decay modes. The predictions of the branching fractions are of the order of 10-6. The measurement of the branching fraction gives more insight into the theoretical models. In general a better understanding of QCD models will be necessary to conduct weak interaction physics at the next level. The presence of CP violation in electroweak interactions allows the differentiation between matter and antimatter in the laws of physics. In the Standard Model, CP violation is incorporated in the CKM matrix that describes the weak interaction between quarks. Relations amongst the CKM matrix elements are used to present the two relevant parameters as the apex of a triangle (Unitarity Triangle) in a complex plane. The over-constraining of the CKM triangle by experimental measurements is an important test of the Standard Model. At this moment no stringent direct measurements of the CKM angle γ, one of the interior angles of the Unitarity Triangle, are available. The measurement of the angle γ can be performed using the decays of neutral B mesons. The B0 → D*- a0+ decay is sensitive to the angle γ and, in comparison to the current decays that are being employed, could significantly

  4. Localization of 131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy

    International Nuclear Information System (INIS)

    Larson, S.M.; Carrasquillo, J.A.; Krohn, K.A.

    1983-01-01

    33 patients with advanced malignant melanoma were studied after intravenous administration of 131 I-labeled Fab fragments specific for p97, an oncofetal glycoprotein of human melanoma. In all, 47 gamma camera imaging studies were performed for the purpose of localization of metastatic deposits. In addition to tumor, 131 I-Fab uptake was also seen in liver and kidney. 20 of these studies included simultaneous administration of both an 131 I-labeled Fab specific for p97, and an 125 I-labeled Fab not specific for p97. Blood clearance of p97-specific Fab was significantly more rapid than for nonspecific Fab. Eight of these patients had biopsies of subcutaneous nodules at 48 and 72 h postinjection in order to assess whether localization of radioactivity was antigen specific. Antigen-specific localization was observed with average ratios of specific/nonspecific uptake of 3.7 (48 h) and 3.4 (72 h); uptake was strongly correlated with tumor p97 concentration (r . 0.81, P less than 0.01). Also, imaging studies of the bio-distribution of 131 I-labeled anti-p97 Fab in patients selected for high p97 tumor concentration showed avid tumor uptake and more prolonged retention of labeled Fab in tumor than in normal tissues. Based on these studies, we estimated that total 131 I doses of 500 mCi could be safely given to patients before dose-limiting toxicity would be observed

  5. Beyond viral suppression of HIV

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V.; Safreed-Harmon, Kelly; Barton, Simon E

    2016-01-01

    BACKGROUND: In 2016, the World Health Organization (WHO) adopted a new Global Health Sector Strategy on HIV for 2016-2021. It establishes 15 ambitious targets, including the '90-90-90' target calling on health systems to reduce under-diagnosis of HIV, treat a greater number of those diagnosed......, and ensure that those being treated achieve viral suppression. DISCUSSION: The WHO strategy calls for person-centered chronic care for people living with HIV (PLHIV), implicitly acknowledging that viral suppression is not the ultimate goal of treatment. However, it stops short of providing an explicit target...... for health-related quality of life. It thus fails to take into account the needs of PLHIV who have achieved viral suppression but still must contend with other intense challenges such as serious non-communicable diseases, depression, anxiety, financial stress, and experiences of or apprehension about HIV...

  6. Aging and repeated thought suppression success.

    Directory of Open Access Journals (Sweden)

    Ann E Lambert

    Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

  7. Accentuation-suppression and scaling

    DEFF Research Database (Denmark)

    Sørensen, Thomas Alrik; Bundesen, Claus

    2012-01-01

    The limitations of the visual short-term memory (VSTM) system have become an increasingly popular field of study. One line of inquiry has focused on the way attention selects objects for encoding into VSTM. Using the framework of the Theory of Visual Attention (TVA; Bundesen, 1990 Psychological...... a scaling mechanism modulating the decision bias of the observer and also through an accentuation-suppression mechanism that modulates the degree of subjective relevance of objects, contracting attention around fewer, highly relevant objects while suppressing less relevant objects. These mechanisms may...

  8. Analysis of Tospovirus NSs Proteins in Suppression of Systemic Silencing.

    Science.gov (United States)

    Hedil, Marcio; Sterken, Mark G; de Ronde, Dryas; Lohuis, Dick; Kormelink, Richard

    2015-01-01

    RNA silencing is a sequence-specific gene regulation mechanism that in plants also acts antiviral. In order to counteract antiviral RNA silencing, viruses have evolved RNA silencing suppressors (RSS). In the case of tospoviruses, the non-structural NSs protein has been identified as the RSS. Although the tomato spotted wilt virus (TSWV) tospovirus NSs protein has been shown to exhibit affinity to long and small dsRNA molecules, its ability to suppress the non-cell autonomous part of RNA silencing has only been studied to a limited extent. Here, the NSs proteins of TSWV, groundnut ringspot virus (GRSV) and tomato yellow ring virus (TYRV), representatives for three distinct tospovirus species, have been studied on their ability and strength to suppress local and systemic silencing. A system has been developed to quantify suppression of GFP silencing in Nicotiana benthamiana 16C lines, to allow a comparison of relative RNA silencing suppressor strength. It is shown that NSs of all three tospoviruses are suppressors of local and systemic silencing. Unexpectedly, suppression of systemic RNA silencing by NSsTYRV was just as strong as those by NSsTSWV and NSsGRSV, even though NSsTYRV was expressed in lower amounts. Using the system established, a set of selected NSsTSWV gene constructs mutated in predicted RNA binding domains, as well as NSs from TSWV isolates 160 and 171 (resistance breakers of the Tsw resistance gene), were analyzed for their ability to suppress systemic GFP silencing. The results indicate another mode of RNA silencing suppression by NSs that acts further downstream the biogenesis of siRNAs and their sequestration. The findings are discussed in light of the affinity of NSs for small and long dsRNA, and recent mutant screen of NSsTSWV to map domains required for RSS activity and triggering of Tsw-governed resistance.

  9. Consequences of stereotype suppression and internal suppression motivation : A self-regulation approach

    NARCIS (Netherlands)

    Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.

    The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in

  10. Local food:

    DEFF Research Database (Denmark)

    Sundbo, Donna Isabella Caroline

    2013-01-01

    are identified and then categorised according to whether they pertain to the food product itself or the production methods and facilities and whether they describe physical or social properties of local food. From this a model with four categories is developed. It is found that properties of the product are more......Recently there has been more focus on food in general and local food in particular. But what is local food? And what are the perceptions of this concept according to theory and to providers and consumers of local food? This article first summarises and compares three different theoretical...... perspectives on local food, namely experience economy, local food systems and what is termed pro-industrialism. These have differing and sometimes opposite conceptualisations and aims for the concept of local food. Using the perspective of experience economy as theoretical background, the concept of local food...

  11. Local Content

    CSIR Research Space (South Africa)

    Gibberd, Jeremy

    2016-10-01

    Full Text Available Local content refers to materials and products made in a country as opposed those that are imported. There is an increasing interest in the concept of local content as a means of supporting local economies and providing jobs (Belderbos & Sleuwaegen...

  12. Suppression of stratified explosive interactions

    Energy Technology Data Exchange (ETDEWEB)

    Meeks, M.K.; Shamoun, B.I.; Bonazza, R.; Corradini, M.L. [Wisconsin Univ., Madison, WI (United States). Dept. of Nuclear Engineering and Engineering Physics

    1998-01-01

    Stratified Fuel-Coolant Interaction (FCI) experiments with Refrigerant-134a and water were performed in a large-scale system. Air was uniformly injected into the coolant pool to establish a pre-existing void which could suppress the explosion. Two competing effects due to the variation of the air flow rate seem to influence the intensity of the explosion in this geometrical configuration. At low flow rates, although the injected air increases the void fraction, the concurrent agitation and mixing increases the intensity of the interaction. At higher flow rates, the increase in void fraction tends to attenuate the propagated pressure wave generated by the explosion. Experimental results show a complete suppression of the vapor explosion at high rates of air injection, corresponding to an average void fraction of larger than 30%. (author)

  13. Strangeness Suppression and Color Deconfinement

    Science.gov (United States)

    Satz, Helmut

    2018-02-01

    The relative multiplicities for hadron production in different high energy collisions are in general well described by an ideal gas of all hadronic resonances, except that under certain conditions, strange particle rates are systematically reduced. We show that the suppression factor γs, accounting for reduced strange particle rates in pp, pA and AA collisions at different collision energies, becomes a universal function when expressed in terms of the initial entropy density s0 or the initial temperature T of the produced thermal medium. It is found that γs increases from about 0.5 to 1.0 in a narrow temperature range around the quark-hadron transition temperature Tc ≃ 160 MeV. Strangeness suppression thus disappears with the onset of color deconfinement; subsequently, full equilibrium resonance gas behavior is attained.

  14. Local conservation laws and the structure of the many-body localized states.

    Science.gov (United States)

    Serbyn, Maksym; Papić, Z; Abanin, Dmitry A

    2013-09-20

    We construct a complete set of local integrals of motion that characterize the many-body localized (MBL) phase. Our approach relies on the assumption that local perturbations act locally on the eigenstates in the MBL phase, which is supported by numerical simulations of the random-field XXZ spin chain. We describe the structure of the eigenstates in the MBL phase and discuss the implications of local conservation laws for its nonequilibrium quantum dynamics. We argue that the many-body localization can be used to protect coherence in the system by suppressing relaxation between eigenstates with different local integrals of motion.

  15. Chk1 suppressed cell death

    Directory of Open Access Journals (Sweden)

    Meuth Mark

    2010-09-01

    Full Text Available Abstract The role of Chk1 in the cellular response to DNA replication stress is well established. However recent work indicates a novel role for Chk1 in the suppression of apoptosis following the disruption of DNA replication or DNA damage. This review will consider these findings in the context of known pathways of Chk1 signalling and potential applications of therapies that target Chk1.

  16. In-Flight Suppressant Deployment Temperatures

    National Research Council Canada - National Science Library

    Bein, Donald

    2006-01-01

    .... An assessment is made of the model output versus some aircraft measurement data, fire suppressant boiling point criterion, as well as the history of altitude/temperature at which fire suppressants have been deployed...

  17. Fatal attraction? Intraguild facilitation and suppression among predators

    Science.gov (United States)

    Sivy, Kelly J.; Pozzanghera, Casey B.; Grace, James B.; Prugh, Laura R.

    2017-01-01

    Competition and suppression are recognized as dominant forces that structure predator communities. Facilitation via carrion provisioning, however, is a ubiquitous interaction among predators that could offset the strength of suppression. Understanding the relative importance of these positive and negative interactions is necessary to anticipate community-wide responses to apex predator declines and recoveries worldwide. Using state-sponsored wolf (Canis lupus) control in Alaska as a quasi experiment, we conducted snow track surveys of apex, meso-, and small predators to test for evidence of carnivore cascades (e.g., mesopredator release). We analyzed survey data using an integrative occupancy and structural equation modeling framework to quantify the strengths of hypothesized interaction pathways, and we evaluated fine-scale spatiotemporal responses of nonapex predators to wolf activity clusters identified from radio-collar data. Contrary to the carnivore cascade hypothesis, both meso- and small predator occupancy patterns indicated guild-wide, negative responses of nonapex predators to wolf abundance variations at the landscape scale. At the local scale, however, we observed a near guild-wide, positive response of nonapex predators to localized wolf activity. Local-scale association with apex predators due to scavenging could lead to landscape patterns of mesopredator suppression, suggesting a key link between occupancy patterns and the structure of predator communities at different spatial scales.

  18. Fatal Attraction? Intraguild Facilitation and Suppression among Predators.

    Science.gov (United States)

    Sivy, Kelly J; Pozzanghera, Casey B; Grace, James B; Prugh, Laura R

    2017-11-01

    Competition and suppression are recognized as dominant forces that structure predator communities. Facilitation via carrion provisioning, however, is a ubiquitous interaction among predators that could offset the strength of suppression. Understanding the relative importance of these positive and negative interactions is necessary to anticipate community-wide responses to apex predator declines and recoveries worldwide. Using state-sponsored wolf (Canis lupus) control in Alaska as a quasi experiment, we conducted snow track surveys of apex, meso-, and small predators to test for evidence of carnivore cascades (e.g., mesopredator release). We analyzed survey data using an integrative occupancy and structural equation modeling framework to quantify the strengths of hypothesized interaction pathways, and we evaluated fine-scale spatiotemporal responses of nonapex predators to wolf activity clusters identified from radio-collar data. Contrary to the carnivore cascade hypothesis, both meso- and small predator occupancy patterns indicated guild-wide, negative responses of nonapex predators to wolf abundance variations at the landscape scale. At the local scale, however, we observed a near guild-wide, positive response of nonapex predators to localized wolf activity. Local-scale association with apex predators due to scavenging could lead to landscape patterns of mesopredator suppression, suggesting a key link between occupancy patterns and the structure of predator communities at different spatial scales.

  19. In the suppression of regge cut contributions

    International Nuclear Information System (INIS)

    Chia, S.P.

    1975-07-01

    It is shown that contributions of reggeon-pomeron cuts are suppressed in amplitudes with opposite natural to the reggeon. This suppression grows logarithmically with energy. The suppression in the πP cut is, however, found to be weak. Consequence on conspiracy is discussed

  20. Polypyrrole Actuators for Tremor Suppression

    DEFF Research Database (Denmark)

    Skaarup, Steen; Mogensen, Naja; Bay, Lasse

    2003-01-01

    Neurological tremor affecting limbs can be divided into at least 6 different types with frequencies ranging from 2 to about 20 Hz. In order to alleviate the symptoms by suppressing the tremor, sensing and actuation systems able to perform at these frequencies are needed. Electroactive polymers...... exemplify 'soft actuator' technology that may be especially suitable for use in conjunction with human limbs. The electrochemical and mechanical properties of polypyrrole dodecyl benzene sulphonate actuator films have been studied with this application in mind. The results show that the time constants...

  1. Suppression effects on musical and verbal memory.

    Science.gov (United States)

    Schendel, Zachary A; Palmer, Caroline

    2007-06-01

    Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues.

  2. Pressure suppression pool thermal mixing

    International Nuclear Information System (INIS)

    Cook, D.H.

    1984-01-01

    A model is developed and verified to describe the thermal mixing that occurs in the pressure suppression pool (PSP) of a commercial BWR. The model is designed specifically for a Mark-I containment and is intended for use in severe accident sequence analyses. The model produces space and time dependent temperature results throughout the PSP and is useful for evaluating the bulk PSP thermal mixing, the condensation effectiveness of the PSP, and the long-term containment integrity. The model is designed to accommodate single or multiple discharging T-quenchers, a PSP circumferential circulation induced by the residual heat removal system discharge, and the thermal stratification of the pool that occurs immediately after the relief valves close. The PSP thermal mixing model is verified by comparing the model predicted temperatures to experimental temperatures that were measured in an operating BWR suppression pool. The model is then used to investigate several PSP thermal mixing problems that include the time to saturate at full relief valve flow, the temperature response to a typical stuck open relief valve scenario, and the effect of operator rotation of the relief valve discharge point

  3. Localized superconductors

    International Nuclear Information System (INIS)

    Ma, M.; Lee, P.A.

    1985-01-01

    We study the effects of Anderson localization on superconductivity by using a Bardeen-Cooper-Schrieffer (BCS)-type trial wave function which pairs electrons in exact time-reversed eigenstates of the single-particle Hamiltonian. Within this approximation, and neglecting localization effects on the effective Coulomb repulsion and the electron-phonon coupling, we find that superconductivity persists below the mobility edge. In fact, Anderson's theorem is valid in the localized phase as long as rhoΔ 0 L/sup d/ > 1 (rho is the density of states averaged over +- Δ 0 of the Fermi energy, Δ 0 the BCS gap parameter, and L the localization length). Hence the gap order parameter Δ(r) remains uniform in space at the BCS value Δ 0 . The superfluid density and response to electromagnetic perturbations, however, show marked differences from the ''dirty superconductor'' regime. For rhoΔ 0 L/sup d/ < 1, Δ(r) fluctuates spatially and eventually drops to zero. In the limit when states are site localized, the system crosses over into the ''Anderson negative-U glass.'' Considerations beyond the trial wave-function approximation will speed up the destruction of superconductivity. The superconductor formed from localized states has the property that its quasiparticle excitations are also localized. Such excitations can be probed by observing the normal current in a tunneling junction

  4. An approach to the unification of suppressor T cell circuits: a simplified assay for the induction of suppression by T cell-derived, antigen-binding molecules (T-ABM).

    Science.gov (United States)

    Chue, B; Ferguson, T A; Beaman, K D; Rosenman, S J; Cone, R E; Flood, P M; Green, D R

    1989-01-01

    A system is presented in which the in vitro response to sheep red blood cells (SRBC) can be regulated using antigenic determinants coupled to SRBC and T cell-derived antigen-binding molecules (T-ABM) directed against the coupled determinants. T suppressor-inducer factors (TsiF's) are composed of two molecules, one of which is a T-ABM and one which bears I-J determinants (I-J+ molecule). Using two purified T-ABM which have not previously been shown to have in vitro activity, we produced antigen-specific TsiF's which were capable of inducing the suppression of the anti-SRBC response. Suppression was found to require both the T-ABM and the I-J+ molecule, SRBC conjugated with the antigen for which the T-ABM was specific, and a population of Ly-2+ T cells in the culture. Two monoclonal TsiF (or TsF1) were demonstrated to induce suppression of the anti-SRBC response in this system, provided the relevant antigen was coupled to the SRBC in culture. The results are discussed in terms of the general functions of T-ABM in the immune system. This model will be useful in direct, experimental comparisons of the function of T-ABM and suppressor T cell factors under study in different systems and laboratories.

  5. The role of suppression in amblyopia.

    Science.gov (United States)

    Li, Jingrong; Thompson, Benjamin; Lam, Carly S Y; Deng, Daming; Chan, Lily Y L; Maehara, Goro; Woo, George C; Yu, Minbin; Hess, Robert F

    2011-06-13

    This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

  6. Localized Scleroderma

    Science.gov (United States)

    ... How Is Localized Scleroderma Diagnosed? Doctors who are familiar with scleroderma, or who are experts at examining ... systemic treatment with a medication or other treatment interventions (for example, ultraviolet light), are reserved for more ...

  7. Local orbit feedback

    International Nuclear Information System (INIS)

    Anon.

    1991-01-01

    Critically aligned experiments are sensitive to small changes in the electron beam orbit. At the NSLS storage rings, the electron beam and photon beam motions have been monitored over the past several years. In the survey conducted in 1986 by the NSLS Users Executive Committee, experimenters requested the vertical beam position variation and the vertical angle variation, within a given fill, remain within 10 μm and 10 μr, respectively. This requires improvement in the beam stability by about one order of magnitude. At the NSLS and SSRL storage rings, the beam that is originally centered on the position monitor by a dc orbit correction is observed to have two kinds of motion: a dc drift over a storage period of several hours and a beam bounce about its nominal position. These motions are a result of the equilibrium orbit not being held perfectly stable due to time-varying errors introduced into the magnetic guide field by power supplies, mechanical vibration of the magnets, cooling water temperature variations, etc. The approach to orbit stabilization includes (1) identifying and suppressing as many noise sources on the machine as possible, (2) correcting the beam position globally (see Section 6) by controlling a number of correctors around the circumference of the machine, and (3) correcting the beam position and angle at a given source location by position feedback using local detectors and local orbit bumps. The third approach, called Local Orbit Feedback will be discussed in this section

  8. A saponin-detoxifying enzyme mediates suppression of plant defences

    Science.gov (United States)

    Bouarab, K.; Melton, R.; Peart, J.; Baulcombe, D.; Osbourn, A.

    2002-08-01

    Plant disease resistance can be conferred by constitutive features such as structural barriers or preformed antimicrobial secondary metabolites. Additional defence mechanisms are activated in response to pathogen attack and include localized cell death (the hypersensitive response). Pathogens use different strategies to counter constitutive and induced plant defences, including degradation of preformed antimicrobial compounds and the production of molecules that suppress induced plant defences. Here we present evidence for a two-component process in which a fungal pathogen subverts the preformed antimicrobial compounds of its host and uses them to interfere with induced defence responses. Antimicrobial saponins are first hydrolysed by a fungal saponin-detoxifying enzyme. The degradation product of this hydrolysis then suppresses induced defence responses by interfering with fundamental signal transduction processes leading to disease resistance.

  9. Safety system for pressure suppression

    International Nuclear Information System (INIS)

    Wood, L.E.; Ludwig, G.J.; Tulsa, O.

    1975-01-01

    The rupture disk with rated breaking points is constrained by two supporting elements and has a convex-concave shape. For pressure suppression, it is reversable inversely to its bulging. Its surface has notches which are the rated breaking points and respond to higher pressures. The centre of the rupture disk contains an area of relatively smaller thickness that will burst at lower pressure and thus makes it applicable for lower pressures. For the response of the rupture disk centre, a thrust ring with a central opening may also be used. Its edge is formed into a convex-concave section supported on the edge of the rupture disk on the exit side. The free centre of the rupture disk is then the area of relative weakness. (RW/AK) [de

  10. MEK5 suppresses osteoblastic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Kaneshiro, Shoichi [Department of Orthopaedic Surgery, Japan Community Health Care Organization Osaka Hospital, 4-2-78 Fukushima, Fukushima Ward, Osaka City, Osaka 553-0003 (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Higuchi, Chikahisa, E-mail: c-higuchi@umin.ac.jp [Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  11. Charmonium formation and suppression in nuclear matter

    International Nuclear Information System (INIS)

    Xu Jiajun; Wang Jia; Zhuang Chao; Zhuang Pengfei

    2005-01-01

    The coupling Schroedinger equations describing the evolution of cc-bar states in nuclear matter are analytically and systematically solved via perturbation method, and the correlation between charmonium formation and nuclear absorption is investigated. After calculating J/Ψ and Ψ' suppression in nucleon-nucleus collisions and comparing with experiment data, it is found that the formation time effect plays an important rule in charmonium suppression, especially in Ψ' suppression. (authors)

  12. Quantum-classical correspondence in multimensional nonlinear systems: Anderson localization and "superdiffusive" solitons

    KAUST Repository

    Brambila, Danilo; Fratalocchi, Andrea

    2012-01-01

    We have theoretically studied Anderson localization in a 2D+1 nonlinear kicked rotor model. The system shows a very rich dynamical behavior, where the Anderson localization is suppressed and soliton wave-particles undergo a superdiffusive motion.

  13. Deconstructing Interocular Suppression: Attention and Divisive Normalization.

    Directory of Open Access Journals (Sweden)

    Hsin-Hung Li

    2015-10-01

    Full Text Available In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression, the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature and divisive normalization contribute to interocular suppression.

  14. Deconstructing Interocular Suppression: Attention and Divisive Normalization.

    Science.gov (United States)

    Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

    2015-10-01

    In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

  15. Locals Collection

    Directory of Open Access Journals (Sweden)

    Stephen Hastings-King

    2010-03-01

    Full Text Available A locals collection is a set of parameters that are used to delimit data-mining operations. This piece uses a collection of locals from around Essex Massachusetts to shape and delimit an interrogation of post-reality in contemporary America. It explores the notion of crisis, the possibility of a crisis of empire that may or may not emerge in a media-space that does not allow crisis of empire to be mentioned and relations this maybe-crisis to the various levels of economic dysfunction that have become evident since late 2008. But mostly this piece explores ways in which particular stories about particular people do and do not link/link to these larger-scale narratives. This is the first of a potential series of locals collections that will mine the American post-real.

  16. Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T Cell Mediated Tumor Control in the Genital Tract

    Science.gov (United States)

    Sun, Yun-Yan; Peng, Shiwen; Han, Liping; Qiu, Jin; Song, Liwen; Tsai, Yachea; Yang, Benjamin; Roden, Richard B.S.; Trimble, Cornelia L.; Hung, Chien-Fu; Wu, T-C

    2015-01-01

    Purpose Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Experimental Design Here we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than IM delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16+ cervical cancer (TC-1 luc). Results We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8+ T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8+ T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8+ T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8+ T cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Conclusions Our results support future clinical translation using cervicovaginal TA-HPV vaccination. PMID:26420854

  17. Anderson localization of light near boundaries of disordered photonic lattices

    International Nuclear Information System (INIS)

    Jovic, Dragana M.; Kivshar, Yuri S.; Denz, Cornelia; Belic, Milivoj R.

    2011-01-01

    We study numerically the effect of boundaries on Anderson localization of light in truncated two-dimensional photonic lattices in a nonlinear medium. We demonstrate suppression of Anderson localization at the edges and corners, so that stronger disorder is needed near the boundaries to obtain the same localization as in the bulk. We find that the level of suppression depends on the location in the lattice (edge vs corner), as well as on the strength of disorder. We also discuss the effect of nonlinearity on various regimes of Anderson localization.

  18. NF-κB RelA renders tumor-associated macrophages resistant to and capable of directly suppressing CD8+ T cells for tumor promotion.

    Science.gov (United States)

    Li, Liwen; Han, Lei; Sun, Fan; Zhou, Jingjiao; Ohaegbulam, Kim C; Tang, Xudong; Zang, Xingxing; Steinbrecher, Kris A; Qu, Zhaoxia; Xiao, Gutian

    2018-01-01

    Activation of the inflammatory transcription factor NF-κB in tumor-associated macrophages (TAMs) is assumed to contribute to tumor promotion. However, whether and how NF-κB drives the antitumor macrophages to become pro-tumorigenic have not been determined in any cancer type yet. Similarly, how TAMs repress CD8 + cytotoxic T lymphocytes (CTLs) remains largely unknown, although their importance in regulatory T (Treg) cell regulation and tumor promotion has been well appreciated. Here, using an endogenous lung cancer model we uncover a direct crosstalk between TAMs and CTLs. TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner. Remarkably, TAMs secrete the known T-cell suppressive cytokine interleukin-10 (IL-10) to activate, but not to repress, CTLs. Notably, one major role of cell-intrinsic NF-κB RelA is to drive TAMs to suppress CTLs for tumor promotion. It induces B7x expression in TAMs directly, and restricts IL-10 expression indirectly by repressing expression of the NF-κB cofactor Bcl3 and subsequent Bcl3/NF-κB1-mediated transcription of IL-10. It also renders TAMs resistant to CTLs by up-regulating anti-apoptotic genes. These studies help understand how immunity is shaped in lung tumorigenesis, and suggest a RelA-targeted immunotherapy for this deadliest cancer.

  19. Suppressing magnetic island growth by resonant magnetic perturbation

    Science.gov (United States)

    Yu, Q.; Günter, S.; Lackner, K.

    2018-05-01

    The effect of externally applied resonant magnetic perturbations (RMPs) on the growth of magnetic islands is investigated based on two-fluid equations. It is found that if the local bi-normal electron fluid velocity at the resonant surface is sufficiently large, static RMPs of the same helicity and of moderate amplitude can suppress the growth of magnetic islands in high-temperature plasmas. These islands will otherwise grow, driven by an unfavorable plasma current density profile and bootstrap current perturbation. These results indicate that the error field can stabilize island growth, if the error field amplitude is not too large and the local bi-normal electron fluid velocity is not too low. They also indicate that applied rotating RMPs with an appropriate frequency can be utilized to suppress island growth in high-temperature plasmas, even for a low bi-normal electron fluid velocity. A significant change in the local equilibrium plasma current density gradient by small amplitude RMPs is found for realistic plasma parameters, which are important for the island stability and are expected to be more important for fusion reactors with low plasma resistivity.

  20. Local equilibrium

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1984-12-15

    From 3-6 September the First International Workshop on Local Equilibrium in Strong Interaction Physics took place in Bad-Honnef at the Physics Centre of the German Physical Society. A number of talks covered the experimental and theoretical investigation of the 'hotspots' effect, both in high energy particle physics and in intermediate energy nuclear physics.

  1. Overcompensation of herbivore reproduction through hyper-suppression of plant defenses in response to competition.

    Science.gov (United States)

    Schimmel, Bernardus C J; Ataide, Livia M S; Chafi, Rachid; Villarroel, Carlos A; Alba, Juan M; Schuurink, Robert C; Kant, Merijn R

    2017-06-01

    Spider mites are destructive arthropod pests on many crops. The generalist herbivorous mite Tetranychus urticae induces defenses in tomato (Solanum lycopersicum) and this constrains its fitness. By contrast, the Solanaceae-specialist Tetranychus evansi maintains a high reproductive performance by suppressing tomato defenses. Tetranychus evansi outcompetes T. urticae when infesting the same plant, but it is unknown whether this is facilitated by the defenses of the plant. We assessed the extent to which a secondary infestation by a competitor affects local plant defense responses (phytohormones and defense genes), mite gene expression and mite performance. We observed that T. evansi switches to hyper-suppression of defenses after its tomato host is also invaded by its natural competitor T. urticae. Jasmonate (JA) and salicylate (SA) defenses were suppressed more strongly, albeit only locally at the feeding site of T. evansi, upon introduction of T. urticae to the infested leaflet. The hyper-suppression of defenses coincided with increased expression of T. evansi genes coding for salivary defense-suppressing effector proteins and was paralleled by an increased reproductive performance. Together, these observations suggest that T. evansi overcompensates its reproduction through hyper-suppression of plant defenses in response to nearby competitors. We hypothesize that the competitor-induced overcompensation promotes competitive population growth of T. evansi on tomato. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  2. Net Locality

    DEFF Research Database (Denmark)

    de Souza e Silva, Adriana Araujo; Gordon, Eric

    Provides an introduction to the new theory of Net Locality and the profound effect on individuals and societies when everything is located or locatable. Describes net locality as an emerging form of location awareness central to all aspects of digital media, from mobile phones, to Google Maps......, to location-based social networks and games, such as Foursquare and facebook. Warns of the threats these technologies, such as data surveillance, present to our sense of privacy, while also outlining the opportunities for pro-social developments. Provides a theory of the web in the context of the history...... of emerging technologies, from GeoCities to GPS, Wi-Fi, Wiki Me, and Google Android....

  3. Local supertwistors

    International Nuclear Information System (INIS)

    Merkulov, S.A.

    1987-01-01

    Geometry of local supertwistors is investigated. It is proved that the Yang-Mills equations for the introduced ansatz for supertwistor connection are equivalent to free bach equations, describing the dynamics of N=1 conformal supergravity. Analogous interpretation of the dynamics of N=1 conformal supergravity coupled to a vector superfield is proposed. It is proved that any complex conformally right or left flat superspace automatically satisfies the Bach equations

  4. T1 pseudohyperintensity on fat-suppressed MRI: A potential diagnostic pitfall

    Science.gov (United States)

    Huynh, Tuan N.; Johnson, D. Thor; Poder, Liina; Joe, Bonnie N.; Webb, Emily M.; Coakley, Fergus V.

    2011-01-01

    MRI findings in two patients with misleading T1 hyperintensity seen only on fat-suppressed images are presented, one with a renal cell carcinoma that was misinterpreted as a hemorrhagic cyst and the other with an ovarian serous cystadenocarcinoma that was misinterpreted as a complicated endometrioma. The apparent T1 hyperintensity on fat suppressed images in these cases was likely due to varying perception of image signal dependent on local contrast, an optical effect known as the checker-shadow illusion. T1 pseudohyperintensity should be considered when apparently high T1 signal intensity is seen only on fat-suppressed images; review of non fat-suppressed images may help prevent an erroneous diagnoses of blood-containing lesions. PMID:21765301

  5. Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

    Science.gov (United States)

    Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

    2013-10-01

    Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

  6. Psychopathology and Thought Suppression: A Quantitative Review

    Science.gov (United States)

    Magee, Joshua C.; Harden, K. Paige; Teachman, Bethany A.

    2012-01-01

    Recent theories of psychopathology have suggested that thought suppression intensifies the persistence of intrusive thoughts, and proposed that difficulty with thought suppression may differ between groups with and without psychopathology. The current meta-analytic review evaluates empirical evidence for difficulty with thought suppression as a function of the presence and specific type of psychopathology. Based on theoretical proposals from the psychopathology literature, diagnosed and analogue samples were expected to show greater recurrence of intrusive thoughts during thought suppression attempts than non-clinical samples. However, results showed no overall differences in the recurrence of thoughts due to thought suppression between groups with and without psychopathology. There was, nevertheless, variation in the recurrence of thoughts across different forms of psychopathology, including relatively less recurrence during thought suppression for samples with symptoms of Obsessive-Compulsive Disorder, compared to non-clinical samples. However, these differences were typically small and provided only mixed support for existing theories. Implications for cognitive theories of intrusive thoughts are discussed, including proposed mechanisms underlying thought suppression. PMID:22388007

  7. Volatile suppressing method for radioactive iodine

    International Nuclear Information System (INIS)

    Ohara, Atsushi; Haruguchi, Keiko.

    1997-01-01

    In the present invention, a metal plate is disposed above the pool water surface of a suppression chamber disposed to a reactor container in order to reduce evaporation of radioactive iodine released from a suppression pool. A metal plate is disposed above the pool water surface of the suppression chamber disposed to the reactor container. In addition, a metal plate is disposed around the space connecting a bent tube extending from a dry well to underwater of suppression pool water and a gas bent tube extending from the suppression chamber to an emergency gas processing system. Spray water is supplied for cooling the suppression chamber d as a means for cooling the metal plate. Then, among iodine released to the suppression chamber, elemental iodine liberated from the pool water is deposited on the surface of the metal plate, and the amount of iodine to be flown into and processed by an emergency gas processing system or a filter bent system can be reduced. (T.M.)

  8. Lumican alleviates hypertrophic scarring by suppressing integrin-FAK signaling

    International Nuclear Information System (INIS)

    Zhao, Yuqian; Li, Xueyong; Xu, Xiaoli; He, Zhi; Cui, Lei; Lv, Xiaoxing

    2016-01-01

    Hypertrophic scarring (HS) is an overcompensation of wound healing that increases the risk of cosmetic disfigurement and functional impairment. No gold standard has been established for the treatment or prevention of HS. Our study aims to elucidate the expression and function of lumican in the pathogenesis of HS as well as the underlying mechanism involved in this procedure. An animal model of HS (rabbit ear) was established, and the Ad-lumican vectors were locally injected. Primary fibroblasts isolated from patients with hypertrophic burn scars were used in vitro. Histological and molecular changes in HS pathogenesis were evaluated. The results showed that lumican is significantly reduced in HS tissues and fibroblasts from HS patients as compared to normal skin or cells. Lumican levels were further suppressed in response to TGF-β stimulation. However, lumican upregulation effectively thinned the scar area and inhibited fibroblast proliferation and the cell cycle. Meanwhile, Ad-lumican administration suppressed the deposition of extracellular matrix, such as collagen and CTGF. Ad-lumican injected animals or fibroblasts presented comparable integrin α 2 β 1 expression while greatly reduced phosphorylation of FAK compared to the negative control. Moreover, Ad-lumican administration largely enhanced the binding of lumican to integrin α 2 β 1 and may thus inhibit the signaling propagation of collagen-integrin α 2 β 1 . Overall, the restoration of lumican levels contributed to suppressing the HS progression by inhibiting collagen-integrin α 2 β 1 -FAK signaling. - Highlights: • Lumican is downregulated during hypertrophic scar formation. • Lumican inhibits fibroblast proliferation. • Lumican inhibits extracellular matrix deposition. • Lumican suppresses collagen-integrin-FAK signaling.

  9. Regional Extent of Peripheral Suppression in Amblyopia.

    Science.gov (United States)

    Babu, Raiju J; Clavagnier, Simon; Bobier, William R; Thompson, Benjamin; Hess, Robert F

    2017-04-01

    Previously, we have mapped amblyopic eye suppression within the central 20° of the visual field and observed a gradient of suppression that is strongest in central vision and weakens with increasing eccentricity. In this study, using a large dichoptic display, we extend our novel suppression mapping approach further into the periphery (from 20°-60°) to assess whether suppression continues to decline with eccentricity or plateaus. Sixteen participants with amblyopia (10 with strabismus, 6 with anisometropia without strabismus; mean age: 37.9 ± 11 years) and six normal observers (mean age: 28.3 ± 5 years) took part. The visual stimulus (60° diameter), viewed from 57 cm, was composed of four concentric annuli (5° radius) with alternate contrast polarities starting from an eccentricity of 10°. Each annulus was divided into eight sectors subtending 45° of visual angle. Participants adjusted the contrast of a single sector presented to the fellow eye to match the perceived contrast of the remaining stimulus elements that were presented to the amblyopic eye. A matching contrast that was lower in the fellow eye than the amblyopic eye indicated suppression. Patients with strabismus exhibited significantly stronger interocular suppression than controls across all eccentricities (P = 0.01). Patients with anisometropia did not differ from controls (P = 0.58). Suppression varied significantly with eccentricity (P = 0.005) but this effect did not differ between patient groups (P = 0.217). In amblyopia, suppression is present beyond the central 10° in patients with strabismus. Suppression becomes weaker at greater eccentricities and this may enable peripheral fusion that could be used by binocular treatment methods.

  10. Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

    Science.gov (United States)

    Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

    2017-12-01

    Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key

  11. Age-related decline in global form suppression

    DEFF Research Database (Denmark)

    Wiegand, Iris Michaela; Finke, Kathrin; Töllner, Thomas

    2015-01-01

    . Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global...... differences in the subsequent (250–500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanisza, as compared to non-Kanisza, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative...... to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages – indicative of older observers having difficulties with disengaging from a global default selection mode...

  12. Local supertwistors

    International Nuclear Information System (INIS)

    Merkulov, S.A.

    1987-01-01

    The geometry of local supertwistors is investigated. An ansatz on the form of the supertwistor superconnection is introduced. Because of this restriction on the form of such a superconnection the Yang-Mills equations for the superconnection turn out to be equivalent to the free Bach equations describing the dynamics of simple conformal supergravity. It is shown that the equations of motion of conformal supergravity interacting with a vector superfield admit an analogous interpretation. It is proved that an arbitrary conformally right-flat or left-flat superspace is automatically a solution of the Bach equations

  13. Low-dose oral tolerance due to antigen in the diet suppresses differentially the cholera toxin-adjuvantized IgE, IgA and IgG response

    DEFF Research Database (Denmark)

    Christensen, Hanne Risager; Kjær, Tanja; Frøkiær, Hanne

    2003-01-01

    Background: Cholera toxin (CT) is used as a mucosal adjuvant amongst other applications for studying food allergy because oral administration of antigen with CT induces an antigen-specific type 2 response, including IgE and IgA production. Priorly established oral tolerance due to antigen...... soy-trypsin inhibitor (KSTI) (F0 mice) and mice fed a soy-free diet (F2 mice) were orally immunized with KSTI and CT. KSTI-specific serum IgG1, IgG2a, IgA and IgE and fecal IgA were monitored. KSTI-stimulated cell proliferation and interleukin (IL)-6 production were determined. Results: The anti...... immunizations. However, cell proliferation and IL-6 production were clearly suppressed even after five immunizations. Conclusions: Priorly established low-dose oral tolerance considerably suppressed the CT-adjuvantized KSTI-specific IgE, IgA and cellular immune response but only weakly and transiently the Ig...

  14. Chondromalacia patellae: fat-suppressed MR imaging.

    Science.gov (United States)

    Rose, P M; Demlow, T A; Szumowski, J; Quinn, S F

    1994-11-01

    To evaluate the accuracy of fat-suppressed magnetic resonance (MR) imaging in diagnosing chondromalacia patellae. Seventy-one patients underwent fat-suppressed MR imaging and arthroscopy of the patellofemoral compartment. Findings were classified as early or advanced chondromalacia or as normal and were correlated with arthroscopic findings. Early and advanced stages of chondromalacia patellae were reliably detected, with positive predictive values of 85% and 92%, respectively. Specificity in early stages was 94% and in late stages was 98%. However, the overall accuracies did not differ substantially from those reported in studies that did not use fat-suppressed imaging. Axial, fat-suppressed MR imaging accurately depicts changes caused by chondromalacia patellae. Early stages can be seen as intrasubstance changes of increased signal intensity. Results of this study suggest a high degree of specificity in excluding both early and advanced changes.

  15. METHOD OF SUPPRESSING GASTROINTESTINAL UREASE ACTIVITY

    Science.gov (United States)

    Visek, W.J.

    1963-04-23

    This patent shows a method of increasing the growth rate of chicks. Certain diacyl substituted ureas such as alloxan, murexide, and barbituric acid are added to their feed, thereby suppressing gastrointestinal urease activity and thus promoting growth. (AEC)

  16. Suppression factors in diffractive photoproduction of dijets

    International Nuclear Information System (INIS)

    Klasen, Michael; Kramer, Gustav

    2010-06-01

    After new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut. (orig.)

  17. Attention modulates sensory suppression during back movements.

    Science.gov (United States)

    Van Hulle, Lore; Juravle, Georgiana; Spence, Charles; Crombez, Geert; Van Damme, Stefaan

    2013-06-01

    Tactile perception is often impaired during movement. The present study investigated whether such sensory suppression also occurs during back movements, and whether this would be modulated by attention. In two tactile detection experiments, participants simultaneously engaged in a movement task, in which they executed a back-bending movement, and a perceptual task, consisting of the detection of subtle tactile stimuli administered to their upper or lower back. The focus of participants' attention was manipulated by raising the probability that one of the back locations would be stimulated. The results revealed that tactile detection was suppressed during the execution of the back movements. Furthermore, the results of Experiment 2 revealed that when the stimulus was always presented to the attended location, tactile suppression was substantially reduced, suggesting that sensory suppression can be modulated by top-down attentional processes. The potential of this paradigm for studying tactile information processing in clinical populations is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Suppression of instability in rotatory hydromagnetic convection

    Indian Academy of Sciences (India)

    first time by Lord Rayleigh [9] for the idealized case of two free boundaries. Rayleigh's theory shows that the gravity-dominated thermal instability in liquid layer ... suppressed for oscillatory perturbations by the simultaneous application of a ...

  19. Combustion suppressing device for leaked sodium

    International Nuclear Information System (INIS)

    Ooto, Akihiro.

    1985-01-01

    Purpose: To suppress the atmospheric temperature to secure the building safety and shorten the recovery time after the leakage in a chamber for containing sodium leaked from coolant circuit equipments or pipeways of LMFBR type rector by suppressing the combustion of sodium contained in the chamber. Constitution: To the inner wall of a chamber for containing sodium handling equipments, are vertically disposed a panel having a coolant supply port at the upper portion and a coolant discharge port at the lower portion thereof and defined with a coolant flowing channel and a panel for sucking the coolant discharged from the abovementioned panel and exhausting the same externally. Further, a corrugated combustion suppressing plate having apertures for draining the condensated leaked sodium is disposed near the sodium handling equipments. If ruptures are resulted to the sodium handling equipments or pipeway, leaked sodium is passed through the drain apertures in the suppressing plate and stored at the bottom of the containing chamber. (Horiuchi, T.)

  20. Epithelium Expressing the E7 Oncoprotein of HPV16 Attracts Immune-Modulatory Dendritic Cells to the Skin and Suppresses Their Antigen-Processing Capacity.

    Directory of Open Access Journals (Sweden)

    Janin Chandra

    Full Text Available Antigen presenting cells (APCs in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs.

  1. Suppressing Tsetse Flies to Improve Lives

    International Nuclear Information System (INIS)

    Potterton, Louise; Pavlicek, Petr; Parker, Andrew

    2013-01-01

    In 2009, the government-run Southern Tsetse Eradication Project (STEP) in Ethiopia, with the support of the IAEA, started to carry out intensive activities to suppress the fly population using insecticides. The fly population is now down by 90%. The benefits of tsetse suppression can be seen all over the region. Diary produce is now widely available at markets and healthy animals can be seen everywhere in farming and transport

  2. Gamma camera scatter suppression unit WAM

    International Nuclear Information System (INIS)

    Kishi, Haruo; Shibahara, Noriyuki; Hirose, Yoshiharu; Shimonishi, Yoshihiro; Oumura, Masahiro; Ikeda, Hozumi; Hamada, Kunio; Ochi, Hironobu; Itagane, Hiroshi.

    1990-01-01

    In gamma camera imaging, scattered radiation is one of big factors to decrease image contrast. Simply, scatter suppression makes signal to noise ratio larger, but it makes statistics error because of radionuclide injection limit to the human body. EWA is a new method that suppresses scattered radiation and improves image contrast. In this article, WAM which is commercialized EWA method by Siemens Gammasonics Inc. is presented. (author)

  3. Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

    Science.gov (United States)

    Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

    2012-06-01

    What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

  4. Exogenous regucalcin suppresses the growth of human liver cancer HepG2 cells in vitro.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Murata, Tomiyasu

    2018-04-05

    Regucalcin, which its gene is localized on the X chromosome, plays a pivotal role as a suppressor protein in signal transduction in various types of cells and tissues. Regucalcin gene expression has been demonstrated to be suppressed in various tumor tissues of animal and human subjects, suggesting a potential role of regucalcin in carcinogenesis. Regucalcin, which is produced from the tissues including liver, is found to be present in the serum of human subjects and animals. This study was undertaken to determine the effects of exogenous regucalcin on the proliferation in cloned human hepatoma HepG2 cells in vitro. Proliferation of HepG2 cells was suppressed after culture with addition of regucalcin (0.01 – 10 nM) into culture medium. Exogenous regucalcin did not reveal apoptotic cell death in HepG2 cells in vitro. Suppressive effects of regucalcin on cell proliferation were not enhanced in the presence of various signaling inhibitors including tumor necrosis factor-α (TNF-α), Bay K 8644, PD98059, staurosporine, worthomannin, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) or gemcitabine, which were found to suppress the proliferation. In addition, exogenous regucalcin suppressed the formation of colonies of cultured hepatoma cells in vitro. These findings demonstrated that exogenous regucalcin exhibits a suppressive effect on the growth of human hepatoma HepG2 cells, proposing a strategy with the gene therapy for cancer treatment.

  5. Regulatory CD8{sup +} T cells induced by exposure to all-trans retinoic acid and TGF-{beta} suppress autoimmune diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Minoru [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Yasuda, Hisafumi, E-mail: yasuda@med.kobe-u.ac.jp [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Abe, Yasuhisa; Sasaki, Hirotomo; Shimizu, Mami; Arai, Takashi; Okumachi, Yasuyo; Moriyama, Hiroaki; Hara, Kenta; Yokono, Koichi; Nagata, Masao [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-03-26

    Antigen-specific regulatory CD4{sup +} T cells have been described but there are few reports on regulatory CD8{sup +} T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8{sup +} T cells from 8.3-NOD transgenic mice. CD8{sup +} T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-{beta}, and all-trans retinoic acid (ATRA) for 5 days. CD8{sup +} T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-{beta} and ATRA had low Foxp3{sup +} expression (1.7 {+-} 0.9% and 3.2 {+-} 4.5%, respectively). In contrast, CD8{sup +} T cells induced by exposure to IGRP, SpDCs, TGF-{beta}, and ATRA showed the highest expression of Foxp3{sup +} in IGRP-reactive CD8{sup +} T cells (36.1 {+-} 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8{sup +} T cells cultured with IGRP, SpDCs, TGF-{beta}, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8{sup +} T cells suppressed the proliferation of diabetogenic CD8{sup +} T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-{beta} induces CD8{sup +}Foxp3{sup +} T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

  6. Local Sustainability

    International Nuclear Information System (INIS)

    Carrizosa Umana, Julio

    1998-01-01

    The current polemic about the possibilities of sustainable development has led to a renovated interest for the topic of the sustainability of the communities and the local sustainability. In front of the global sustainability whose conditions have been exposed by systemic ecologists and for macro economists, the sustainability of specific places arises in the planet whose conditions are object of study of the ecology of landscapes, of the ecological economy, of the cultural anthropology, of the environmental sociology and naturally, of the integral environmentalism. In this discussion the Colombian case charges unusual interest to be one of the few countries of Latin America, where a very dense net of municipalities exists, each one with its urban helmet and with a position and some functions defined by the political constitution of the nation. This net of municipalities and of urban helmets it also constitutes net of alternative to the current macro-cephalic situation. As well as Bogota grew, in a hundred years, of less than a hundred thousand inhabitants to six million inhabitants, each one of these municipalities contains a potential of growth that depends on the characteristics of its ecological, social, economic and politic sustainability

  7. A compact clinical instrument for quantifying suppression.

    Science.gov (United States)

    Black, Joanne M; Thompson, Benjamin; Maehara, Goro; Hess, Robert F

    2011-02-01

    We describe a compact and convenient clinical apparatus for the measurement of suppression based on a previously reported laboratory-based approach. In addition, we report and validate a novel, rapid psychophysical method for measuring suppression using this apparatus, which makes the technique more applicable to clinical practice. By using a Z800 dual pro head-mounted display driven by a MAC laptop, we provide dichoptic stimulation. Global motion stimuli composed of arrays of moving dots are presented to each eye. One set of dots move in a coherent direction (termed signal) whereas another set of dots move in a random direction (termed noise). To quantify performance, we measure the signal/noise ratio corresponding to a direction-discrimination threshold. Suppression is quantified by assessing the extent to which it matters which eye sees the signal and which eye sees the noise. A space-saving, head-mounted display using current video technology offers an ideal solution for clinical practice. In addition, our optimized psychophysical method provided results that were in agreement with those produced using the original technique. We made measures of suppression on a group of nine adult amblyopic participants using this apparatus with both the original and new psychophysical paradigms. All participants had measurable suppression ranging from mild to severe. The two different psychophysical methods gave a strong correlation for the strength of suppression (rho = -0.83, p = 0.006). Combining the new apparatus and new psychophysical method creates a convenient and rapid technique for parametric measurement of interocular suppression. In addition, this apparatus constitutes the ideal platform for suppressors to combine information between their eyes in a similar way to binocularly normal people. This provides a convenient way for clinicians to implement the newly proposed binocular treatment of amblyopia that is based on antisuppression training.

  8. Long-term tinnitus suppression with linear octave frequency transposition hearing AIDS.

    Directory of Open Access Journals (Sweden)

    Elisabeth Peltier

    Full Text Available Over the last three years of hearing aid dispensing, it was observed that among 74 subjects fitted with a linear octave frequency transposition (LOFT hearing aid, 60 reported partial or complete tinnitus suppression during day and night, an effect still lasting after several months or years of daily use. We report in more details on 38 subjects from whom we obtained quantified measures of tinnitus suppression through visual analog scaling and several additional psychoacoustic and audiometric measures. The long-term suppression seems independent of subject age, and of duration and subjective localization of tinnitus. A small but significant correlation was found with audiogram losses but not with high frequency loss slope. Long-term tinnitus suppression was observed for different etiologies, but with a low success rate for sudden deafness. It should be noted that a majority of subjects (23 had a history of noise exposure. Tinnitus suppression started after a few days of LOFT hearing aid use and reached a maximum after a few weeks of daily use. For nine subjects different amounts of frequency shifting were tried and found more or less successful for long-term tinnitus suppression, no correlation was found with tinnitus pitch. When the use of the LOFT hearing aid was stopped tinnitus reappeared within a day, and after re-using the LOFT aid it disappeared again within a day. For about one third of the 38 subjects a classical amplification or a non linear frequency compression aid was also tried, and no such tinnitus suppression was observed. Besides improvements in audiometric sensitivity to high frequencies and in speech discrimination scores, LOFT can be considered as a remarkable opportunity to suppress tinnitus over a long time scale. From a pathophysiological viewpoint these observations seem to fit with a possible re-attribution of activity to previously deprived cerebral areas corresponding to high frequency coding.

  9. Quantum Locality?

    Science.gov (United States)

    Stapp, Henry P.

    2012-05-01

    , in response to Griffiths' challenge, why a putative proof of locality that he has described is flawed.

  10. CONDITIONS FOR CSR MICROBUNCHING GAIN SUPPRESSION

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Cheng Ying [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Douglas, David R. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Li, Rui [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Tennant, Christopher D. [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); di Mitri, Simone [Elettra–Sincrotrone Trieste, 34149 Basovizza, Trieste, Italy

    2016-05-01

    The coherent synchrotron radiation (CSR) of a high brightness electron beam traversing a series of dipoles, such as transport arcs, may result in phase space degradation. On one hand, the CSR can perturb electron transverse motion in dispersive regions along the beamline, causing emittance growth. On the other hand, the CSR effect on the longitudinal beam dynamics could result in microbunching gain enhancement. For transport arcs, several schemes have been proposed* to suppress the CSR-induced emittance growth. Similarly, several scenarios have been introduced** to suppress CSR-induced microbunching gain, which however mostly aim for linac-based machines. In this paper we try to provide sufficient conditions for suppression of CSR-induced microbunching gain along a transport arc, analogous to*. Several example lattices are presented, with the relevant microbunching analyses carried out by our semi-analytical Vlasov solver***. The simulation results show that lattices satisfying the proposed conditions indeed have microbunching gain suppressed. We expect this analysis can shed light on lattice design approach that could suppress the CSR-induced microbunching gain.

  11. Interocular suppression in children with deprivation amblyopia.

    Science.gov (United States)

    Hamm, Lisa; Chen, Zidong; Li, Jinrong; Black, Joanna; Dai, Shuan; Yuan, Junpeng; Yu, Minbin; Thompson, Benjamin

    2017-04-01

    In patients with anisometropic or strabismic amblyopia, interocular suppression can be minimized by presenting high contrast stimulus elements to the amblyopic eye and lower contrast elements to the fellow eye. This suggests a structurally intact binocular visual system that is functionally suppressed. We investigated whether suppression can also be overcome by contrast balancing in children with deprivation amblyopia due to childhood cataracts. To quantify interocular contrast balance, contrast interference thresholds were measured using an established dichoptic global motion technique for 21 children with deprivation amblyopia, 14 with anisometropic or mixed strabismic/anisometropic amblyopia and 10 visually normal children (mean age mean=9.9years, range 5-16years). We found that interocular suppression could be overcome by contrast balancing in most children with deprivation amblyopia, at least intermittently, and all children with anisometropic or mixed anisometropic/strabismic amblyopia. However, children with deprivation amblyopia due to early unilateral or bilateral cataracts could tolerate only very low contrast levels to the stronger eye indicating strong suppression. Our results suggest that treatment options reliant on contrast balanced dichoptic presentation could be attempted in a subset of children with deprivation amblyopia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Local Foods, Local Places Summary Reports

    Science.gov (United States)

    These reports summarize community projects done with Local Foods, Local Places assistance, including farmers markets, cooperatives, community gardens, and other food-related enterprises that can boost local economies and drive revitalization.

  13. Quantum Locality?

    Energy Technology Data Exchange (ETDEWEB)

    Stapp, Henry

    2011-11-10

    vagaries that he cites do not upset the proof in question. It is show here in detail why the precise statement of this theorem justifies the specified application of CQT. It is also shown, in response to his challenge, why a putative proof of locality that he has proposed is not valid.

  14. Effects of thought suppression on episodic memory.

    Science.gov (United States)

    Rassin, E; Merckelbach, H; Muris, P

    1997-11-01

    Subjects were shown a short film fragment. Following this, one group of subjects (n = 26) was instructed to suppress their thoughts about the film, while the other group (n = 24) received no instructions. After 5 hrs subjects returned to the laboratory and completed a questionnaire testing their memory about the film. Results showed that suppression subjects reported a higher frequency of thoughts about the film than control subjects. No evidence was obtained for Wegner, Quillian, and Houston's (1996; Journal of Personality and Social Psychology, 71, 680-691) claim that suppression has an undermining effect on memory for chronology. Possible causes for the differences between the results as obtained by Wegner et al., and those found in the present study are discussed. These causes may pertain to the experimental design, but also to differences in emotional impact of the stimulus material that was used in both studies.

  15. Wing rock suppression using forebody vortex control

    Science.gov (United States)

    Ng, T. T.; Ong, L. Y.; Suarez, C. J.; Malcolm, G. N.

    1991-01-01

    Static and free-to-roll tests were conducted in a water tunnel with a configuration that consisted of a highly-slender forebody and 78-deg sweep delta wings. Flow visualization was performed and the roll angle histories were obtained. The fluid mechanisms governing the wing rock of this configuration were identified. Different means of suppressing wing rock by controlling the forebody vortices using small blowing jets were also explored. Steady blowing was found to be capable of suppressing wing rock, but significant vortex asymmetries had to be induced at the same time. On the other hand, alternating pulsed blowing on the left and right sides of the forebody was demonstrated to be potentially an effective means of suppressing wing rock and eliminating large asymmetric moments at high angles of attack.

  16. Quantum-mechanical suppression of bremsstrahlung

    Energy Technology Data Exchange (ETDEWEB)

    Becker-Szendy, R.; Keller, L.; Niemi, G.; Perl, M.; Rochester, L. [Stanford Univ., CA (United States); Anthony, P. [Stanford Univ., CA (United States)]|[Lawrence Livermore National Lab., CA (United States); Bosted, P. [American Univ., Washington, DC (United States); Cavalli-Sforza, M.; Kelley, L.; Klein, S. [Univ. of California, Santa Cruz, CA (United States)] [and others

    1994-12-01

    The authors have studied quantum-mechanical suppression of bremsstrahlung of low-energy 1-500 MeV photons from high-energy 25 GeV electrons. They have measured the LPM effect, where multiple scattering of the radiating electron destroys coherence required for the emission of low-energy photons, and the dielectric effect, where the emitted photon traveling in the radiator medium interferes with itself. For the experiment, the collaboration developed a novel method of extracting a parasitic low-intensity high-energy electron beam into the fixed target area during normal SLC operation of the accelerator. The results agree quantitatively with Migdal`s calculation of the LPM effect. Surface effects, for which there is no satisfactory theoretical prediction, are visible at low photon energies. For very thin targets, the suppression disappears, as expected. Preliminary results on dielectric suppression of bremsstrahlung are in qualitative agreement with the expectation.

  17. Suppression of charmonium production in hadron gas

    International Nuclear Information System (INIS)

    Faustov, R.N.; Vasilevskaya, I.G.

    1991-01-01

    The problem of J/ψ charmonium production suppression under heavy ion collisions is investigated. The processes of charmonium disintegration in hadron gas are considered: π+J/ψ → π+c+c-bar and ρ+J/ψ → D+D. Based on the results obtained one can assume that charmonium disintegration contribution to J/ψ production suppression under collisions with gas hadrons and the contribution conditioned by the production of quark-gluon plasma, appear to be the effects of similar order of magnitude

  18. Jet suppression measurement with the ATLAS detector

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00443411; The ATLAS collaboration

    2016-01-01

    A hot medium with a high density of unscreened color charges is produced in relativistic heavy ion collisions. Jets are produced at the early stages of this collision and are known to become attenuated as they propagate through the hot matter. One manifestation of this energy loss is a lower yield of jets emerging from the medium than expected in the absence of medium effects. Another manifestation of the energy loss is the modification of the dijet balance and the modification of fragmentation functions. In these proceedings, the latest ATLAS results on single jet suppression, dijet suppression, and modification of the jet internal structure in \\PbPb~collisions are presented.

  19. Star formation suppression in compact group galaxies

    DEFF Research Database (Denmark)

    Alatalo, K.; Appleton, P. N.; Lisenfeld, U.

    2015-01-01

    , bars, rings, tidal tails, and possibly nuclear outflows, though the molecular gas morphologies are more consistent with spirals and earlytype galaxies than mergers and interacting systems. Our CO-imaged HCG galaxies, when plotted on the Kennicutt-Schmidt relation, shows star formation (SF) suppression...... color space. This supports the idea that at least some galaxies in HCGs are transitioning objects, where a disruption of the existing molecular gas in the system suppresses SF by inhibiting the molecular gas from collapsing and forming stars efficiently. These observations, combined with recent work...

  20. Orientation-specific surround suppression in the primary visual cortex varies as a function of autistic tendency

    Directory of Open Access Journals (Sweden)

    Anastasia V Flevaris

    2015-01-01

    Full Text Available Individuals with autism spectrum disorder (ASD exhibit superior performance on tasks that rely on local details in an image, and they exhibit deficits in tasks that require integration of local elements into a unified whole. These perceptual abnormalities have been proposed to underlie many of the characteristic features of ASD, but the underlying neural mechanisms are poorly understood. Here, we investigated the degree to which orientation-specific surround suppression, a well-known form of contextual modulation in visual cortex, is associated with autistic tendency in neurotypical individuals. Surround suppression refers to the phenomenon that the response to a stimulus in the receptive field of a neuron is suppressed when it is surrounded by stimuli just outside the receptive field. The suppression is greatest when the center and surrounding stimuli share perceptual features such as orientation. Surround suppression underlies a number of fundamental perceptual processes that are known to be atypical in individuals with ASD, including perceptual grouping and perceptual pop-out. However, whether surround suppression in the primary visual cortex (V1 is related to autistic traits has not been directly tested before. We used fMRI to measure the neural response to a center Gabor when it was surrounded by Gabors having the same or orthogonal orientation, and calculated a suppression index (SI for each participant that denoted the magnitude of suppression in the same versus orthogonal conditions. SI was positively correlated with degree of autistic tendency in each individual, as measured by the Autism Quotient (AQ scale, a questionnaire designed to assess autistic traits in the general population. Age also correlated with SI and with autistic tendency in our sample, but did not account for the correlation between SI and autistic tendency. These results suggest a reduction in orientation-specific surround suppression in V1 with increasing autistic

  1. Change in ocean subsurface environment to suppress tropical cyclone intensification under global warming

    Science.gov (United States)

    Huang, Ping; Lin, I. -I; Chou, Chia; Huang, Rong-Hui

    2015-01-01

    Tropical cyclones (TCs) are hazardous natural disasters. Because TC intensification is significantly controlled by atmosphere and ocean environments, changes in these environments may cause changes in TC intensity. Changes in surface and subsurface ocean conditions can both influence a TC's intensification. Regarding global warming, minimal exploration of the subsurface ocean has been undertaken. Here we investigate future subsurface ocean environment changes projected by 22 state-of-the-art climate models and suggest a suppressive effect of subsurface oceans on the intensification of future TCs. Under global warming, the subsurface vertical temperature profile can be sharpened in important TC regions, which may contribute to a stronger ocean coupling (cooling) effect during the intensification of future TCs. Regarding a TC, future subsurface ocean environments may be more suppressive than the existing subsurface ocean environments. This suppressive effect is not spatially uniform and may be weak in certain local areas. PMID:25982028

  2. Experimental Results of Network-Assisted Interference Suppression Scheme Using Adaptive Beam-Tilt Switching

    Directory of Open Access Journals (Sweden)

    Tomoki Murakami

    2017-01-01

    Full Text Available This paper introduces a network-assisted interference suppression scheme using beam-tilt switching per frame for wireless local area network systems and its effectiveness in an actual indoor environment. In the proposed scheme, two access points simultaneously transmit to their own desired station by adjusting angle of beam-tilt including transmit power assisted from network server for the improvement of system throughput. In the conventional researches, it is widely known that beam-tilt is effective for ICI suppression in the outdoor scenario. However, the indoor effectiveness of beam-tilt for ICI suppression has not yet been indicated from the experimental evaluation. Thus, this paper indicates the effectiveness of the proposed scheme by analyzing multiple-input multiple-output channel matrices from experimental measurements in an office environment. The experimental results clearly show that the proposed scheme offers higher system throughput than the conventional scheme using just transmit power control.

  3. J/Ψ suppression as a signal for the quark-gluon plasma

    International Nuclear Information System (INIS)

    Wong, C.Y.

    1997-01-01

    The authors review the search for the quark-gluon plasma using the signal of the suppression of J/ψ production in high-energy heavy-ion collisions. Recent anomalous J/ψ suppression in high-energy Pb-Pb collisions observed by the NA50 Collaboration are examined and compared with earlier results from pA and nucleus-nucleus collisions with heavy ions of smaller mass numbers. The anomalous suppression of J/ψ production in Pb-Pb collisions can be explained as due to the occurrence of a new phase of strong J/ψ absorption, which sets in when the number of nucleon-nucleon collisions at a spatial point exceeds about 4 and corresponds to a local energy density of about 3.4 GeV/fm 3

  4. Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract.

    Science.gov (United States)

    Sun, Yun-Yan; Peng, Shiwen; Han, Liping; Qiu, Jin; Song, Liwen; Tsai, Yachea; Yang, Benjamin; Roden, Richard B S; Trimble, Cornelia L; Hung, Chien-Fu; Wu, T-C

    2016-02-01

    Two viral oncoproteins, E6 and E7, are expressed in all human papillomavirus (HPV)-infected cells, from initial infection in the genital tract to metastatic cervical cancer. Intramuscular vaccination of women with high-grade cervical intraepithelial neoplasia (CIN2/3) twice with a naked DNA vaccine, pNGVL4a-sig/E7(detox)/HSP70, and a single boost with HPVE6/E7 recombinant vaccinia vaccine (TA-HPV) elicited systemic HPV-specific CD8 T-cell responses that could traffic to the lesion and was associated with regression in some patients (NCT00788164). Here, we examine whether alteration of this vaccination regimen by administration of TA-HPV vaccination in the cervicovaginal tract, rather than intramuscular (IM) delivery, can more effectively recruit antigen-specific T cells in an orthotopic syngeneic mouse model of HPV16(+) cervical cancer (TC-1 luc). We found that pNGVL4a-sig/E7(detox)/HSP70 vaccination followed by cervicovaginal vaccination with TA-HPV increased accumulation of total and E7-specific CD8(+) T cells in the cervicovaginal tract and better controlled E7-expressing cervicovaginal TC-1 luc tumor than IM administration of TA-HPV. Furthermore, the E7-specific CD8(+) T cells in the cervicovaginal tract generated through the cervicovaginal route of vaccination expressed the α4β7 integrin and CCR9, which are necessary for the homing of the E7-specific CD8(+) T cells to the cervicovaginal tract. Finally, we show that cervicovaginal vaccination with TA-HPV can induce potent local HPV-16 E7 antigen-specific CD8(+) T-cell immune responses regardless of whether an HPV DNA vaccine priming vaccination was administered IM or within the cervicovaginal tract. Our results support future clinical translation using cervicovaginal TA-HPV vaccination. ©2015 American Association for Cancer Research.

  5. Antigen-Specific IP-10 Release Is a Sensitive Biomarker of Mycobacterium bovis Infection in Cattle.

    Directory of Open Access Journals (Sweden)

    Sven D C Parsons

    Full Text Available The most widely used ante-mortem diagnostic tests for tuberculosis in cattle are the tuberculin skin test and the interferon-gamma (IFN-γ release assay, both of which measure cell-mediated immune responses to Mycobacterium bovis infection. However, limitations in the performance of these tests results in a failure to identify all infected animals. In attempting to increase the range of diagnostic tests for tuberculosis, measurement of the cytokine IP-10 in antigen-stimulated blood has previously been shown to improve the detection of M. tuberculosis and M. bovis infection, in humans and African buffaloes (Syncerus caffer, respectively. In the present study, 60 cattle were identified by the single intradermal comparative tuberculin test as tuberculosis reactors (n = 24 or non-reactors (n = 36 and the release of IFN-γ and IP-10 in antigen-stimulated whole blood from these animals was measured using bovine specific ELISAs. There was a strong correlation between IP-10 and IFN-γ production in these samples. Moreover, measurement of the differential release of IP-10 in response to stimulation with M. bovis purified protein derivative (PPD and M. avium PPD distinguished between reactor and non-reactor cattle with a sensitivity of 100% (95% CI, 86%-100% and a specificity of 97% (95% CI, 85%-100%. These results suggest that IP-10 might prove valuable as a diagnostic biomarker of M. bovis infection in cattle.

  6. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Tramontano, Anna

    2011-01-01

    of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface

  7. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna

    2011-06-28

    The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen.

  8. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  9. Antigen Specificity of Type I NKT Cells Is Governed by TCR β-Chain Diversity.

    Science.gov (United States)

    Cameron, Garth; Pellicci, Daniel G; Uldrich, Adam P; Besra, Gurdyal S; Illarionov, Petr; Williams, Spencer J; La Gruta, Nicole L; Rossjohn, Jamie; Godfrey, Dale I

    2015-11-15

    NKT cells recognize lipid-based Ags presented by CD1d. Type I NKT cells are often referred to as invariant owing to their mostly invariant TCR α-chain usage (Vα14-Jα18 in mice, Vα24-Jα18 in humans). However, these cells have diverse TCR β-chains, including Vβ8, Vβ7, and Vβ2 in mice and Vβ11 in humans, joined to a range of TCR Dβ and Jβ genes. In this study, we demonstrate that TCR β-chain composition can dramatically influence lipid Ag recognition in an Ag-dependent manner. Namely, the glycolipids α-glucosylceramide and isoglobotrihexosylceramide were preferentially recognized by Vβ7(+) NKT cells from mice, whereas the α-galactosylceramide analog OCH, with a truncated sphingosine chain, was preferentially recognized by Vβ8(+) NKT cells from mice. We show that the influence of the TCR β-chain is due to a combination of Vβ-, Jβ-, and CDR3β-encoded residues and that these TCRs can recapitulate the selective Ag reactivity in TCR-transduced cell lines. Similar observations were made with human NKT cells where different CDR3β-encoded residues determined Ag preference. These findings indicate that NKT TCR β-chain diversity results in differential and nonhierarchical Ag recognition by these cells, which implies that some Ags can preferentially activate type I NKT cell subsets. Copyright © 2015 by The American Association of Immunologists, Inc.

  10. THE ANTIGEN-SPECIFIC CELL IN VITRO TESTS FOR POST-VACCINATION ANTIPLAGUE IMMUNITY FORMATION

    Directory of Open Access Journals (Sweden)

    A. N. Kulichenko

    2017-01-01

    Full Text Available The possibility of post-vaccination anti-plague immunity evaluation was researched using antigen-stimulated cells tests in vitro and cytometry analysis. The object of study — the blood samples of 17 people immunised by the live plague vaccine (Yersinia pestis EV epicutaneously. Blood taking was carried out before vaccination and after immunisation on 7 and on 21 days, in 3 and in 6 months. Intensity antigen reactivity of lymphocytes was detected by cell tests in vitro, analysing markers of early (CD45+CD3+CD25+ and late (CD45+CD3+HLA-DR+ lymphocyte activation using flow cytometry. The complex of water-soluble Y. pestis antigens and allergen — pestin PP was tested as antigen. The high stimulating potential was defined of the water-soluble antigens Y. pestis complex. It is shown that coefficient of stimulation of relative level T- lymphocytes which express receptors for IL-2 was positive for all observation times after immunisation. The coefficient of stimulation had maximum values at 21 days (56.37% and at 3 (47.41% months. In identifying HLADR-positive lymphocytes before vaccination, the negative coefficient of stimulation was indicated on 7 and 21 days and the positive coefficient of stimulation was indicated at 3 and at 6 months. Analysis of intensity expression of early and late lymphocyte activation markers dynamics showed the possibility and prospect of application of cellular in vitro tests for the laboratory evaluation of specific reactivity of cellular immunity in both the early (7 days and late (6 months periods after vaccination. The results can be the basis for developing a new algorithm for assessment of immunological effectiveness of vaccination people against plague. It is the algorithm based on the identification of lymphocyte activation markers by antigen stimulation in conditions in vitro.

  11. MHC-based detection of antigen-specific CD8(+) T cell responses

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker; Schumacher, Nana Maria Pii

    2010-01-01

    The hallmark of adaptive immunity is its ability to recognise a wide range of antigens and technologies that capture this diversity are therefore of substantial interest. New methods have recently been developed that allow the parallel analysis of T cell reactivity against vast numbers of different...

  12. Engineering antigen-specific T cells from genetically modified human hematopoietic stem cells in immunodeficient mice.

    Directory of Open Access Journals (Sweden)

    Scott G Kitchen

    Full Text Available There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR. Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.

  13. Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen

    NARCIS (Netherlands)

    Vermeij, Renee; Leffers, Ninke; Melief, Cornelis J.; Daemen, Toos; Nijman, Hans W.

    This review discusses the results of different immunization strategies, identifies possible drawbacks in study design and provides potential solutions for augmentation of clinical efficacy. A potential target for cancer immunotherapy is p53, as approximately 50% of ovarian cancer cells carry p53

  14. Induction and analysis of antigen-specific T cell responses in melanoma patients and animal models

    NARCIS (Netherlands)

    Bins, Adriaan Dirk

    2007-01-01

    This thesis introduces a novel T cell vaccination method that uses a tattoo machine to inject DNA in the skin of the vaccinee. In comparison to other experimental vaccination methods DNA tattooing is very strong: besides small laboratory animals also large animals mount strong T cell responses upon

  15. Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

    NARCIS (Netherlands)

    Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ceulemans, Ann; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc; Loembé, Marguerite Massinga; Mayanja, Harriet; Mascart, Francoise; van den Bergh, Rafael; Locht, Camille; Reiss, Peter; Cobelens, Frank; Ondoa, Pascale; Pakker, Nadine; Mugerwa, Roy

    2014-01-01

    Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of

  16. Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

    Science.gov (United States)

    Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ceulemans, Ann; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

    2014-01-01

    Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. Methods In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex. Results Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. Conclusion TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS. PMID:25415590

  17. Secondary immunization generates clonally related antigen-specific plasma cells and memory B cells.

    Science.gov (United States)

    Frölich, Daniela; Giesecke, Claudia; Mei, Henrik E; Reiter, Karin; Daridon, Capucine; Lipsky, Peter E; Dörner, Thomas

    2010-09-01

    Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their V(H) genes.

  18. Bordetella bronchiseptica antigen enhances the production of Mycoplasma hyopneumoniae antigen-specific immunoglobulin G in mice.

    Science.gov (United States)

    Yim, Seol-Hwa; Hahn, Tae-Wook; Joo, Hong-Gu

    2017-09-30

    We previously demonstrated that Bordetella ( B .) bronchiseptica antigen (Ag) showed high immunostimulatory effects on mouse bone marrow cells (BMs) while Mycoplasma ( M .) hyopneumoniae Ag showed low effects. The focus of this study was to determine if B. bronchiseptica Ag can enhance the M. hyopneumoniae Ag-specific immune response and whether the host's immune system can recognize both Ags. MTT assay results revealed that each or both Ags did not significantly change BM metabolic activity. Flow cytometry analysis using carboxyfluorescein succinimidyl ester showed that B. bronchiseptica Ag can promote the division of BMs. In cytokine and nitric oxide (NO) assays, B. bronchiseptica Ag boosted production of tumor necrosis factor-alpha in M. hyopneumoniae Ag-treated BMs, and combined treatment with both Ags elevated the level of NO in BMs compared to that from treatment of M. hyopneumoniae Ag alone. Immunoglobulin (Ig)G enzyme-linked immunosorbent assay using the sera of Ag-injected mice clearly indicated that B. bronchiseptica Ag can increase the production of M. hyopneumoniae Ag-specific IgG. This study provided information valuable in the development of M. hyopneumoniae vaccines and showed that B. bronchiseptica Ag can be used both as a vaccine adjuvant and as a vaccine Ag.

  19. Antigenic specificity of a monovalent versus polyvalent MOMP based Chlamydia pecorum vaccine in koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Kollipara, Avinash; Wan, Charles; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2013-02-06

    Chlamydia continues to be a major pathogen of koalas. The bacterium is associated with ocular, respiratory and urogenital tract infections and a vaccine is considered the best option to limit the decline of mainland koala populations. Over the last 20 years, efforts to develop a chlamydial vaccine in humans have focussed on the use of the chlamydial major outer membrane protein (MOMP). Potential problems with the use of MOMP-based vaccines relate to the wide range of genetic diversity in its four variable domains. In the present study, we evaluated the immune response of koalas vaccinated with a MOMP-based C. pecorum vaccine formulated with genetically and serologically diverse MOMPs. Animals immunised with individual MOMPs developed strong antibody and lymphocyte proliferation responses to both homologous as well as heterologous MOMP proteins. Importantly, we also showed that vaccine induced antibodies which effectively neutralised various heterologous strains of koala C. pecorum in an in vitro assay. Finally, we also demonstrated that the immune responses in monovalent as well as polyvalent MOMP vaccine groups were able to recognise whole chlamydial elementary bodies, illustrating the feasibility of developing an effective MOMP based C. pecorum vaccine that could protect against a range of strains. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  20. Antigenic specificity and morphologic characteristics of Chlamydia trachomatis, strain SFPD, isolated from hamsters with proliferative ileitis.

    Science.gov (United States)

    Fox, J G; Stills, H F; Paster, B J; Dewhirst, F E; Yan, L; Palley, L; Prostak, K

    1993-10-01

    Profound diarrhea associated with proliferating intestinal cells containing intraepithelial campylobacter-like organisms (ICLO) occurs in a variety of mammalian hosts, particularly swine and hamsters. Recently, intracellular bacteria were isolated from proliferative intestinal tissue of hamsters and propagated in intestine cell line 407. Oral inoculation of hamsters with cell culture lysates containing these organisms reproduced the disease in susceptible hamsters. In the present study, an intracellular bacterium from the INT 407 cell line was shown by a variety of techniques to be a member of the genus Chlamydia and has been designated Chlamydia sp. strain SFPD. McCoy cells infected with Chlamydia sp. strain SFPD demonstrated bright fluorescent-stained intracytoplasmic inclusions when examined with fluorescein-labeled species-specific C. trachomatis monoclonal antibodies. The organism also reacted to fluorescein-labeled polyclonal but not monoclonal ICLO "omega" antisera. Ultrastructural examination of the Chlamydia sp. strain SFPD from McCoy cells revealed electrondense elementary bodies and a less electron-dense reticulate-like body that was circular; both features are consistent in morphology to developmental forms of Chlamydia and do not conform to ICLO morphology. Molecular studies, 16S ribosomal sequence analysis, and sequencing of the outer membrane protein confirmed that the isolate is a C. trachomatis closely related to the mouse pneumonitis strain of C. trachomatis.

  1. Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.

    Science.gov (United States)

    Malter, M P; Frisch, C; Schoene-Bake, J C; Helmstaedter, C; Wandinger, K P; Stoecker, W; Urbach, H; Surges, R; Elger, C E; Vincent, A V; Bien, C G

    2014-09-01

    In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab(+)-LE.

  2. Shaped input distributions for structural damage localization

    DEFF Research Database (Denmark)

    Ulriksen, Martin Dalgaard; Bernal, Dionisio; Damkilde, Lars

    2018-01-01

    localization method is cast that operates on the premise of shaping inputs—whose spatial distribution is fixed—by use of a model, such that these inputs, in one structural subdomain at a time, suppress certain steady-state vibration quantities (depending on the type of damage one seeks to interrogate for......). Accordingly, damage is localized when the vibration signature induced by the shaped inputs in the damaged state corresponds to that in the reference state, hereby implying that the approach does not point directly to damage. Instead, it operates with interrogation based on postulated damage patterns...

  3. Suppression Situations in Multiple Linear Regression

    Science.gov (United States)

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  4. Cortisol suppresses radiation transformation in vitro

    International Nuclear Information System (INIS)

    Kennedy, A.R.

    1985-01-01

    It is reported that 10 -7 M cortisol has a significant suppressive effect on radiation-induced transformation in vitro in C3H10T 1/2 cells. Previously reported data showed a significant enhancing effect for similar experiments performed with cortisone. Thus, these two structurally similar glucocorticoid hormones have opposite effects on transformation induced by ionizing radiation. (author)

  5. Cooling device for reactor suppression pool

    International Nuclear Information System (INIS)

    Togasaki, Susumu; Kato, Kiyoshi.

    1994-01-01

    In a cooling device of a reactor suppression pool, when a temperature of pool water is abnormally increased and a heat absorbing portion is heated by, for example, occurrence of an accident, coolants are sent to the outside of the reactor container to actuates a thermally operating portion by the heat energy of coolants and drive heat exchanging fluids of a secondary cooling system. If the heat exchanging fluids are sent to a cooling portion, the coolants are cooled and returned to the heat absorbing portion of the suppression pool water. If the heat absorbing portion is heat pipes, the coolants are evaporated by heat absorbed from the suppression pool water, steams are sent to the thermally operating portion, then coolants are liquefied and caused to return to the heat absorbing portion. If the thermal operation portion is a gas turbine, the gas turbine is operated by the coolants, and it is converted to a rotational force to drive heat exchanging fluids by pumps. By constituting the cooling portion with a condensator, the coolants are condensed and liquefied and returned to the heat absorbing portion of the suppression pool water. (N.H.)

  6. Efflux inhibitor suppresses Streptococcus mutans virulence properties.

    Science.gov (United States)

    Zeng, Huihui; Liu, Jia; Ling, Junqi

    2017-04-01

    It is well established that efflux pumps play important roles in bacterial pathogenicity and efflux inhibitors (EIs) have been proved to be effective in suppressing bacterial virulence properties. However, little is known regarding the EI of Streptococcus mutans, a well-known caries-inducing bacterium. In this study, we identified the EI of S. mutans through ethidium bromide efflux assay and investigated how EI affected S. mutans virulence regarding the cariogenicity and stress response. Results indicated that reserpine, the identified EI, suppressed acid tolerance, mutacin production and transformation efficiency of S. mutans, and modified biofilm architecture and extracellular polysaccharide distribution. Suppressed glycosyltransferase activity was also noted after reserpine exposure. The data from quantitative real-time-PCR demonstrated that reserpine significantly altered the expression profile of quorum-sensing and virulence-associated genes. These findings suggest that reserpine represents a promising adjunct anticariogenic agent in that it suppresses virulence properties of S. mutans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Measuring colour rivalry suppression in amblyopia.

    Science.gov (United States)

    Hofeldt, T S; Hofeldt, A J

    1999-11-01

    To determine if the colour rivalry suppression is an index of the visual impairment in amblyopia and if the stereopsis and fusion evaluator (SAFE) instrument is a reliable indicator of the difference in visual input from the two eyes. To test the accuracy of the SAFE instrument for measuring the visual input from the two eyes, colour rivalry suppression was measured in six normal subjects. A test neutral density filter (NDF) was placed before one eye to induce a temporary relative afferent defect and the subject selected the NDF before the fellow eye to neutralise the test NDF. In a non-paediatric private practice, 24 consecutive patients diagnosed with unilateral amblyopia were tested with the SAFE. Of the 24 amblyopes, 14 qualified for the study because they were able to fuse images and had no comorbid disease. The relation between depth of colour rivalry suppression, stereoacuity, and interocular difference in logMAR acuity was analysed. In normal subjects, the SAFE instrument reversed temporary defects of 0.3 to 1. 8 log units to within 0.6 log units. In amblyopes, the NDF to reverse colour rivalry suppression was positively related to interocular difference in logMAR acuity (beta=1.21, psuppression as measured with the SAFE was found to agree closely with the degree of visual acuity impairment in non-paediatric patients with amblyopia.

  8. Pressure suppression facility for reactor container

    International Nuclear Information System (INIS)

    Fujii, Tadashi; Fukui, Toru; Kataoka, Yoshiyuki; Tominaga, Kenji.

    1993-01-01

    In a nuclear reactor comprising heat transfer surfaces from a pressure suppression pool at the inside to the outer circumferential pool at the outside, a means for supplying water from a water supply source at the outside of the container to the pools is disposed. Then, a heat transfer means is disposed between the pressure suppression chamber and the water cooling pool. The water supply means comprises a pressurization means for applying pressure to water of the water supply source and a water supply channel. Water is supplied into the pressure suppression pool and the outer circumferential pool to elevate the water level and extend the region of heat contact with the water cooling heat transfer means. In addition, since dynamic pressure is applied to the feedwater, for example, by pressurizing the water surface of the water supply source, water can be supplied without using dynamic equipments such as pumps. Then, since water-cooling heat transfer surface can be extended after occurrence of accident, enlargement of a reactor container and worsening of earthquake proofness can be avoided as much as possible, to improve function for suppressing the pressure in the container. Further, since water-cooling heat transfer region can be extended, the arrangement of the water source and the place to which water is supplied is made optional without considering the relative height therebetween, to improve earthquake proofness. (N.H.)

  9. Quarkonium suppression: Gluonic dissociation vs. colour screening

    Indian Academy of Sciences (India)

    mechanism comes into play for the initial conditions taken from the self screened parton cascade model in these studies. Keywords. Quark gluon plasma; J ψ; suppression; dissociation; colour screening. PACS No. 12.38.M. 1. Introduction. The last two decades have seen hectic activity towards identifying unique signatures ...

  10. Aralia elata (Miquel) Seemann Suppresses Inflammatory ...

    African Journals Online (AJOL)

    ISSN: 1596-5996 (print); 1596-9827 (electronic) ... The LPS-induced increase in the production of nitric oxide was concentration- dependently suppressed ... Aralia elata ethanol extract (AEE) exhibits protective ... temperature for 72 h and filtered. The filtered .... scavenging activity in a dose-dependent manner showing a ...

  11. Theoretical status of J/ψ suppression

    International Nuclear Information System (INIS)

    Gavin, S.

    1993-03-01

    High energy heavy ion collisions are expected to produce hadron densities far beyond the density in nuclei, ρ 0 = 0.16 fm -3 . Remarkably, no single measurement from the AGS and SPS light ion programs with projectiles A ≤ 32 stands out as unambiguous evidence of these extreme densities. To separate the high density signals from the background effects that result, e.g. from scattering with primary nucleons, careful systematic studies of hadron-nucleus, hA, and nucleus-nucleus, AB, data are needed. In this talk the author surveys the ongoing systematic study of the most notorious case in point -- J/ψ suppression. In principle, measurements of J/ψ suppression provide a probe of the densities obtained in AB collisions that is also sensitive to quark gluon plasma production. The latest results from SPS experiment NA38 reported by A. Romana in these proceedings show that the ratio of cross sections in the dimuon channel B μμ σ ψ /σ cont is reduced by a factor 0.50 ± 0.05 in central S+U compared to minimum bias pU collisions at 200 AGeV. This is precisely the sort of suppression that one expects if high densities are obtained. On the other hand, a target-mass dependence suggestive of this suppression is found in hA collisions where high densities are not expected. At 200 GeV, NA38 finds that B μμ σ ψ /σ cont falls to 0.84 ± 0.08 in pU compared to pCu. The hA suppression in this kinematic regime is likely due to a combination of nuclear effects: nucleon absorption and shadowing

  12. Error suppression and error correction in adiabatic quantum computation: non-equilibrium dynamics

    International Nuclear Information System (INIS)

    Sarovar, Mohan; Young, Kevin C

    2013-01-01

    While adiabatic quantum computing (AQC) has some robustness to noise and decoherence, it is widely believed that encoding, error suppression and error correction will be required to scale AQC to large problem sizes. Previous works have established at least two different techniques for error suppression in AQC. In this paper we derive a model for describing the dynamics of encoded AQC and show that previous constructions for error suppression can be unified with this dynamical model. In addition, the model clarifies the mechanisms of error suppression and allows the identification of its weaknesses. In the second half of the paper, we utilize our description of non-equilibrium dynamics in encoded AQC to construct methods for error correction in AQC by cooling local degrees of freedom (qubits). While this is shown to be possible in principle, we also identify the key challenge to this approach: the requirement of high-weight Hamiltonians. Finally, we use our dynamical model to perform a simplified thermal stability analysis of concatenated-stabilizer-code encoded many-body systems for AQC or quantum memories. This work is a companion paper to ‘Error suppression and error correction in adiabatic quantum computation: techniques and challenges (2013 Phys. Rev. X 3 041013)’, which provides a quantum information perspective on the techniques and limitations of error suppression and correction in AQC. In this paper we couch the same results within a dynamical framework, which allows for a detailed analysis of the non-equilibrium dynamics of error suppression and correction in encoded AQC. (paper)

  13. Suppression of plasma turbulence during optimised shear configurations in JET

    International Nuclear Information System (INIS)

    Conway, G.D.; Borba, D.N.; Alper, B.

    1999-08-01

    Density turbulence suppression is observed in the internal transport barrier (ITB) region of JET discharges with optimised magnetic shear. The suppression occurs in two stages. First, low frequency turbulence is reduced across the plasma core by a toroidal velocity shear generated by intense auxiliary heating. Then when the ITB forms, high frequency turbulence is reduced locally within the steep pressure gradient region of the ITB, consistent with the effects of enhanced E x B poloidal shear. The turbulence suppression is correlated with reduced plasma transport and improved fusion performance. Much effort has been spent in recent years in developing alternative scenarios for operating tokamak fusion reactors. One particular scenario involves reversing or reducing the central magnetic shear to form an internal transport barrier (ITB). The result is reduced plasma core energy transport and enhanced fusion performance. It is believed that ITBs may be formed through a combination of E x B velocity shear and magnetic shear stabilisation of plasma turbulence and instabilities. In this Letter we present results from JET optimised shear discharges showing that turbulence suppression during ITB formation occurs in two stages. First low frequency turbulence is reduced across the plasma core, coinciding with a region of strong toroidal velocity shear; then high frequency turbulence is locally suppressed around the ITB region, consistent with enhanced pressure gradient driven E x B poloidal shear. The measurements were made using a system of X-mode reflectometers consisting of two, dual-channel toroidal correlation reflectometers at 75 GHz (covering plasma outboard edge) and 105 GHz (core and inboard edge), and a 92-96 GHz swept frequency radial correlation reflectometer (plasma core). Reflectometry is a powerful tool for measuring density fluctuations. The highly localised reflection of the microwave beam gives excellent spatial localisation. Measurements can be made

  14. Value of fat suppression and dynamic contrast-enhanced MRI in the diagnosis of insulinoma

    International Nuclear Information System (INIS)

    Xu Zengbin; Ruan Lingxiang; Peng Zhiyi; Zhang Minming; Xu Shunliang; Zhang Xidao

    2003-01-01

    Objective: To evaluate the value of fat suppression and dynamic contrast-enhanced MRI in the preoperative localization of insulinoma. Methods: Twelve cases with pathologically proven insulinoma were evaluated with MRI. SE T 1 WI, FSE T 2 WI, T 1 WI and T 2 WI with fat suppression, dynamic contrast-enhanced FMPSPGR sequences were used in MR scanning. Results: On SE T 1 WI, the lesions displayed hypointense in 4, isointense in 8 cases. Lesions showed hyperintense in 4, isointense in 8 cases on FSE T 2 WI. In contrast, 7 cases appeared as hypointense on T 1 WI with fat suppression and 6 cases appeared as hyperintense on T 2 WI with fat suppression. With dynamic contrast-enhanced FMPSPGR sequence 11 of 12 insulinomas were detected. In the arterial phase, the lesions presented as hyperintense with different degrees in 11 cases and isointense in 1 case. 6 cases remained hyperintense and 6 cases were isointense in pancreatic parenchymal and portal phase. 4 lesions were identified only in dynamic enhancement images. The diagnostic accuracy of insulinoma by dynamic contrast-enhanced MRI was 91.7% (11/12) as compared with histological study. Conclusion: The results indicate that dynamic contrast-enhanced MRI is an sensitive and accurate method for the preoperative localization of insulinoma

  15. Suppressed visual looming stimuli are not integrated with auditory looming signals: Evidence from continuous flash suppression.

    Science.gov (United States)

    Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond

    2015-01-01

    Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.

  16. Benchmark enclosure fire suppression experiments - phase 1 test report.

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

    2007-06-01

    A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

  17. [The advances of suppression in research of amblyopia].

    Science.gov (United States)

    Liu, S; Liu, H

    2016-04-11

    Suppression that is the result of interocular competition is an important machanism of amblyopia. The imbalance of suppression may lead the consequence to amblyopia. In the early study, researchers had raised the theory of II. Quadratic Summation which had revealed the relationship of interocular interaction and suppression. In some basic researches, other studies had showed the most possible anatomic location of suppression. Recently, researchers found a new method to quantify the interocular suppression named the noise model. Further studies found a novel disinhibition therapy to treat amblyopia. We summarized the research advances in suppression and disinhibition treatment in amblyopia. (Chin J Ophthalmol, 2016, 52: 305-308).

  18. Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

    International Nuclear Information System (INIS)

    Lee, So-Yeon; Kim, Sun Ki; Jee, Won-Hee; Kim, Jung-Man

    2011-01-01

    To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using κ coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with (κ = 0.87) or without (κ = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

  19. Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Yeon; Kim, Sun Ki [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Jee, Won-Hee [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Catholic University of Korea, Diagnostic Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seoul (Korea, Republic of); Kim, Jung-Man [Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

    2011-02-15

    To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using {kappa} coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with ({kappa} = 0.87) or without ({kappa} = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

  20. Overcoming fixation with repeated memory suppression.

    Science.gov (United States)

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  1. Magnetic fusion development for global warming suppression

    International Nuclear Information System (INIS)

    Li Jiangang; Zhang Jie; Duan Xuru

    2010-01-01

    Energy shortage and environmental pollution are two critical issues for human beings in the 21st century. There is an urgent need for new sustainable energy to meet the fast growing demand for clean energy. Fusion is one of the few options which may be able to satisfy the requirement for large scale sustainable energy generation and global warming suppression and therefore must be developed as quickly as possible. Fusion research has been carried out for the past 50 years. It is too long to wait for another 50 years to generate electricity by fusion. A much more aggressive approach should be taken with international collaboration towards the early use of fusion energy to meet the urgent needs for energy and global warming suppression.

  2. Suppression of Rabi oscillations for moving atoms

    International Nuclear Information System (INIS)

    Navarro, B.; Egusquiza, I. L.; Muga, J. G.; Hegerfeldt, G. C.

    2003-01-01

    The well-known laser-induced Rabi oscillations of a two-level atom are shown to be suppressed under certain conditions when the atom is entering a laser-illuminated region. For temporal Rabi oscillations the effect has two regimes: a first classical-like one, taking place at intermediate atomic velocities, and a second purely quantum case at low velocities. The classical regime is associated with the formation of incoherent internal states of the atom in the laser region, whereas in the quantum, low velocity regime the laser projects the atom onto a pure internal state that can be controlled by detuning. Spatial Rabi oscillations are only suppressed in this low velocity, quantum regime

  3. Sleep deprivation suppresses aggression in Drosophila

    Science.gov (United States)

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  4. Suppression of Poxvirus Replication by Resveratrol.

    Science.gov (United States)

    Cao, Shuai; Realegeno, Susan; Pant, Anil; Satheshkumar, Panayampalli S; Yang, Zhilong

    2017-01-01

    Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV), the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

  5. Suppression of Poxvirus Replication by Resveratrol

    Directory of Open Access Journals (Sweden)

    Shuai Cao

    2017-11-01

    Full Text Available Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV, the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

  6. Managing for soil health can suppress pests

    Directory of Open Access Journals (Sweden)

    Amanda Hodson

    2016-08-01

    Full Text Available A “healthy” soil can be thought of as one that functions well, both agronomically and ecologically, and one in which soil biodiversity and crop management work in synergy to suppress pests and diseases. UC researchers have pioneered many ways of managing soil biology for pest management, including strategies such as soil solarization, steam treatment and anaerobic soil disinfestation, as well as improvements on traditional methods, such as reducing tillage, amending soil with organic materials, and cover cropping. As managing for soil health becomes more of an explicit focus due to restrictions on the use of soil fumigants, integrated soil health tests will be needed that are validated for use in California. Other research needs include breeding crops for disease resistance and pest suppressive microbial communities as well as knowledge of how beneficial organisms influence plant health.

  7. Prevention and suppression of metal packing fires.

    Science.gov (United States)

    Roberts, Mark; Rogers, William J; Sam Mannan, M; Ostrowski, Scott W

    2003-11-14

    Structured packing has been widely used because of large surface area that makes possible columns with high capacity and efficiency. The large surface area also contributes to fire hazards because of hydrocarbon deposits that can easily combust and promote combustion of the thin metal packing materials. Materials of high surface area that can fuel fires include reactive metals, such as titanium, and materials that are not considered combustible, such as stainless steel. Column design and material selection for packing construction is discussed together with employee training and practices for safe column maintenance and operations. Presented also are methods and agents for suppression of metal fires. Guidance for prevention and suppression of metal fires is related to incidents involving packing fires in columns.

  8. Compton suppression through rise-time analysis

    International Nuclear Information System (INIS)

    Selvi, S.; Celiktas, C.

    2007-01-01

    We studied Compton suppression for 60 Co and 137 Cs radioisotopes using a signal selection criterion based on contrasting the fall time of the signals composing the photo peak with those composing the Compton continuum. The fall time criterion is employed by using the pulse shape analysis observing the change in the fall times of the gamma-ray pulses. This change is determined by measuring the changes in the rise times related to the fall time of the scintillator and the timing signals related to the fall time of the input signals. We showed that Compton continuum suppression is achieved best via the precise timing adjustment of an analog rise-time analyzer connected to a NaI(Tl) scintillation spectrometer

  9. Abnormal Grain Growth Suppression in Aluminum Alloys

    Science.gov (United States)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  10. Pressure suppression device for a reactor container

    International Nuclear Information System (INIS)

    Shimizu, Toshiaki

    1982-01-01

    Purpose: To prevent damages in drain pipes or the likes upon the water level increase due to blowing of incompressible gases. Constitution: An exhaust pipe for guiding escaping steams is connected to a main steam releaf valve. The exhaust pipe is guided into pressure-suppression-chamber water through the inside of a dry-well and by way of a vent pipe, a vent header and a drain pipe or a downcomer. Since the exhaust pipe is not exposed to the water surface inside the pressure suppression chamber, even if steams blow out into the dry-well by the rapture of pipeways or the likes to rapidly increase the water level, the water surface does not hit on the exhaust pipe, whereby the damages for the exhaust pipe and support members can be prevented to improve the reliability. (Seki, T.)

  11. Background suppression of infrared small target image based on inter-frame registration

    Science.gov (United States)

    Ye, Xiubo; Xue, Bindang

    2018-04-01

    We propose a multi-frame background suppression method for remote infrared small target detection. Inter-frame information is necessary when the heavy background clutters make it difficult to distinguish real targets and false alarms. A registration procedure based on points matching in image patches is used to compensate the local deformation of background. Then the target can be separated by background subtraction. Experiments show our method serves as an effective preliminary of target detection.

  12. TU-CD-BRA-11: Application of Bone Suppression Technique to Inspiratory/expiratory Chest Radiography

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, R; Sanada, S [Kanazawa University, Kanazawa, Ishikawa (Japan); Sakuta, K; Kawashima, H [Kanazawa University Hospital, Kanazawa, Ishikawa (Japan); Kishitani, Y [TOYO Corporation, Chuoh-ku, Tokyo (Japan)

    2015-06-15

    Purpose: The bone suppression technique based on advanced image processing can suppress the conspicuity of bones on chest radiographs, creating soft tissue images normally obtained by the dual-energy subtraction technique. This study was performed to investigate the usefulness of bone suppression technique in quantitative analysis of pulmonary function in inspiratory/expiratory chest radiography. Methods: Commercial bone suppression image processing software (ClearRead; Riverain Technologies) was applied to paired inspiratory/expiratory chest radiographs of 107 patients (normal, 33; abnormal, 74) to create corresponding bone suppression images. The abnormal subjects had been diagnosed with pulmonary diseases, such as pneumothorax, pneumonia, emphysema, asthma, and lung cancer. After recognition of the lung area, the vectors of respiratory displacement were measured in all local lung areas using a cross-correlation technique. The measured displacement in each area was visualized as displacement color maps. The distribution pattern of respiratory displacement was assessed by comparison with the findings of lung scintigraphy. Results: Respiratory displacement of pulmonary markings (soft tissues) was able to be quantified separately from the rib movements on bone suppression images. The resulting displacement map showed a left-right symmetric distribution increasing from the lung apex to the bottom region of the lung in many cases. However, patients with ventilatory impairments showed a nonuniform distribution caused by decreased displacement of pulmonary markings, which were confirmed to correspond to area with ventilatory impairments found on the lung scintigrams. Conclusion: The bone suppression technique was useful for quantitative analysis of respiratory displacement of pulmonary markings without any interruption of the rib shadows. Abnormal areas could be detected as decreased displacement of pulmonary markings. Inspiratory/expiratory chest radiography combined

  13. Myc suppression of Nfkb2 accelerates lymphomagenesis

    International Nuclear Information System (INIS)

    Keller, Ulrich; Huber, Jürgen; Nilsson, Jonas A; Fallahi, Mohammad; Hall, Mark A; Peschel, Christian; Cleveland, John L

    2010-01-01

    Deregulated c-Myc expression is a hallmark of several human cancers where it promotes proliferation and an aggressive tumour phenotype. Myc overexpression is associated with reduced activity of Rel/NF-κB, transcription factors that control the immune response, cell survival, and transformation, and that are frequently altered in cancer. The Rel/NF-κB family member NFKB2 is altered by chromosomal translocations or deletions in lymphoid malignancies and deletion of the C-terminal ankyrin domain of NF-κB2 augments lymphocyte proliferation. Precancerous Eμ-Myc-transgenic B cells, Eμ-Myc lymphomas and human Burkitt lymphoma samples were assessed for Nfkb2 expression. The contribution of Nfkb2 to Myc-driven apoptosis, proliferation, and lymphomagenesis was tested genetically in vivo. Here we report that the Myc oncoprotein suppresses Nfkb2 expression in vitro in primary mouse fibroblasts and B cells, and in vivo in the Eμ-Myc transgenic mouse model of human Burkitt lymphoma (BL). NFKB2 suppression by Myc was also confirmed in primary human BL. Promoter-reporter assays indicate that Myc-mediated suppression of Nfkb2 occurs at the level of transcription. The contribution of Nfkb2 to Myc-driven lymphomagenesis was tested in vivo, where Nfkb2 loss was shown to accelerate lymphoma development in Eμ-Myc transgenic mice, by impairing Myc's apoptotic response. Nfkb2 is suppressed by c-Myc and harnesses Myc-driven lymphomagenesis. These data thus link Myc-driven lymphomagenesis to the non-canonical NF-κB pathway

  14. Hangar Fire Suppression Utilizing Novec 1230

    Science.gov (United States)

    2018-01-01

    fuel fires in aircraft hangars. A 30×30×8-ft concrete-and-steel test structure was constructed for this test series. Four discharge assemblies...that agent concentration in the test structure exceeded the required extinguishing concentration for at least 5 min after discharge. Two fire ...involved suppression of a 4.6-gal, approximately 5-ft diameter, Jet-A pool fire . Both fires were successfully extinguished by the Novec 1230 discharge

  15. Thought Suppression in Patients With Bipolar Disorder

    OpenAIRE

    Miklowitz, David J.; Alatiq, Yousra; Geddes, John R.; Goodwin, Guy M.; Williams, J. Mark G.

    2010-01-01

    Suppression of negative thoughts has been observed under experimental conditions among patients with major depressive disorder (MDD) but has never been examined among patients with bipolar disorder (BD). Patients with BD (n = 36), patients with MDD (n = 20), and healthy controls (n = 20) completed a task that required unscrambling 6-word strings into 5-word sentences, leaving out 1 word. The extra word allowed the sentences to be completed in a negative, neutral, or ?hyperpositive? (manic/goa...

  16. Mechanisms underlying UV-induced immune suppression

    International Nuclear Information System (INIS)

    Ullrich, Stephen E.

    2005-01-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression

  17. Suppression of radiation excitation in focusing environment

    International Nuclear Information System (INIS)

    Huang, Z.; Ruth, R.D.

    1996-12-01

    Radiation damping and quantum excitation in an electron damping ring and a straight focusing channel are reviewed. They are found to be the two limiting cases in the study of a general bending and focusing combined system. In the intermediate regime where the radiation formation length is comparable to the betatron wavelength, quantum excitation can be exponentially suppressed by focusing field. This new regime may have interesting applications in the generation of ultra-low emittance beams

  18. Local Stereo Matching Using Adaptive Local Segmentation

    NARCIS (Netherlands)

    Damjanovic, S.; van der Heijden, Ferdinand; Spreeuwers, Lieuwe Jan

    We propose a new dense local stereo matching framework for gray-level images based on an adaptive local segmentation using a dynamic threshold. We define a new validity domain of the fronto-parallel assumption based on the local intensity variations in the 4-neighborhood of the matching pixel. The

  19. Suppressing bullfrog larvae with carbon dioxide

    Science.gov (United States)

    Gross, Jackson A.; Ray, Andrew; Sepulveda, Adam J.; Watten, Barnaby J.; Densmore, Christine L.; Layhee, Megan J.; Mark Abbey-Lambert,; ,

    2014-01-01

    Current management strategies for the control and suppression of the American Bullfrog (Lithobates catesbeianus = Rana catesbeiana Shaw) and other invasive amphibians have had minimal effect on their abundance and distribution. This study evaluates the effects of carbon dioxide (CO2) on pre- and prometamorphic Bullfrog larvae. Bullfrogs are a model organism for evaluating potential suppression agents because they are a successful invader worldwide. From experimental trials we estimated that the 24-h 50% and 99% lethal concentration (LC50 and LC99) values for Bullfrog larvae were 371 and 549 mg CO2/L, respectively. Overall, larvae that succumbed to experimental conditions had a lower body condition index than those that survived. We also documented sublethal changes in blood chemistry during prolonged exposure to elevated CO2. Specifically, blood pH decreased by more than 0.5 pH units after 9 h of exposure and both blood partial pressure of CO2 (pCO2) and blood glucose increased. These findings suggest that CO2 treatments can be lethal to Bullfrog larvae under controlled laboratory conditions. We believe this work represents the necessary foundation for further consideration of CO2 as a potential suppression agent for one of the most harmful invaders to freshwater ecosystems.

  20. Subjective duration distortions mirror neural repetition suppression.

    Science.gov (United States)

    Pariyadath, Vani; Eagleman, David M

    2012-01-01

    Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression. Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli) followed by a line presented at a different orientation (oddball stimulus). We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials. Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

  1. Variation in plant defense suppresses herbivore performance

    Science.gov (United States)

    Pearse, Ian; Paul, Ryan; Ode, Paul J.

    2018-01-01

    Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.

  2. Abscopal suppression of bone marrow erythropoiesis

    International Nuclear Information System (INIS)

    Werts, E.D.; Johnson, M.J.; DeGowin, R.L.

    1978-01-01

    Abscopal responses of hemopoietic tissue, which we noted in preliminary studies of mice receiving partial-body irradiation, led us to clarify these effects. In studies reported here, one hind leg of CF-1 female mice received 1000, 5000, or 10,000 rad of x radiation. We found a persistent shift from medullary to splenic erythropoiesis preventing anemia in mice receiving 5000 or 10,000 rad. Splenectomy prior to 5000-rad irradiation resulted in anemia, which was not ameliorated by exposure to intermittent hypoxia. Despite evidence for increased levels of erythropoietin in the animals, namely, a reticulocytosis and increased erythrocyte radioiron incorporation, both 59 Fe uptake and erythroblast counts in shielded marrow remained below normal. We found 50 to 90% suppression of the growth of marrow stromal colonies (MSC) from bone marrow aspirates of the shielded and irradiated femoral marrow at 1 month and at least 20% depression of MSC at 1 year, with each dose. We conclude that: (i) high doses of x radiation to one leg of mice caused prolonged suppression of medullary erythropoiesis with splenic compensation to prevent anemia; (ii) splenectomy, anemia, and hypoxia prevented the severe abscopal depression of medullary erythropoiesis; and (iii) suppressed medullary erythropoiesis with decreased growth of MSC suggested a change in the hemopoietic microenvironment of the bone marrow

  3. Adaptive Filtering for Aeroservoelastic Response Suppression, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — CSA Engineering proposes the design of an adaptive aeroelastic mode suppression for advanced fly-by-wire aircraft, which will partition the modal suppression...

  4. Exploring Genetic Suppression Interactions on a Global Scale

    OpenAIRE

    van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C.; Yamaguchi, Takafumi N.; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire

    2016-01-01

    Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insig...

  5. Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

    Science.gov (United States)

    Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

    2005-03-01

    The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

  6. Compost made of organic wastes suppresses fusariosis

    Science.gov (United States)

    Kuryntseva, Polina; Galitskaya, Polina; Biktasheva, Liliya; Selivanovkaya, Svetlana

    2017-04-01

    Fungal plant diseases cause dramatic yield losses worldwide. Usually, pesticides are used for soil sanitation, and it results in practically pest-free soils, although pesticides cause a biological vacuum, which present many horticultural disadvantages. Suppressive composts, which possess both fertilizing properties for plants and inhibiting properties for plant pathogens, represent an effective and environmentally friendly alternative to conventional pesticides. In this study, composts obtained from agricultural organic wastes were applied to suppress Fusarium oxysporum of tomato plants in model experiments. Composts were made of mixtures of the widespread organic wastes sampled in Tatarstan (Russia): straw (SW), corn wastes (CW), chicken manure (ChM), cattle manure (CM) and swine manure (SM). 11 two- and three-component mixtures were prepared to obtain the optimal carbon-nitrogen, moisture and pH balances, and composted for 210 days. It was found that the thermophilic phase of composting in all the mixtures lasted from 2 to 35 days, and was characterized by significant fluctuations in temperature, i.e. from 27°C to 59°C. In the initial mixtures, the dissolved organic carbon (DOC) content was between 10 and 62 mg kg-1; it fell significantly on day 13, and then continuously decreased up to day 102, and subsequently remained low. For all the mixtures, maximal respiration activity was observed in the beginning of composting (231.9 mg CO2-C g-1 day-1). After 23 days, this parameter decreased significantly, and fluctuations subsided. The phytotoxicity of the initial compost mixtures varied from 18% (SW+SM) to 100% (CW+ChM+SM, CW+ChM); however, the trends in the dynamics were similar. After 120 days of composting, 5 of 11 samples were not phytotoxic. After 120 days of composting, each mixture was divided into two parts; one was inoculated with a biopreparation consisting of four microbial strains (Trichoderma asperellum, Pseudomonas putida, Pseudomonas fluorescens and

  7. One-tone suppression in the frog auditory nerve

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Jørgensen, M B

    1996-01-01

    Sixty-seven fibers of a sample of 401 in the auditory nerve of grassfrogs (Rana temporaria) showed one-tone suppression, i.e., their spontaneous activity was suppressed by tones. All fibers were afferents from the amphibian papilla with best frequencies between 100 and 400 Hz. Best suppression...

  8. Venture capital: States suffer as suppression expenses climb

    Science.gov (United States)

    Krista Gebert

    2008-01-01

    The high cost of suppressing wildfires is taking a toll on federal and state agencies alike. Large wildland fires are complex, costly events influenced by a vast array of physical, climatic, and social factors. During five of the last eight years, the Forest Services' wildfire suppression expenditures have topped $1 billion, and total federal wildland suppression...

  9. Microbial enrichment to enhance the disease suppressive activity of compost

    NARCIS (Netherlands)

    Postma, J.; Montenari, M.; Boogert, van den P.H.J.F.

    2003-01-01

    Compost amended soil has been found to be suppressive against plant diseases in various cropping systems. The level and reproducibility of disease suppressive properties of compost might be increased by the addition of antagonists. In the present study, the establishment and suppressive activity of

  10. Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

    Directory of Open Access Journals (Sweden)

    Szczygieł Dorota

    2015-09-01

    Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

  11. Locally Finite Root Supersystems

    OpenAIRE

    Yousofzadeh, Malihe

    2013-01-01

    We introduce the notion of locally finite root supersystems as a generalization of both locally finite root systems and generalized root systems. We classify irreducible locally finite root supersystems.

  12. Local stressors reduce coral resilience to bleaching.

    Science.gov (United States)

    Carilli, Jessica E; Norris, Richard D; Black, Bryan A; Walsh, Sheila M; McField, Melanie

    2009-07-22

    Coral bleaching, during which corals lose their symbiotic dinoflagellates, typically corresponds with periods of intense heat stress, and appears to be increasing in frequency and geographic extent as the climate warms. A fundamental question in coral reef ecology is whether chronic local stress reduces coral resistance and resilience from episodic stress such as bleaching, or alternatively promotes acclimatization, potentially increasing resistance and resilience. Here we show that following a major bleaching event, Montastraea faveolata coral growth rates at sites with higher local anthropogenic stressors remained suppressed for at least 8 years, while coral growth rates at sites with lower stress recovered in 2-3 years. Instead of promoting acclimatization, our data indicate that background stress reduces coral fitness and resilience to episodic events. We also suggest that reducing chronic stress through local coral reef management efforts may increase coral resilience to global climate change.

  13. Psychophysical research progress of interocular suppression in amblyopic visual system

    Directory of Open Access Journals (Sweden)

    Jing-Jing Li

    2016-03-01

    Full Text Available Some recent animal experiments and psychophysical studies indicate that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression, and interocular suppression is a key mechanism in visual deficits experienced by patients with amblyopia. The aim of this review is to provide an overview of recent psychophysical findings that have investigated the important role of interocular suppression in amblyopia, the measurement and modulation of suppression, and new dichoptic treatment intervention that directly target suppression.

  14. Tolerogenic dendritic cells pulsed with enterobacterial extract suppress development of colitis in the severe combined immunodeficiency transfer model

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Gad, M; Kristensen, N N

    2007-01-01

    Immunomodulatory dendritic cells (DCs) that induce antigen-specific T-cell tolerance upon in vivo adoptive transfer are promising candidates for immunotherapy of autoimmune diseases. The feasibility of such a strategy has recently proved its efficacy in animal models of allotransplantation and ex...

  15. Subjective duration distortions mirror neural repetition suppression.

    Directory of Open Access Journals (Sweden)

    Vani Pariyadath

    Full Text Available Subjective duration is strongly influenced by repetition and novelty, such that an oddball stimulus in a stream of repeated stimuli appears to last longer in duration in comparison. We hypothesize that this duration illusion, called the temporal oddball effect, is a result of the difference in expectation between the oddball and the repeated stimuli. Specifically, we conjecture that the repeated stimuli contract in duration as a result of increased predictability; these duration contractions, we suggest, result from decreased neural response amplitude with repetition, known as repetition suppression.Participants viewed trials consisting of lines presented at a particular orientation (standard stimuli followed by a line presented at a different orientation (oddball stimulus. We found that the size of the oddball effect correlates with the number of repetitions of the standard stimulus as well as the amount of deviance from the oddball stimulus; both of these results are consistent with a repetition suppression hypothesis. Further, we find that the temporal oddball effect is sensitive to experimental context--that is, the size of the oddball effect for a particular experimental trial is influenced by the range of duration distortions seen in preceding trials.Our data suggest that the repetition-related duration contractions causing the oddball effect are a result of neural repetition suppression. More generally, subjective duration may reflect the prediction error associated with a stimulus and, consequently, the efficiency of encoding that stimulus. Additionally, we emphasize that experimental context effects need to be taken into consideration when designing duration-related tasks.

  16. Bone-suppressed radiography using machine learning

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

  17. Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

    Science.gov (United States)

    Hwang, J K; Erkhembaatar, M; Gu, D R; Lee, S H; Lee, C H; Shin, D M; Lee, Y R; Kim, M S

    2014-07-01

    Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. © International & American Associations for Dental Research.

  18. Bone-suppressed radiography using machine learning

    International Nuclear Information System (INIS)

    Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung

    2016-01-01

    The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

  19. Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

    International Nuclear Information System (INIS)

    Ikuta, Togo; Kurosumi, Masafumi; Yatsuoka, Toshimasa; Nishimura, Yoji

    2016-01-01

    Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc"M"i"n"/"+mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

  20. Tissue distribution of aryl hydrocarbon receptor in the intestine: Implication of putative roles in tumor suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ikuta, Togo, E-mail: togo@cancer-c.pref.saitama.jp [Department of Cancer Prevention, Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Kurosumi, Masafumi, E-mail: mkurosumi@cancer-c.pref.saitama.jp [Division of Pathology, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Yatsuoka, Toshimasa, E-mail: yatsuoka-gi@umin.ac.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan); Nishimura, Yoji, E-mail: yojinish@cancr-c.pref.saitama.jp [Division of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806 (Japan)

    2016-05-01

    Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc{sup Min/+}mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression. - Highlights: • In the normal intestine, AhR was mainly localized in stroma containing immune cells. • In the tumor tissue, AhR expression was found in both stromal and tumor cells. • AhR knockdown promoted cell growth in colon cancer cell lines.

  1. Fire suppression as a thermal implosion

    Science.gov (United States)

    Novozhilov, Vasily

    2017-01-01

    The present paper discusses the possibility of the thermal implosion scenario. This process would be a reverse of the well known thermal explosion (autoignition) phenomenon. The mechanism for thermal implosion scenario is proposed which involves quick suppression of the turbulent diffusion flame. Classical concept of the thermal explosion is discussed first. Then a possible scenario for the reverse process (thermal implosion) is discussed and illustrated by a relevant mathematical model. Based on the arguments presented in the paper, thermal implosion may be observed as an unstable equilibrium point on the generalized Semenov diagram for turbulent flame, however this hypothesis requires ultimate experimental confirmation.

  2. Applications of zero-suppressed decision diagrams

    CERN Document Server

    Sasao, Tsutomu

    2014-01-01

    A zero-suppressed decision diagram (ZDD) is a data structure to represent objects that typically contain many zeros. Applications include combinatorial problems, such as graphs, circuits, faults, and data mining. This book consists of four chapters on the applications of ZDDs. The first chapter by Alan Mishchenko introduces the ZDD. It compares ZDDs to BDDs, showing why a more compact representation is usually achieved in a ZDD. The focus is on sets of subsets and on sum-of-products (SOP) expressions. Methods to generate all the prime implicants (PIs), and to generate irredundant SOPs are show

  3. Experimental Status Of $J/\\psi$ Suppression

    CERN Document Server

    Kluberg, L; Alessandro, B; Alexa, C; Arnaldi, R; Astruc, J; Atayan, M; Baglin, C; Baldit, A; Bedjidian, M; Bellaiche, F; Beolè, S; Boldea, V; Bordalo, P; Bussière, A; Capelli,L; Capony, V; Casagrande, L; Castor, J; Chambon, T; Chaurand, B; Chevrot, I; Cheynis, B; Chiavassa, E; Cicalò, C; Comets, M P; Constans, N; Constantinescu, S; Cruz, J; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Ducroux, L; Espagnon, B; Fargeix, J; Filippov, S N; Fleuret, F; Force, P; Gallio, M; Gavrilov, Y K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanyan, H; Hakobyan, R; Haroutunian, R; Idzik, M; Jouan, D; Karavitcheva, T L; Kurepin, A B; Le Bornec, Y; Lourenrço, C; Macciotta, P; Mac Cormick, M; Marzari- Chiesa, A; Masera, M; Masoni, A; Mehrabyan, S; Monteno, M; Mourgues, S; Musso, A; Ohlsson-Malek, F; Petiau, P; Piccotti, A; Pizzi, J R; Prado da Silva, W L; Puddu, G; Quintans, C; Racca, C; Ramello, L; Ramos, S; Rato-Mendes, P; Riccati, L; Romana, A; Ropotar, I; Saturnini, P; Scomparin, E; Serci, S; Shahoyan, R; Silva, S; Sitta, M; Soave, C; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N

    2001-01-01

    The most recent results obtained by experiment NA50 show that the $J /\\psi$ cross-section per nucleon-nucleon collision in semi-peripheral Pb-Pb reactions is "normally" suppressed in the sense that it follows the trend already observed from p-p and up to the most central S-U reactions. A clear change of behaviour is observed for more central Pb-Pb collisions which could be due to the transition of normal nuclear matter to its predicted Quark-Gluon Plasma state

  4. Improved attractants for enhancing tsetse fly suppression

    International Nuclear Information System (INIS)

    2003-09-01

    At the initiation of this co-ordinated research project (CRP), the available visually attractant devices and odours for entomological monitoring and for suppression of tsetse fly populations were not equally effective against all economically important tsetse fly species. For species like G. austeni, G. brevipalpis, G. swynnertoni and some species of the PALPALIS-group of tsetse flies no sufficiently effective combinations of visual or odour attractants were available for efficient suppression and standardized monitoring as part of an operational integrated intervention campaign against the tsetse and trypanosomosis (T and T) problem. The Co-ordinated Research Project on Improved Attractants for Enhancing the Efficiency of Tsetse Fly Suppression Operations and Barrier Systems used in Tsetse Control/Eradication Campaigns involved (a) the identification, synthesis and provision of candidate kairomones, their analogues and of dispensers; (b) laboratory screening of synthesised candidate kairomones through electrophysiological studies and wind tunnel experiments; (c) field tests of candidate kairomones alone or as part of odour blends, in combination with available and or new trap designs; and (d) analysis of hydrocarbons that influence tsetse sexual behaviour. The CRP accomplished several main objectives, namely: - The screening of new structurally related compounds, including specific stereoisomers, of known tsetse attractants resulted in the identification of several new candidate odour attractants with promising potential. - An efficient two-step synthetic method was developed for the pilot plant scale production of 3-n-propyphenol, synergistic tsetse kairomone component. - Electrophysiological experiments complemented with wind tunnel studies provided an efficient basis for the laboratory screening of candidate attractants prior to the initiation of laborious field tests. - New traps were identified and modifications of existing traps were tested for some species

  5. Pressure suppression system for a nuclear reactor

    International Nuclear Information System (INIS)

    Jost, N.

    1977-01-01

    The invention pertains to a pressure suppression system for PWR reactors where the parts enclosing the primary coolant are contained in two pressure-tight separate chambers. According to the invention, these chambers are partly filled with water and are connected with each other below the water surface. This way, gases cannot escape from the containment, not even if a valve and a line are damaged at the same time, as the vapours released condensate in the water of at least one of the other chambers. (HP) [de

  6. Fractional order absolute vibration suppression (AVS) controllers

    Science.gov (United States)

    Halevi, Yoram

    2017-04-01

    Absolute vibration suppression (AVS) is a control method for flexible structures. The first step is an accurate, infinite dimension, transfer function (TF), from actuation to measurement. This leads to the collocated, rate feedback AVS controller that in some cases completely eliminates the vibration. In case of the 1D wave equation, the TF consists of pure time delays and low order rational terms, and the AVS controller is rational. In all other cases, the TF and consequently the controller are fractional order in both the delays and the "rational parts". The paper considers stability, performance and actual implementation in such cases.

  7. The relation of weight suppression and BMI to bulimic symptoms.

    Science.gov (United States)

    Butryn, Meghan L; Juarascio, Adrienne; Lowe, Michael R

    2011-11-01

    High levels of weight suppression have been associated with greater binge eating and weight gain as well as poorer treatment outcome in bulimia nervosa. This study examined the relationship between weight suppression and bulimia nervosa symptoms and explored how weight suppression might interact with body mass index (BMI) in accounting for level of symptomatology at presentation for treatment. Participants were 64 women with threshold or sub-threshold bulimia nervosa. A clinical interview assessed binge eating and purging. Weight suppression and the interaction between BMI and weight suppression predicted frequency of binge eating such that participants with low BMI and high weight suppression engaged in the most binge eating. High levels of weight suppression also predicted more frequent purging. Additional research is warranted to examine mediators of these relationships. Copyright © 2010 Wiley Periodicals, Inc.

  8. Suppressed Alpha Oscillations Predict Intelligibility of Speech and its Acoustic Details

    Science.gov (United States)

    Weisz, Nathan

    2012-01-01

    Modulations of human alpha oscillations (8–13 Hz) accompany many cognitive processes, but their functional role in auditory perception has proven elusive: Do oscillatory dynamics of alpha reflect acoustic details of the speech signal and are they indicative of comprehension success? Acoustically presented words were degraded in acoustic envelope and spectrum in an orthogonal design, and electroencephalogram responses in the frequency domain were analyzed in 24 participants, who rated word comprehensibility after each trial. First, the alpha power suppression during and after a degraded word depended monotonically on spectral and, to a lesser extent, envelope detail. The magnitude of this alpha suppression exhibited an additional and independent influence on later comprehension ratings. Second, source localization of alpha suppression yielded superior parietal, prefrontal, as well as anterior temporal brain areas. Third, multivariate classification of the time–frequency pattern across participants showed that patterns of late posterior alpha power allowed best for above-chance classification of word intelligibility. Results suggest that both magnitude and topography of late alpha suppression in response to single words can indicate a listener's sensitivity to acoustic features and the ability to comprehend speech under adverse listening conditions. PMID:22100354

  9. Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson's disease.

    Science.gov (United States)

    Joundi, Raed A; Brittain, John-Stuart; Green, Alex L; Aziz, Tipu Z; Brown, Peter; Jenkinson, Ned

    2013-03-01

    The function of synchronous oscillatory activity at beta band (15-30Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. We recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson's disease during a synchronized tapping task at three different externally cued rates. Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping, These findings implicate consistent beta suppression in the facilitation of continuous movement sequences. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

    Directory of Open Access Journals (Sweden)

    Masako Isokawa

    2016-01-01

    Full Text Available GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition, mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

  11. Are local filters blind to provenance? Ant seed predation suppresses exotic plants more than natives

    Science.gov (United States)

    Dean E. Pearson; Nadia S. Icasatti; Jose L. Hierro; Benjamin J. Bird

    2014-01-01

    The question of whether species' origins influence invasion outcomes has been a point of substantial debate in invasion ecology. Theoretically, colonization outcomes can be predicted based on how species' traits interact with community filters, a process presumably blind to species' origins. Yet, exotic plant introductions commonly result in monospecific...

  12. Global and Local Loss Suppression in the UA9 Crystal Collimation Experiment

    CERN Document Server

    Montesano, S

    2012-01-01

    UA9 was operated in the CERN-SPS for some years in view of investigating the feasibility of the halo collimation assisted by bent crystals. Silicon crystals 2 mm long with bending angles of about 150 μrad are used as primary collimators. The crystal collimation process is obtained consistently through channeling with high efficiency. The loss profiles in the area of the crystal collimator setup and in the downstream dispersion suppressor area show a steady reduction of slightly less than one order of magnitude at the onset of the channeling process. This result holds both for protons and for lead ions. The corresponding loss map in the accelerator ring is accordingly reduced. These observations strongly support our expectation that the coherent deflection of the beam halo by a bent crystal should enhance the collimation efficiency in hadron colliders, such as LHC.

  13. PSEUDOMONAS AERUGINOSA BIOFILM INFECTION SUPPRESSES LOCAL HOST RESPONSE IN BURN WOUNDS

    DEFF Research Database (Denmark)

    Trostrup, H.; Lerche, C. J.; Christophersen, L.

    2015-01-01

    Introduction: Non-invasive monitoring of wound healing is warranted. Opticalcoherence tomography (OCT) enables instant visualization of the epidermis andupper dermis. We have studied the healing of uniform epidermal wounds inhumans using OCT. Methods: Thirty-two, 16 females and 16 males, non-smok...

  14. Reinstatement of Conditioned Suppression in Mice

    Directory of Open Access Journals (Sweden)

    Trinette Dirikx

    2006-03-01

    Full Text Available Return of fear after successful exposure therapy calls for a better understanding of the mechanisms of relapse. Classical conditioning research provides a useful framework for conceptualising the acquisition, extinction and reappearance of fear. The present paper focuses on reinstatement, the return of extinguished conditioned responses due to the experience of one or more unconditioned stimuli (USs after extinction. This phenomenon illustrates that unpredictable USs can lead to a return of fear after successful exposure. The data we present is one of the first demonstrations that conditioned suppression of instrumental behaviour can be used as an index of classical conditioning in laboratory mice. The procedure proves to be a promising instrument for assessing fear in mice, both in the context of research aimed at unravelling the functional characteristics of learning and memory in healthy mice and in the context of research aimed at unravelling the neurobiological substrate of psychiatric disorders, e.g., in studies with transgenic and knockout mice. Using this procedure, we report the first observation of reinstatement of conditioned suppression in this species.

  15. Suppressive and immunoprotective functions of Tregs

    Directory of Open Access Journals (Sweden)

    Pushpa ePandiyan

    2011-11-01

    Full Text Available CD4+CD25+Foxp3+ T lymphocytes, known as regulatory T cells or Tregs, have been proposed to be a lineage of professional immune suppressive cells that exclusively counteract the effects of the immunoprotective "helper" and "cytotoxic" lineages of T lymphocytes. Here we discuss new concepts on the mechanisms and functions of Tregs. There are several key points we emphasize: 1. Tregs exert suppressive effects both directly on effector T cells and indirectly through antigen-presenting cells (APCs; 2. Regulation can occur through a novel mechanism of cytokine consumption to regulate as opposed to the usual mechanism of cytokine/chemokine production; 3. In cases where CD4+ effector T cells are directly inhibited by Tregs, it is chiefly through a mechanism of lymphokine withdrawal apoptosis leading to polyclonal deletion (PCD; and 4. Contrary to the current view, we discuss new evidence that Tregs, similar to other T cells lineages, can promote protective immune responses in certain infectious contexts (Pandiyan et al. 2011; Chen et al 2011. Although these points are at variance to varying degrees with the standard model of Treg behavior, we will recount developing findings that support these new concepts.

  16. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  17. Optimal digital filtering for tremor suppression.

    Science.gov (United States)

    Gonzalez, J G; Heredia, E A; Rahman, T; Barner, K E; Arce, G R

    2000-05-01

    Remote manually operated tasks such as those found in teleoperation, virtual reality, or joystick-based computer access, require the generation of an intermediate electrical signal which is transmitted to the controlled subsystem (robot arm, virtual environment, or a cursor in a computer screen). When human movements are distorted, for instance, by tremor, performance can be improved by digitally filtering the intermediate signal before it reaches the controlled device. This paper introduces a novel tremor filtering framework in which digital equalizers are optimally designed through pursuit tracking task experiments. Due to inherent properties of the man-machine system, the design of tremor suppression equalizers presents two serious problems: 1) performance criteria leading to optimizations that minimize mean-squared error are not efficient for tremor elimination and 2) movement signals show ill-conditioned autocorrelation matrices, which often result in useless or unstable solutions. To address these problems, a new performance indicator in the context of tremor is introduced, and the optimal equalizer according to this new criterion is developed. Ill-conditioning of the autocorrelation matrix is overcome using a novel method which we call pulled-optimization. Experiments performed with artificially induced vibrations and a subject with Parkinson's disease show significant improvement in performance. Additional results, along with MATLAB source code of the algorithms, and a customizable demo for PC joysticks, are available on the Internet at http:¿tremor-suppression.com.

  18. Tagging and suppression of pileup jets

    CERN Document Server

    The ATLAS collaboration

    2014-01-01

    The suppression of pileup jets has been a crucial component of many physics analyses using 2012 LHC proton-proton collisions. In ATLAS, tracking information has been used to calculate a variable called the jet-vertex-fraction, which is the fraction of the total mo- mentum of tracks in the jet which is associated to the primary vertex. Imposing a minimum on this variable rejects the majority of pileup jets, but leads to hard-scatter jet efficiencies that depend on the number of reconstructed primary vertices in the event ($N_{Vtx}$). In this note, new track-based variables to suppress pileup jets are developed in such a way that the resulting hard-scatter jet efficiency is stable as a function of $N_{Vtx}$. A multivariate combina- tion of two such variables called the jet-vertex-tagger is constructed. In addition, it is shown that jet-vertex association can be applied to large-R jets, providing a track-based grooming technique that is as powerful as calorimeter-based trimming but based on complementary trackin...

  19. Wireless Inductive Power Device Suppresses Blade Vibrations

    Science.gov (United States)

    Morrison, Carlos R.; Provenza, Andrew J.; Choi, Benjamin B.; Bakhle, Milind A.; Min, James B.; Stefko, George L.; Duffy, Kirsten P.; Fougers, Alan J.

    2011-01-01

    Vibration in turbomachinery can cause blade failures and leads to the use of heavier, thicker blades that result in lower aerodynamic efficiency and increased noise. Metal and/or composite fatigue in the blades of jet engines has resulted in blade destruction and loss of lives. Techniques for suppressing low-frequency blade vibration, such as gtuned circuit resistive dissipation of vibratory energy, h or simply "passive damping," can require electronics incorporating coils of unwieldy dimensions and adding unwanted weight to the rotor. Other approaches, using vibration-dampening devices or damping material, could add undesirable weight to the blades or hub, making them less efficient. A wireless inductive power device (WIPD) was designed, fabricated, and developed for use in the NASA Glenn's "Dynamic Spin Rig" (DSR) facility. The DSR is used to simulate the functionality of turbomachinery. The relatively small and lightweight device [10 lb (approx.=4.5 kg)] replaces the existing venerable and bulky slip-ring. The goal is the eventual integration of this technology into actual turbomachinery such as jet engines or electric power generators, wherein the device will facilitate the suppression of potentially destructive vibrations in fan blades. This technology obviates slip rings, which require cooling and can prove unreliable or be problematic over time. The WIPD consists of two parts: a remote element, which is positioned on the rotor and provides up to 100 W of electrical power to thin, lightweight piezoelectric patches strategically placed on/in fan blades; and a stationary base unit that wirelessly communicates with the remote unit. The base unit supplies inductive power, and also acts as an input and output corridor for wireless measurement, and active control command to the remote unit. Efficient engine operation necessitates minimal disturbance to the gas flow across the turbine blades in any effort to moderate blade vibration. This innovation makes it

  20. Local duality for 2-dimensional local ring

    Indian Academy of Sciences (India)

    dimensional complete local ring whose residue field is an n-dimensional local field in the sense of. Kato–Parshin. Our results generalize the Saito works in the case n = 0 and are applied to study the Bloch–Ogus complex for such rings in various cases.

  1. Local food and tourism

    DEFF Research Database (Denmark)

    Boesen, Morten; Sundbo, Donna; Sundbo, Jon

    2017-01-01

    This article investigates the question: Why local food networks succeed or fail in collaborating with local tourism actors to create more tourism based on local food? The article focuses on entrepreneurial local food networks and their collaboration with local tourism actors. Emphasis...... is on the actions and attitude logics of local food networks and tourism actors, and whether their respective logics fit as a factor to explain why or why not development of local food concepts lead to increased local tourism. Six local food networks and their collaboration with local tourism actors are studied...... by using observation supplemented with other qualitative methods. Analysis of these networks reveals that successful collaboration is characterised by the food networks and tourism actors having at least one logic in common. The fitting logics that lead to success are primarily celebrity and civic logics...

  2. Contribution of suppression difficulty and lessons learned in forecasting fire suppression operations productivity: A methodological approach

    Science.gov (United States)

    Francisco Rodríguez y Silva; Armando González-Cabán

    2016-01-01

    We propose an economic analysis using utility and productivity, and efficiency theories to provide fire managers a decision support tool to determine the most efficient fire management programs levels. By incorporating managers’ accumulated fire suppression experiences (capitalized experience) in the analysis we help fire managers...

  3. Perceptual grouping without awareness: superiority of Kanizsa triangle in breaking interocular suppression.

    Directory of Open Access Journals (Sweden)

    Lan Wang

    Full Text Available Much information could be processed unconsciously. However, there is no direct evidence on whether perceptual grouping could occur without awareness. To answer this question, we investigated whether a Kanizsa triangle (an example of perceptual grouping is processed differently from stimuli with the same local components but are ungrouped or weakly grouped. Specifically, using a suppression time paradigm we tested whether a Kanizsa triangle would emerge from interocular continuous flash suppression sooner than control stimuli. Results show a significant advantage of the Kanizsa triangle: the Kanizsa triangle emerged from suppression noise significantly faster than the control stimulus with the local Pacmen randomly rotated (t(9 = -2.78, p = 0.02; and also faster than the control stimulus with all Pacmen rotated 180° (t(11 = -3.20, p<0.01. Additional results demonstrated that the advantage of the grouped Kanizsa triangle could not be accounted for by the faster detection speed at the conscious level for the Kanizsa figures on a dynamic noise background. Our results indicate that certain properties supporting perceptual grouping could be processed in the absence of awareness.

  4. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.

    Directory of Open Access Journals (Sweden)

    Ron Firestein

    2008-04-01

    Full Text Available Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD(+-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR, a diet that broadly suppresses cancer in mammals. Here we show that CR induces a two-fold increase SIRT1 expression in the intestine of rodents and that ectopic induction of SIRT1 in a beta-catenin-driven mouse model of colon cancer significantly reduces tumor formation, proliferation, and animal morbidity in the absence of CR. We show that SIRT1 deacetylates beta-catenin and suppresses its ability to activate transcription and drive cell proliferation. Moreover, SIRT1 promotes cytoplasmic localization of the otherwise nuclear-localized oncogenic form of beta-catenin. Consistent with this, a significant inverse correlation was found between the presence of nuclear SIRT1 and the oncogenic form of beta-catenin in 81 human colon tumor specimens analyzed. Taken together, these observations show that SIRT1 suppresses intestinal tumor formation in vivo and raise the prospect that therapies targeting SIRT1 may be of clinical use in beta-catenin-driven malignancies.

  5. Defining local food

    DEFF Research Database (Denmark)

    Eriksen, Safania Normann

    2013-01-01

    Despite evolving local food research, there is no consistent definition of “local food.” Various understandings are utilized, which have resulted in a diverse landscape of meaning. The main purpose of this paper is to examine how researchers within the local food systems literature define local...... food, and how these definitions can be used as a starting point to identify a new taxonomy of local food based on three domains of proximity....

  6. Improved optical properties of InAs quantum dots for intermediate band solar cells by suppression of misfit strain relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Xie, H. [Department of Physics, Arizona State University, Tempe, Arizona 85287-1504 (United States); School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, Arizona 85287-6106 (United States); Prioli, R. [Department of Physics, Arizona State University, Tempe, Arizona 85287-1504 (United States); Departamento de Física, Pontificia Universidade Católica do Rio de Janeiro, Marques de São Vicente 225, Rio de Janeiro 22452-900 RJ (Brazil); Fischer, A. M.; Ponce, F. A., E-mail: ponce@asu.edu [Department of Physics, Arizona State University, Tempe, Arizona 85287-1504 (United States); Kawabata, R. M. S.; Pinto, L. D.; Souza, P. L. [LabSem, CETUC, Pontificia Universidade Católica do Rio de Janeiro, Marques de São Vicente 225, Rio de Janeiro 22452-900 RJ (Brazil); Instituto Nacional de Ciência e Tecnologia de Nanodispositivos Semicondutores – DISSE – PUC-Rio, RJ (Brazil); Jakomin, R. [Instituto Nacional de Ciência e Tecnologia de Nanodispositivos Semicondutores – DISSE – PUC-Rio, RJ (Brazil); Campus de Xerem, UFRJ, Duque de Caxias-RJ (Brazil); Pires, M. P. [Instituto Nacional de Ciência e Tecnologia de Nanodispositivos Semicondutores – DISSE – PUC-Rio, RJ (Brazil); Instituto de Física, UFRJ, Rio de Janeiro-RJ (Brazil)

    2016-07-21

    The properties of InAs quantum dots (QDs) have been studied for application in intermediate band solar cells. It is found that suppression of plastic relaxation in the QDs has a significant effect on the optoelectronic properties. Partial capping plus annealing is shown to be effective in controlling the height of the QDs and in suppressing plastic relaxation. A force balancing model is used to explain the relationship between plastic relaxation and QD height. A strong luminescence has been observed from strained QDs, indicating the presence of localized states in the desired energy range. No luminescence has been observed from plastically relaxed QDs.

  7. Local perturbations perturb—exponentially–locally

    International Nuclear Information System (INIS)

    De Roeck, W.; Schütz, M.

    2015-01-01

    We elaborate on the principle that for gapped quantum spin systems with local interaction, “local perturbations [in the Hamiltonian] perturb locally [the groundstate].” This principle was established by Bachmann et al. [Commun. Math. Phys. 309, 835–871 (2012)], relying on the “spectral flow technique” or “quasi-adiabatic continuation” [M. B. Hastings, Phys. Rev. B 69, 104431 (2004)] to obtain locality estimates with sub-exponential decay in the distance to the spatial support of the perturbation. We use ideas of Hamza et al. [J. Math. Phys. 50, 095213 (2009)] to obtain similarly a transformation between gapped eigenvectors and their perturbations that is local with exponential decay. This allows to improve locality bounds on the effect of perturbations on the low lying states in certain gapped models with a unique “bulk ground state” or “topological quantum order.” We also give some estimate on the exponential decay of correlations in models with impurities where some relevant correlations decay faster than one would naively infer from the global gap of the system, as one also expects in disordered systems with a localized groundstate

  8. Vibration phenomena in large scale pressure suppression tests

    International Nuclear Information System (INIS)

    Aust, E.; Boettcher, G.; Kolb, M.; Sattler, P.; Vollbrandt, J.

    1982-01-01

    Structure und fluid vibration phenomena (acceleration, strain; pressure, level) were observed during blow-down experiments simulating a LOCA in the GKSS full scale multivent pressure suppression test facility. The paper describes first the source related excitations during the two regimes of condensation oscillation and of chugging, and deals then with the response vibrations of the facility's wetwell. Modal analyses of the wetwell were run using excitation by hammer and by shaker in order to separate phenomena that are particular to the GKSS facility from more general ones, i.e. phenomena specific to the fluid related parameters of blowdown and to the geometry of the vent pipes only. The lowest periodicities at about 12 and 16 Hz stem from the vent acoustics. A frequency of about 36 to 38 Hz prominent during chugging seems to result from the lowest local models of two of the wetwell's walls when coupled by the wetwell pool. Further peaks found during blowdown in the spectra of signals at higher frequencies correspond to global vibration modes of the wetwell. (orig.)

  9. New model. Local financing for local energy

    International Nuclear Information System (INIS)

    Detroy, Florent

    2015-01-01

    While evoking the case of the VMH Energies company in the Poitou-Charentes region, and indicating the difference between France and Germany in terms of wind and photovoltaic energy production potential, of number of existing local companies, and of citizen-based funding, this article shows that renewable energies could put the energy production financing in France into question again, with a more important participation of local communities and of their inhabitants. The author describes how the law on energy transition makes this possible, notably with the strengthening of citizen participation. The author evokes some French local experiments and the case of Germany where this participation is already very much developed

  10. Overview of systemic and localized amyloidosis

    Directory of Open Access Journals (Sweden)

    Saulius Girnius

    2013-10-01

    Full Text Available Amyloidosis is a family of protein misfolding disorders, in which insoluble fibrillar proteins deposit extracellularly and cause end organ damage. Depending on the precursor protein, clinical manifestations in amyloidosis vary significantly. In systemic amyloidosis, the heart, kidneys, and nerves are most commonly affected, resulting in congestive heart failure, arrhythmia, nephrotic syndrome, renal failure, and peripheral and autonomic neuropathies. In localized amyloidosis, amyloid deposits at the site of production, so only one organ is disrupted. Once amyloidosis is confirmed histologically, the precursor subtype must be identified using immunohistochemistry, immunofixation, electron microscopy, or laser microdissection and mass spectrometry. Treatment should not be initiated prior to the identification of the type of amyloidosis. Currently, treatment focuses on the suppression of the precursor protein: in AL amyloidosis, chemotherapy or autologous stem cell transplants suppress production of immunoglobulin light chains; in AA amyloidosis, anti-microbial and anti-inflammatory agents suppress amyloid A production; and in AF amyloidosis, a liver transplantation removes the source of mutant transthyretin protein production. Newer drugs are being developed to target amyloidosis at an epigenetic level or stabilize folding intermediates, but there are currently in development.http://dx.doi.org/10.7175/rhc.v4i4.662

  11. Antiviral RNA silencing suppression activity of Tomato spotted wilt virus NSs protein.

    Science.gov (United States)

    Ocampo Ocampo, T; Gabriel Peralta, S M; Bacheller, N; Uiterwaal, S; Knapp, A; Hennen, A; Ochoa-Martinez, D L; Garcia-Ruiz, H

    2016-06-17

    In addition to regulating gene expression, RNA silencing is an essential antiviral defense system in plants. Triggered by double-stranded RNA, silencing results in degradation or translational repression of target transcripts. Viruses are inducers and targets of RNA silencing. To condition susceptibility, most plant viruses encode silencing suppressors that interfere with this process, such as the Tomato spotted wilt virus (TSWV) NSs protein. The mechanism by which NSs suppresses RNA silencing and its role in viral infection and movement remain to be determined. We cloned NSs from the Hawaii isolate of TSWV and using two independent assays show for the first time that this protein restored pathogenicity and supported the formation of local infection foci by suppressor-deficient Turnip mosaic virus and Turnip crinkle virus. Demonstrating the suppression of RNA silencing directed against heterologous viruses establishes the foundation to determine the means used by NSs to block this antiviral process.

  12. ELM suppression in low edge collisionality H-mode discharges using n = 3 magnetic perturbations

    Energy Technology Data Exchange (ETDEWEB)

    Burrell, K H [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Evans, T E [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Doyle, E J [University of California, Los Angeles, California (United States); Fenstermacher, M E [Lawrence Livermore National Laboratory, Livermore, California (United States); Groebner, R J [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Leonard, A W [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Moyer, R A [University of California, San Diego, California (United States); Osborne, T H; Schaffer, M J; Snyder, P B [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Thomas, P R [CEA Cadarache EURATOM Association, Cadarache (France); West, W P [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Boedo, J A [University of California, San Diego, California (United States); Garofalo, A M [Columbia University, New York, New York (United States); Gohil, P; Jackson, G L; La Haye, R J [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Lasnier, C J [Lawrence Livermore National Laboratory, Livermore, California (United States); Reimerdes, H [Columbia University, New York, New York (United States); Rhodes, T L [University of California, Los Angeles, California (United States); Scoville, J T [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Solomon, W M [Princeton Plasma Physics Laboratory, Princeton, New Jersey (United States); Thomas, D M [General Atomics, PO Box 85608, San Diego, CA 92186-9784 (United States); Wang, G [University of California, Los Angeles, California (United States); Watkins, J G [Sandia National Laboratories, Albuquerque, New Mexico (United States); Zeng, L [University of California, Los Angeles, California (United States)

    2005-12-15

    Using resonant magnetic perturbations with toroidal mode number n = 3, we have produced H-mode discharges without edge localized modes (ELMs) which run with constant density and radiated power for periods up to about 2550 ms (17 energy confinement times). These ELM suppression results are achieved at pedestal collisionalities close to those desired for next step burning plasma experiments such as ITER and provide a means of eliminating the rapid erosion of divertor components in such machines which could be caused by giant ELMs. The ELM suppression is due to an enhancement in the edge particle transport which reduces pedestal current density and maximum edge pressure gradient below the threshold for peeling-ballooning modes. These n = 3 magnetic perturbations provide a means of active control of edge plasma transport.

  13. ZNF307, a novel zinc finger gene suppresses p53 and p21 pathway

    International Nuclear Information System (INIS)

    Li Jing; Wang Yuequn; Fan Xiongwei; Mo Xiaoyang; Wang Zequn; Li Yongqing; Yin Zhaochu; Deng Yun; Luo Na; Zhu Chuanbing; Liu Mingyao; Ma Qian; Ocorr, Karen; Yuan Wuzhou; Wu Xiushan

    2007-01-01

    We have cloned a novel KRAB-related zinc finger gene, ZNF307, encoding a protein of 545 aa. ZNF307 is conserved across species in evolution and is differentially expressed in human adult and fetal tissues. The fusion protein of EGFP-ZNF307 localizes in the nucleus. Transcriptional activity assays show ZNF307 suppresses transcriptional activity of L8G5-luciferase. Overexpressing ZNF307 in different cell lines also inhibits the transcriptional activities of p53 and p21. Moreover, ZNF307 works by reducing the p53 protein level and p53 protein reduction is achieved by increasing transcription of MDM2 and EP300. ZNF307 might suppress p53-p21 pathway through activating MDM2 and EP300 expression and inducing p53 degradation

  14. ELM suppression in low edge collisionality H-mode discharges using n = 3 magnetic perturbations

    International Nuclear Information System (INIS)

    Burrell, K H; Evans, T E; Doyle, E J; Fenstermacher, M E; Groebner, R J; Leonard, A W; Moyer, R A; Osborne, T H; Schaffer, M J; Snyder, P B; Thomas, P R; West, W P; Boedo, J A; Garofalo, A M; Gohil, P; Jackson, G L; La Haye, R J; Lasnier, C J; Reimerdes, H; Rhodes, T L; Scoville, J T; Solomon, W M; Thomas, D M; Wang, G; Watkins, J G; Zeng, L

    2005-01-01

    Using resonant magnetic perturbations with toroidal mode number n = 3, we have produced H-mode discharges without edge localized modes (ELMs) which run with constant density and radiated power for periods up to about 2550 ms (17 energy confinement times). These ELM suppression results are achieved at pedestal collisionalities close to those desired for next step burning plasma experiments such as ITER and provide a means of eliminating the rapid erosion of divertor components in such machines which could be caused by giant ELMs. The ELM suppression is due to an enhancement in the edge particle transport which reduces pedestal current density and maximum edge pressure gradient below the threshold for peeling-ballooning modes. These n = 3 magnetic perturbations provide a means of active control of edge plasma transport

  15. The generation and suppression of synchrotron sidebands

    International Nuclear Information System (INIS)

    Warren, R.W.; Goldstein, J.C.

    1987-01-01

    Computer simulations of FEL lasing differ in the degree to which they approximate real experiments. One of the FEL codes used extensively at Los Alamos takes account of the features of each electron micropulse and follows the growth and saturation of the optical micropulse. With no additional adjustments, this code displays the development of sidebands and demonstrates their control when optical filters of various kinds are used. Other codes that do not include a description of the micropulse do not automatically display sidebands but need to have artificial noise of some kind added. This is not unexpected because sidebands are generated by an FEL instability; instabilities, in general, need some kind of initiating disturbance. In this paper we: identify the disturbance that triggers the instability in the pulse code; discuss a practical way to suppress the instability without using filters; compare these results with experiments; and discuss these findings. 22 refs., 9 figs

  16. Probe suppression in conformal phased array

    CERN Document Server

    Singh, Hema; Neethu, P S

    2017-01-01

    This book considers a cylindrical phased array with microstrip patch antenna elements and half-wavelength dipole antenna elements. The effect of platform and mutual coupling effect is included in the analysis. The non-planar geometry is tackled by using Euler's transformation towards the calculation of array manifold. Results are presented for both conducting and dielectric cylinder. The optimal weights obtained are used to generate adapted pattern according to a given signal scenario. It is shown that array along with adaptive algorithm is able to cater to an arbitrary signal environment even when the platform effect and mutual coupling is taken into account. This book provides a step-by-step approach for analyzing the probe suppression in non-planar geometry. Its detailed illustrations and analysis will be a useful text for graduate and research students, scientists and engineers working in the area of phased arrays, low-observables and stealth technology.

  17. Obtuse triangle suppression in anisotropic meshes

    KAUST Repository

    Sun, Feng; Choi, Yi King; Wang, Wen Ping; Yan, Dongming; Liu, Yang; Lé vy, Bruno L.

    2011-01-01

    Anisotropic triangle meshes are used for efficient approximation of surfaces and flow data in finite element analysis, and in these applications it is desirable to have as few obtuse triangles as possible to reduce the discretization error. We present a variational approach to suppressing obtuse triangles in anisotropic meshes. Specifically, we introduce a hexagonal Minkowski metric, which is sensitive to triangle orientation, to give a new formulation of the centroidal Voronoi tessellation (CVT) method. Furthermore, we prove several relevant properties of the CVT method with the newly introduced metric. Experiments show that our algorithm produces anisotropic meshes with much fewer obtuse triangles than using existing methods while maintaining mesh anisotropy. © 2011 Elsevier B.V. All rights reserved.

  18. Void growth suppression by dislocation impurity atmospheres

    International Nuclear Information System (INIS)

    Weertman, J.; Green, W.V.

    1976-01-01

    A detailed calculation is given of the effect of an impurity atmosphere on void growth under irradiation damage conditions. Norris has proposed that such an atmosphere can suppress void growth. The hydrostatic stress field of a dislocation that is surrounded by an impurity atmosphere was found and used to calculate the change in the effective radius of a dislocation line as a sink for interstitials and vacancies. The calculation of the impurity concentration in a Cottrell cloud takes into account the change in hydrostatic pressure produced by the presence of the cloud itself. It is found that void growth is eliminated whenever dislocations are surrounded by a condensed atmosphere of either oversized substitutional impurity atoms or interstitial impurity atoms. A condensed atmosphere will form whenever the average impurity concentration is larger than a critical concentration

  19. In-beam background suppression shield

    DEFF Research Database (Denmark)

    Santoro, V.; Cai, Xiao Xiao; DiJulio, D. D.

    2015-01-01

    The long (3 ms) proton pulse of the European Spallation Source (ESS) gives rise to unique and potentially high backgrounds for the instrument suite. In such a source an instrument's capabilities will be limited by its Signal to Noise (S/N) ratio. The instruments with a direct view of the moderator......, which do not use a bender to help mitigate the fast neutron background, are the most challenging. For these beam lines we propose the innovative shielding of placing blocks of material directly into the guide system, which allow a minimum attenuation of the cold and thermal fluxes relative...... to the background suppression. This shielding configuration has been worked into a beam line model using Geant4. We study particularly the advantages of single crystal sapphire and silicon blocks....

  20. Suppression of fertility in adult cats

    DEFF Research Database (Denmark)

    Goericke-Pesch, Sandra Kathrin; Wehrend, A.; Georgiev, P.

    2014-01-01

    /needed? (iii) sex of the animal? New effective and available methods for hormonal contraception include melatonin implants for short-term post ponement of oestrus in adult queens and slow-release GnRH-agonist implants containing deslorelin (Suprelorin®) for short- and long-term contraception in male and female......Contents: Cats are animals with highly efficient reproduction, clearly pointing to a need for suppression of fertility. Although surgical contraception is highly effective, it is not always the method of choice. This is predominantly because it is cost-intensive, time-consuming and irreversible......, with the latter being of major importance for cat breeders. This article reviews the use of progestins, scleroting agents, immunocontraception, melatonin, GnRH antagonists and finally, GnRH agonists, in adult male and female cats in detail, according to the present state of the art. By now, various scientific...

  1. Suppression of coffee ring: (Particle) size matters

    Science.gov (United States)

    Bansal, Lalit; Seth, Pranjal; Murugappan, Bhubesh; Basu, Saptarshi

    2018-05-01

    Coffee ring patterns in drying sessile droplets are undesirable in various practical applications. Here, we experimentally demonstrate that on hydrophobic substrates, the coffee ring can be suppressed just by increasing the particle diameter. Particles with larger size flocculate within the evaporation timescale, leading to a significant gravimetric settling (for Pe > 1) triggering a uniform deposit. Interestingly, the transition to a uniform deposit is found to be independent of the internal flow field and substrate properties. Flocculation of particles also alters the particle packing at the nanoscale resulting in order to disorder transitions. In this letter, we exhibit a physical exposition on how particle size affects morphodynamics of the droplet drying at macro-nano length scales.

  2. Obtuse triangle suppression in anisotropic meshes

    KAUST Repository

    Sun, Feng

    2011-12-01

    Anisotropic triangle meshes are used for efficient approximation of surfaces and flow data in finite element analysis, and in these applications it is desirable to have as few obtuse triangles as possible to reduce the discretization error. We present a variational approach to suppressing obtuse triangles in anisotropic meshes. Specifically, we introduce a hexagonal Minkowski metric, which is sensitive to triangle orientation, to give a new formulation of the centroidal Voronoi tessellation (CVT) method. Furthermore, we prove several relevant properties of the CVT method with the newly introduced metric. Experiments show that our algorithm produces anisotropic meshes with much fewer obtuse triangles than using existing methods while maintaining mesh anisotropy. © 2011 Elsevier B.V. All rights reserved.

  3. Are Patents used to Suppress Useful Technology?

    DEFF Research Database (Denmark)

    Howells, John

    2006-01-01

    of innovation, other than in the trivial sense of excluding third parties from the right to develop the technology covered by the patent? There are many references to this possibility in the management, economic and legal literatures, but two highly-cited papers stand out for grounding their claims of corporate......This article examines the evidence behind claims that innovation is hindered or blocked (termed technology suppression) by corporations' use of patents. In other words, are there ways in which the exploitation of the exclusive development right of the patent can be shown to retard the process...... and the difference between economic monopoly and an exclusive right. It is argued here that what is at issue in this work is the proper function of the patent institution. It is shown early in this paper that the understanding of the patent institution as a system of development prospects makes better sense...

  4. Active vibration suppression of helicopter horizontal stabilizers

    Science.gov (United States)

    Cinquemani, Simone; Cazzulani, Gabriele; Resta, Ferruccio

    2017-04-01

    Helicopters are among the most complex machines ever made. While ensuring high performance from the aeronautical point of view, they are not very comfortable due to vibration mainly created by the main rotor and by the interaction with the surrounding air. One of the most solicited structural elements of the vehicle are the horizontal stabilizers. These elements are particularly stressed because of their composite structure which, while guaranteeing lightness and strength, is characterized by a low damping. This work makes a preliminary analysis on the dynamics of the structure and proposes different solutions to actively suppress vibrations. Among them, the best in terms of the relationship between performance and weight / complexity of the system is that based on inertial actuators mounted on the inside of the horizontal stabilizers. The work addresses the issue of the design of the device and its use in the stabilizer from both the numerical and the experimental points of view.

  5. Ion suppression from blood collection devices

    DEFF Research Database (Denmark)

    Hasselstrøm, Jørgen Bo; Sejr Gothelf, Aase

    The aim of the study was to examine the variation in ion suppression in ultra high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS-MS) methods when using different blood collection devices. Three different methods measuring 18 antidepressants and antipsychotics in total were...... Terumo, S-monovette from Sarstedt, Vacuette from Greiner Bio-One and three BD Vacutainer serum tubes from BD. These seven different blood collection devices were used to withdraw blood from five healthy drug free donors (n=35) in random order. The samples were centrifuged and serum from each sample...... by UHPLC-MS-MS using three different gradients (Group I, II and III). The analytes in group I was measured on an Agilent 6460 mass spectrometer and group II and III were measured on an Agilent 6410 mass spectrometer both utilizing positive electrospray ionization. The experiments demonstrated significant...

  6. Neutrino wave function and oscillation suppression

    International Nuclear Information System (INIS)

    Dolgov, A.D.; Lychkovskiy, O.V.; Mamonov, A.A.; Okun, L.B.; Schepkin, M.G.

    2005-01-01

    We consider a thought experiment, in which a neutrino is produced by an electron on a nucleus in a crystal. The wave function of the oscillating neutrino is calculated assuming that the electron is described by a wave packet. If the electron is relativistic and the spatial size of its wave packet is much larger than the size of the crystal cell, then the wave packet of the produced neutrino has essentially the same size as the wave packet of the electron. We investigate the suppression of neutrino oscillations at large distances caused by two mechanisms: (1) spatial separation of wave packets corresponding to different neutrino masses; (2) neutrino energy dispersion for given neutrino mass eigenstates. We resolve the contributions of these two mechanisms. (orig.)

  7. Thought Suppression Research Methods: Paradigms, Theories, Methodological Concerns

    Directory of Open Access Journals (Sweden)

    Niczyporuk Aneta

    2016-12-01

    Full Text Available It is hard to provide an unequivocal answer to the question of whether or not thought suppression is effective. Two thought suppression paradigms - the “white bear” paradigm and the think/no-think paradigm - give mixed results. Generally, “white bear” experiments indicate that thought suppression is counterproductive, while experiments in the think/no-think paradigm suggest that it is possible to effectively suppress a thought. There are also alternative methods used to study thought suppression, for instance the directed forgetting paradigm or the Stroop task. In the article, I describe the research methods used to explore thought suppression efficacy. I focus on the “white bear” and the think/no-think paradigms and discuss theories proposed to explain the results obtained. I also consider the internal and external validity of the methods used.

  8. Suppressive effects of ketamine on macrophage functions

    International Nuclear Information System (INIS)

    Chang Yi; Chen, T.-L.; Sheu, J.-R.; Chen, R.-M.

    2005-01-01

    Ketamine is an intravenous anesthetic agent. Clinically, induction of anesthesia with ketamine can cause immunosuppression. Macrophages play important roles in host defense. In this study, we attempted to evaluate the effects of ketamine on macrophage functions and its possible mechanism using mouse macrophage-like Raw 264.7 cells as the experimental model. Exposure of macrophages to 10 and 100 μM ketamine, which correspond to 0.1 and 1 times the clinically relevant concentration, for 1, 6, and 24 h had no effect on cell viability or lactate dehydrogenase release. When the administered concentration reached 1000 μM, ketamine caused a release of lactate dehydrogenase and cell death. Ketamine, at 10 and 100 μM, did not affect the chemotactic activity of macrophages. Administration of 1000 μM ketamine in macrophages resulted in a decrease in cell migration. Treatment of macrophages with ketamine reduced phagocytic activities. The oxidative ability of macrophages was suppressed by ketamine. Treatment with lipopolysaccharide induced TNF-α, IL-1β, and IL-6 mRNA in macrophages. Administration of ketamine alone did not influence TNF-α, IL-1β, or IL-6 mRNA production. Meanwhile, cotreatment with ketamine and lipopolysaccharide significantly inhibited lipopolysaccharide-induced TNF-α, IL-1β, and IL-6 mRNA levels. Exposure to ketamine led to a decrease in the mitochondrial membrane potential. However, the activity of mitochondrial complex I NADH dehydrogenase was not affected by ketamine. This study shows that a clinically relevant concentration of ketamine (100 μM) can suppress macrophage function of phagocytosis, its oxidative ability, and inflammatory cytokine production possibly via reduction of the mitochondrial membrane potential instead of direct cellular toxicity

  9. Rituximab selectively suppresses specific islet antibodies.

    Science.gov (United States)

    Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

    2011-10-01

    The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.

  10. Suppression of soil nitrification by plants.

    Science.gov (United States)

    Subbarao, Guntur Venkata; Yoshihashi, Tadashi; Worthington, Margaret; Nakahara, Kazuhiko; Ando, Yasuo; Sahrawat, Kanwar Lal; Rao, Idupulapati Madhusudhana; Lata, Jean-Christophe; Kishii, Masahiro; Braun, Hans-Joachim

    2015-04-01

    Nitrification, the biological oxidation of ammonium to nitrate, weakens the soil's ability to retain N and facilitates N-losses from production agriculture through nitrate-leaching and denitrification. This process has a profound influence on what form of mineral-N is absorbed, used by plants, and retained in the soil, or lost to the environment, which in turn affects N-cycling, N-use efficiency (NUE) and ecosystem health and services. As reactive-N is often the most limiting in natural ecosystems, plants have acquired a range of mechanisms that suppress soil-nitrifier activity to limit N-losses via N-leaching and denitrification. Plants' ability to produce and release nitrification inhibitors from roots and suppress soil-nitrifier activity is termed 'biological nitrification inhibition' (BNI). With recent developments in methodology for in-situ measurement of nitrification inhibition, it is now possible to characterize BNI function in plants. This review assesses the current status of our understanding of the production and release of biological nitrification inhibitors (BNIs) and their potential in improving NUE in agriculture. A suite of genetic, soil and environmental factors regulate BNI activity in plants. BNI-function can be genetically exploited to improve the BNI-capacity of major food- and feed-crops to develop next-generation production systems with reduced nitrification and N2O emission rates to benefit both agriculture and the environment. The feasibility of such an approach is discussed based on the progresses made. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Regorafenib suppresses sinusoidal obstruction syndrome in rats.

    Science.gov (United States)

    Okuno, Masayuki; Hatano, Etsuro; Nakamura, Kojiro; Miyagawa-Hayashino, Aya; Kasai, Yosuke; Nishio, Takahiro; Seo, Satoru; Taura, Kojiro; Uemoto, Shinji

    2015-02-01

    Sinusoidal obstruction syndrome (SOS), a form of drug-induced liver injury related to oxaliplatin treatment, is associated with postoperative morbidity after hepatectomy. This study aimed to examine the impact of regorafenib, the first small-molecule kinase inhibitor to show efficacy against metastatic colorectal cancer, on a rat model of SOS. Rats with monocrotaline (MCT)-induced SOS were divided into two groups according to treatment with either regorafenib (6 mg/kg) or vehicle alone, which were administered at 12 and 36 h, respectively, before MCT administration. Histopathologic examination and serum biochemistry tests were performed 48 h after MCT administration. Sinusoidal endothelial cells were evaluated by immunohistochemistry and electron microscopy. To examine whether regorafenib preserved remnant liver function, a 30% hepatectomy was performed in each group. The rats in the vehicle group displayed typical SOS features, whereas these features were suppressed in the regorafenib group. The total SOS scores were significantly lower in the regorafenib group than in the vehicle group. Immunohistochemistry and electron microscopy showed that regorafenib had a protective effect on sinusoidal endothelial cells. The postoperative survival rate after 7 d was significantly better in the regorafenib group than that in the vehicle group (26.7% versus 6.7%, P Regorafenib reduced the phosphorylation of extracellular signal-regulated kinase, which induced matrix metalloproteinase-9 (MMP-9) activation and decreased the activity of MMP-9, one of the crucial mediators of SOS development. Regorafenib suppressed MCT-induced SOS, concomitant with attenuating extracellular signal-regulated kinase phosphorylation, and MMP-9 activation, suggesting that regorafenib may be a favorable agent for use in combination with oxaliplatin-based chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Are Claims of Global Warming Being Suppressed?

    Science.gov (United States)

    Crowley, Thomas J.

    2006-02-01

    Over the last few years, I have heard many rumors that climate science relevant to the global warming discussion is being suppressed by the Bush Administration. One cannot do much about third-hand information. However, on 29 January, the New York Times published a front page article on NASA efforts to suppress statements about global warming by James Hansen, director of the NASA Goddard Institute for Space Studies. A claim by one government scientist, though, no matter how distinguished, still requires examples from other scientists before a general conclusion can be drawn about the overall scope of the problem. But if the charges are more widespread, then some government scientists might be reluctant to make such claims, because they might feel that their positions were jeopardized. Therefore, an alternate way may be needed to determine the scope of the issue, while still safeguarding government workers from possible retaliation. -On 30 January, Rep. Sherwood Boehlert (R-N.Y.), chairman of the U.S. House of Representatives Committee on Science, wrote a letter to NASA Administrator Michael Griffin addressing many of the concerns Crowley has raised. Boehlert wrote,``It ought to go without saying that government scientists must be free to describe their scientific conclusions and the implications of those conclusions to their fellow scientists, policymakers and the general public.'' He continued,``Good science cannot long persist in an atmosphere of intimidation. Political figures ought to be reviewing their public statements to make sure they are consistent with the best available science; scientists should not be reviewing their statements to make sure they are consistent with the current political orthodoxy.'' I commend Rep. Boehlert for his quick and clear statement of the importance of unfettered communication of science. -FRED SPILHAUS, Editor

  13. SUPPRESSION OF STAR FORMATION IN NGC 1266

    Energy Technology Data Exchange (ETDEWEB)

    Alatalo, Katherine; Lanz, Lauranne; Bitsakis, Theodoros; Appleton, Philip N.; Ogle, Patrick M. [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Lacy, Mark; Lonsdale, Carol J. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Nyland, Kristina; Meier, David S. [Physics Department, New Mexico Tech, Socorro, NM 87801 (United States); Cales, Sabrina L. [Department of Astronomy, Faculty of Physical and Mathematical Sciences, Universidad de Concepción, Casilla 160-C, Concepción (Chile); Chang, Philip [Department of Physics, University of Wisconsin—Milwaukee, Milwaukee, WI 53201 (United States); Davis, Timothy A.; De Zeeuw, P. T. [European Southern Observatory, Karl-Schwarzschild-Str. 2, D-85748 Garching (Germany); Martín, Sergio, E-mail: kalatalo@ipac.caltech.edu [Institut de Radioastronomie Millimétrique, 300 Rue de la Piscine, Domaine Universitaire, F-38406 Saint Martin d' Hères (France)

    2015-01-01

    NGC 1266 is a nearby lenticular galaxy that harbors a massive outflow of molecular gas powered by the mechanical energy of an active galactic nucleus (AGN). It has been speculated that such outflows hinder star formation (SF) in their host galaxies, providing a form of feedback to the process of galaxy formation. Previous studies, however, indicated that only jets from extremely rare, high-power quasars or radio galaxies could impart significant feedback on their hosts. Here we present detailed observations of the gas and dust continuum of NGC 1266 at millimeter wavelengths. Our observations show that molecular gas is being driven out of the nuclear region at M-dot {sub out}≈110 M{sub ⊙} yr{sup –1}, of which the vast majority cannot escape the nucleus. Only 2 M {sub ☉} yr{sup –1} is actually capable of escaping the galaxy. Most of the molecular gas that remains is very inefficient at forming stars. The far-infrared emission is dominated by an ultra-compact (≲ 50 pc) source that could either be powered by an AGN or by an ultra-compact starburst. The ratio of the SF surface density (Σ{sub SFR}) to the gas surface density (Σ{sub H{sub 2}}) indicates that SF is suppressed by a factor of ≈50 compared to normal star-forming galaxies if all gas is forming stars, and ≈150 for the outskirt (98%) dense molecular gas if the central region is powered by an ultra-compact starburst. The AGN-driven bulk outflow could account for this extreme suppression by hindering the fragmentation and gravitational collapse necessary to form stars through a process of turbulent injection. This result suggests that even relatively common, low-power AGNs are able to alter the evolution of their host galaxies as their black holes grow onto the M-σ relation.

  14. Sunspot Light Walls Suppressed by Nearby Brightenings

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shuhong; Zhang, Jun; Hou, Yijun; Li, Xiaohong [CAS Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Erdélyi, Robertus [Solar Physics and Space Plasma Research Centre, School of Mathematics and Statistics, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom); Yan, Limei, E-mail: shuhongyang@nao.cas.cn [Key Laboratory of Earth and Planetary Physics, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029 (China)

    2017-07-01

    Light walls, as ensembles of oscillating bright structures rooted in sunspot light bridges, have not been well studied, although they are important for understanding sunspot properties. Using the Interface Region Imaging Spectrograph and Solar Dynamics Observatory observations, here we study the evolution of two oscillating light walls each within its own active region (AR). The emission of each light wall decays greatly after the appearance of adjacent brightenings. For the first light wall, rooted within AR 12565, the average height, amplitude, and oscillation period significantly decrease from 3.5 Mm, 1.7 Mm, and 8.5 minutes to 1.6 Mm, 0.4 Mm, and 3.0 minutes, respectively. For the second light wall, rooted within AR 12597, the mean height, amplitude, and oscillation period of the light wall decrease from 2.1 Mm, 0.5 Mm, and 3.0 minutes to 1.5 Mm, 0.2 Mm, and 2.1 minutes, respectively. Particularly, a part of the second light wall even becomes invisible after the influence of a nearby brightening. These results reveal that the light walls are suppressed by nearby brightenings. Considering the complex magnetic topology in light bridges, we conjecture that the fading of light walls may be caused by a drop in the magnetic pressure, where the flux is canceled by magnetic reconnection at the site of the nearby brightening. Another hypothesis is that the wall fading is due to the suppression of driver source ( p -mode oscillation), resulting from the nearby avalanche of downward particles along reconnected brightening loops.

  15. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates temporal suppression of click-evoked otoacoustic emissions (CEOAEs), occurring when a suppressor-click is presented close in time to a test-click (e.g. 0-8ms). Various temporal suppression methods for examining temporal changes in cochlear compression were evaluated and me...... under test. Temporal suppression was shown to be comparable for CEOAEs and SSOAEs, indicating similar underlying cochlear nonlinear mechanisms. This study contributes to a better understanding of the temporal properties of cochlear dynamics....

  16. Social Hierarchy and Depression: The Role of Emotion Suppression

    OpenAIRE

    Langner, Carrie A.; Epel, Elissa; Matthews, Karen; Moskowitz, Judith T.; Adler, Nancy

    2012-01-01

    Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depre...

  17. Psychophysical research progress of interocular suppression in amblyopic visual system

    OpenAIRE

    Jing-Jing Li; Yi Huang

    2016-01-01

    Some recent animal experiments and psychophysical studies indicate that patients with amblyopia have a structurally intact binocular visual system that is rendered functionally monocular due to suppression, and interocular suppression is a key mechanism in visual deficits experienced by patients with amblyopia. The aim of this review is to provide an overview of recent psychophysical findings that have investigated the important role of interocular suppression in amblyopia, the measurement an...

  18. Binocular vision in amblyopia : structure, suppression and plasticity

    OpenAIRE

    Hess, Robert F; Thompson, Benjamin; Baker, Daniel Hart

    2014-01-01

    The amblyopic visual system was once considered to be structurally monocular. However, it now evident that the capacity for binocular vision is present in many observers with amblyopia. This has led to new techniques for quantifying suppression that have provided insights into the relationship between suppression and the monocular and binocular visual deficits experienced by amblyopes. Furthermore, new treatments are emerging that directly target suppressive interactions within the visual cor...

  19. Locally analytic vectors in representations of locally

    CERN Document Server

    Emerton, Matthew J

    2017-01-01

    The goal of this memoir is to provide the foundations for the locally analytic representation theory that is required in three of the author's other papers on this topic. In the course of writing those papers the author found it useful to adopt a particular point of view on locally analytic representation theory: namely, regarding a locally analytic representation as being the inductive limit of its subspaces of analytic vectors (of various "radii of analyticity"). The author uses the analysis of these subspaces as one of the basic tools in his study of such representations. Thus in this memoir he presents a development of locally analytic representation theory built around this point of view. The author has made a deliberate effort to keep the exposition reasonably self-contained and hopes that this will be of some benefit to the reader.

  20. Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review

    International Nuclear Information System (INIS)

    Sasse, André D; Sasse, Elisa; Carvalho, Albertina M; Macedo, Ligia T

    2012-01-01

    Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity. Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals. Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long-term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy. Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases

  1. Temporal suppression and augmentation of click-evoked otoacoustic emissions

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Harte, James; Dau, Torsten

    2008-01-01

    This study investigates and models temporal suppression of click-evoked otoacoustic emissions (CEOAEs). This suppression-effect is created when a suppressor-click is presented close in time to a test-click. The analysis was carried out for short time-frames of short- and long-latency CEOAEs...... suppression is present in all CEOAEs for inter-click intervals (ICIs) less than 8 ms. The long-latency CEOAEs showed augmentation (i.e., negative suppression) for ICIs of 6-7 ms which was not reported for the short-latency CEOAE at these ICIs. A phenomenological approach is adopted here to explain both...

  2. Electronic Warfare: Comprehensive Strategy Needed for Suppressing Enemy Air Defenses

    National Research Council Canada - National Science Library

    2001-01-01

    .... To achieve this suppression, the services use specialized aircraft designed to neutralize, destroy, or temporarily degrade enemy air defense systems through either physical attack or electronic warfare...

  3. Disease Suppressive Soils: New Insights from the Soil Microbiome.

    Science.gov (United States)

    Schlatter, Daniel; Kinkel, Linda; Thomashow, Linda; Weller, David; Paulitz, Timothy

    2017-11-01

    Soils suppressive to soilborne pathogens have been identified worldwide for almost 60 years and attributed mainly to suppressive or antagonistic microorganisms. Rather than identifying, testing and applying potential biocontrol agents in an inundative fashion, research into suppressive soils has attempted to understand how indigenous microbiomes can reduce disease, even in the presence of the pathogen, susceptible host, and favorable environment. Recent advances in next-generation sequencing of microbiomes have provided new tools to reexamine and further characterize the nature of these soils. Two general types of suppression have been described: specific and general suppression, and theories have been developed around these two models. In this review, we will present three examples of currently-studied model systems with features representative of specific and general suppressiveness: suppression to take-all (Gaeumannomyces graminis var. tritici), Rhizoctonia bare patch of wheat (Rhizoctonia solani AG-8), and Streptomyces. To compare and contrast the two models of general versus specific suppression, we propose a number of hypotheses about the nature and ecology of microbial populations and communities of suppressive soils. We outline the potential and limitations of new molecular techniques that can provide novel ways of testing these hypotheses. Finally, we consider how this greater understanding of the phytobiome can facilitate sustainable disease management in agriculture by harnessing the potential of indigenous soil microbes.

  4. Double suppression of FCNCs in a supersymmetric model

    International Nuclear Information System (INIS)

    Kajiyama, Yuji

    2004-01-01

    A concrete model which can suppress FCNCs and CP violating phenomena is suggested. It is S 3 symmetric extension of MSSM in extra dimensions where only SU(2) and SU(3) gauge multiplet are assumed to propagate in the bulk. They are suppressed due to S 3 flavor symmetry at M SUSY , and the infrared attractive force of gauge interaction in extra dimensions are used to suppress them at the compactification scale. We find that O(1) disorders of the soft parameters are allowed at the cut-off scale to suppress FCNCs and CP violating phenomena. (author)

  5. Double suppression of FCNCs in a supersymmetric model

    Energy Technology Data Exchange (ETDEWEB)

    Kajiyama, Yuji [Kanazawa Univ., Dept. of Physics, Kanazawa, Ishikawa (Japan)

    2004-12-01

    A concrete model which can suppress FCNCs and CP violating phenomena is suggested. It is S{sub 3} symmetric extension of MSSM in extra dimensions where only SU(2) and SU(3) gauge multiplet are assumed to propagate in the bulk. They are suppressed due to S{sub 3} flavor symmetry at M{sub SUSY}, and the infrared attractive force of gauge interaction in extra dimensions are used to suppress them at the compactification scale. We find that O(1) disorders of the soft parameters are allowed at the cut-off scale to suppress FCNCs and CP violating phenomena. (author)

  6. The regional extent of suppression: strabismics versus nonstrabismics.

    Science.gov (United States)

    Babu, Raiju Jacob; Clavagnier, Simon R; Bobier, William; Thompson, Benjamin; Hess, Robert F

    2013-10-09

    Evidence is accumulating that suppression may be the cause of amblyopia rather than a secondary consequence of mismatched retinal images. For example, treatment interventions that target suppression may lead to better binocular and monocular outcomes. Furthermore, it has recently been demonstrated that the measurement of suppression may have prognostic value for patching therapy. For these reasons, the measurement of suppression in the clinic needs to be improved beyond the methods that are currently available, which provide a binary outcome. We describe a novel quantitative method for measuring the regional extent of suppression that is suitable for clinical use. The method involves a dichoptic perceptual matching procedure at multiple visual field locations. We compare a group of normal controls (mean age: 28 ± 5 years); a group with strabismic amblyopia (four with microesotropia, five with esotropia, and one with exotropia; mean age: 35 ± 10 years); and a group with nonstrabismic anisometropic amblyopia (mean age: 33 ± 12 years). The extent and magnitude of suppression was similar for observers with strabismic and nonstrabismic amblyopia. Suppression was strongest within the central field and extended throughout the 20° field that we measured. Suppression extends throughout the central visual field in both strabismic and anisometropic forms of amblyopia. The strongest suppression occurs within the region of the visual field corresponding to the fovea of the fixing eye.

  7. Active Neural Localization

    OpenAIRE

    Chaplot, Devendra Singh; Parisotto, Emilio; Salakhutdinov, Ruslan

    2018-01-01

    Localization is the problem of estimating the location of an autonomous agent from an observation and a map of the environment. Traditional methods of localization, which filter the belief based on the observations, are sub-optimal in the number of steps required, as they do not decide the actions taken by the agent. We propose "Active Neural Localizer", a fully differentiable neural network that learns to localize accurately and efficiently. The proposed model incorporates ideas of tradition...

  8. Representative of local committee

    International Nuclear Information System (INIS)

    Barcelo, C.

    2007-01-01

    Carlos Barcelo, spoke about the involvement of local companies in the dismantling project. Local companies realised that they could not undertake the whole project, and informed ENRESA of the tasks in which they would be able to co-operate. On the whole, during the course of the 5-year project the local and regional firms were given more work than they had originally expected. Mr. Barcelo praised the good partnership that evolved between the local firms and the implementer. (author)

  9. Local network assessment

    Science.gov (United States)

    Glen, D. V.

    1985-04-01

    Local networks, related standards activities of the Institute of Electrical and Electronics Engineers the American National Standards Institute and other elements are presented. These elements include: (1) technology choices such as topology, transmission media, and access protocols; (2) descriptions of standards for the 802 local area networks (LAN's); high speed local networks (HSLN's) and military specification local networks; and (3) intra- and internetworking using bridges and gateways with protocols Interconnection (OSI) reference model. The convergence of LAN/PBX technology is also described.

  10. Unconscious Local Motion Alters Global Image Speed

    Science.gov (United States)

    Khuu, Sieu K.; Chung, Charles Y. L.; Lord, Stephanie; Pearson, Joel

    2014-01-01

    Accurate motion perception of self and object speed is crucial for successful interaction in the world. The context in which we make such speed judgments has a profound effect on their accuracy. Misperceptions of motion speed caused by the context can have drastic consequences in real world situations, but they also reveal much about the underlying mechanisms of motion perception. Here we show that motion signals suppressed from awareness can warp simultaneous conscious speed perception. In Experiment 1, we measured global speed discrimination thresholds using an annulus of 8 local Gabor elements. We show that physically removing local elements from the array attenuated global speed discrimination. However, removing awareness of the local elements only had a small effect on speed discrimination. That is, unconscious local motion elements contributed to global conscious speed perception. In Experiment 2 we measured the global speed of the moving Gabor patterns, when half the elements moved at different speeds. We show that global speed averaging occurred regardless of whether local elements were removed from awareness, such that the speed of invisible elements continued to be averaged together with the visible elements to determine the global speed. These data suggest that contextual motion signals outside of awareness can both boost and affect our experience of motion speed, and suggest that such pooling of motion signals occurs before the conscious extraction of the surround motion speed. PMID:25503603

  11. Breaking continuous flash suppression: A new measure of unconscious processing during interocular suppression?

    Directory of Open Access Journals (Sweden)

    Timo eStein

    2011-12-01

    Full Text Available Until recently, it has been thought that under interocular suppression high-level visual processing is strongly inhibited if not abolished. With the development of continuous flash suppression (CFS, a variant of binocular rivalry, this notion has now been challenged by a number of reports showing that even high-level aspects of visual stimuli, such as familiarity, affect the time stimuli need to overcome CFS and emerge into awareness. In this breaking CFS (b-CFS paradigm, differential unconscious processing during suppression is inferred when (a speeded detection responses to initially invisible stimuli differ, and (b no comparable differences are found in non-rivalrous control conditions supposed to measure general threshold differences between stimuli. To critically evaluate these assumptions was the aim of the present study. In six experiments we compared the time upright and inverted faces needed to be detected. We found that not only under CFS, but also in control conditions upright faces were detected faster and more accurately than inverted faces, although the effect was larger during CFS. However, reaction time (RT distributions indicated critical differences between the CFS and the control condition. When RT distributions were matched, similar effect sizes were obtained in both conditions. Moreover, subjective ratings revealed that CFS and control conditions are not perceptually comparable. These findings cast doubt on the usefulness of non-rivalrous control conditions to rule out mere detection threshold differences as a cause of shorter detection latencies during CFS. In conclusion, we acknowledge that the b-CFS paradigm can be fruitfully applied as a highly sensitive device to probe differences between stimuli in their potency to gain access to awareness. However, our current findings suggest that such differences can not unequivocally be attributed to differential unconscious processing under interocular suppression.

  12. Suppress to feel and remember less: Neural correlates of explicit and implicit emotional suppression on perception and memory.

    Science.gov (United States)

    Katsumi, Yuta; Dolcos, Sanda

    2018-02-09

    Available evidence suggests that emotion regulation can modulate both immediate (emotional experience) and long-term (episodic memory) effects of emotion, and that both explicit and implicit forms may be effective. However, neural mechanisms by which explicit and implicit emotional suppression affect these phenomena remain unclear, particularly regarding their effects on memory. In this study, participants rated the emotional content of negative and neutral images, following explicit (verbal instructions) or implicit (priming) induction of emotional suppression goals, during functional magnetic resonance imaging. Participants' memory for the images was tested one week later. Behaviorally, explicit suppression reduced emotional ratings of negative images, whereas both explicit and implicit suppression reduced subsequent memory. At the neural level, the engagement of explicit suppression was uniquely associated with decreased activity in the amygdala (AMY), during emotional ratings, and in the AMY and inferior frontal gyrus (IFG), during successful encoding. Although both explicit and implicit suppression diminished functional connectivity between these regions and the hippocampus (HC) linked to successful encoding, explicit suppression was uniquely associated with interference with AMY-HC interactions, which no longer predicted subsequent memory for the explicitly-suppressed items. Overall, these findings advance our understanding of the common and dissociable mechanisms of explicit and implicit emotional suppression on perception and memory, and suggest their impact on both bottom-up and top-down mechanisms involved in emotion-cognition interactions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Elevated extracellular potassium ion concentrations suppress ...

    African Journals Online (AJOL)

    To address this question, we examined how elevations of [K+]o affect hippocampal oscillations in Scn1a mutant mouse, a mouse model of Dravet syndrome, a devastating genetic-epilepsy associated with gliosis, a major cause of dysregulated K+ homeostasis in epileptic brain. Methods: To this end, performing local field ...

  14. Effects of lesions of the dorsal noradrenergic bundle on conditioned suppression to a CS and to a contextual background stimulus.

    Science.gov (United States)

    Tsaltas, E; Schugens, M M; Gray, J A

    1989-01-01

    The aim of the experiment was to determine whether the dorsal noradrenergic bundle (DB) plays a role in conditioning to context. Rats received either bilateral lesions of the DB by local injection of 6-hydroxydopamine, vehicle injections only, or sham operations. All animals were then trained to barpress for food on a variable interval (VI) schedule. Two 5-min intrusion periods were superimposed on the VI baseline during each session. An 'envelope' stimulus (flashing light) was on throughout each intrusion period. In addition, embedded in the two intrusion periods of each session, there occurred 8 presentations of a 'punctate' conditioned stimulus (CS) (a 15-s clicker), and 8 presentations of a 0.5-s footshock. Within each surgical condition rats were randomly allocated to one of three conditioning groups, receiving 100%, 50% or 0% temporal association between CS and shock. Conditioning to the punctate CS and to the context provided by the envelope stimulus was assessed by the degree of suppression of the barpress response relative to the VI baseline. Responding was most suppressed in the punctate CS in the 100 and 50% conditions, and most suppressed in the envelope stimulus in the 0% condition. DB lesions released response suppression to the punctate CS, had no effect on suppression to the envelope stimulus, and reduced sensitivity to CS-shock probability as measured by response suppression during the punctate CS. These results confirm previous reports that DB lesions alleviate response suppression to shock-associated cues, identify some of the parameters that affect this phenomenon, but fail to support a role for the DB in contextual conditioning.

  15. Validation of the model for ELM suppression with 3D magnetic fields using low torque ITER baseline scenario discharges in DIII-D

    Science.gov (United States)

    Moyer, R. A.; Paz-Soldan, C.; Nazikian, R.; Orlov, D. M.; Ferraro, N. M.; Grierson, B. A.; Knölker, M.; Lyons, B. C.; McKee, G. R.; Osborne, T. H.; Rhodes, T. L.; Meneghini, O.; Smith, S.; Evans, T. E.; Fenstermacher, M. E.; Groebner, R. J.; Hanson, J. M.; La Haye, R. J.; Luce, T. C.; Mordijck, S.; Solomon, W. M.; Turco, F.; Yan, Z.; Zeng, L.; DIII-D Team

    2017-10-01

    Experiments have been executed in the DIII-D tokamak to extend suppression of Edge Localized Modes (ELMs) with Resonant Magnetic Perturbations (RMPs) to ITER-relevant levels of beam torque. The results support the hypothesis for RMP ELM suppression based on transition from an ideal screened response to a tearing response at a resonant surface that prevents expansion of the pedestal to an unstable width [Snyder et al., Nucl. Fusion 51, 103016 (2011) and Wade et al., Nucl. Fusion 55, 023002 (2015)]. In ITER baseline plasmas with I/aB = 1.4 and pedestal ν * ˜ 0.15, ELMs are readily suppressed with co- I p neutral beam injection. However, reducing the beam torque from 5 Nm to ≤ 3.5 Nm results in loss of ELM suppression and a shift in the zero-crossing of the electron perpendicular rotation ω ⊥ e ˜ 0 deeper into the plasma. The change in radius of ω ⊥ e ˜ 0 is due primarily to changes to the electron diamagnetic rotation frequency ωe * . Linear plasma response modeling with the resistive MHD code m3d-c1 indicates that the tearing response location tracks the inward shift in ω ⊥ e ˜ 0. At pedestal ν * ˜ 1, ELM suppression is also lost when the beam torque is reduced, but the ω ⊥ e change is dominated by collapse of the toroidal rotation v T . The hypothesis predicts that it should be possible to obtain ELM suppression at reduced beam torque by also reducing the height and width of the ωe * profile. This prediction has been confirmed experimentally with RMP ELM suppression at 0 Nm of beam torque and plasma normalized pressure β N ˜ 0.7. This opens the possibility of accessing ELM suppression in low torque ITER baseline plasmas by establishing suppression at low beta and then increasing beta while relying on the strong RMP-island coupling to maintain suppression.

  16. Theoretical Study of the Vibration Suppression on a Mistuned Bladed Disk Using a Bi-periodic Piezoelectric Network

    Science.gov (United States)

    Li, Lin; Deng, Pengcheng; Liu, Jiuzhou; Li, Chao

    2018-03-01

    The paper deals with the vibration suppression of a bladed disk with a piezoelectric network. The piezoelectric network has a different period (so called bi-period) from that of the bladed disk and there is no inductor in it. The system is simulated by an electromechanical lumped parameter model with two DOFs per sector. The research focuses on suppressing the amplitude magnification or reducing the vibration localization of the mistuned bladed disk. The dynamic equations of the system are derived. Both mechanical mistuning and electrical mistuning have been taken into account. The Modified Modal Assurance Criterion (MMAC) is used to evaluate the vibration suppression ability of the bi-periodic piezoelectric network. The Monte Carlo simulation is used to calculate the MMAC of the system with the random mistuning. As a reference, the forced responses of the bladed disk with and without the piezoelectric network are given. The results show that the piezoelectric network would effectively suppress amplitude magnification induced by mistuning. The vibration amplitude is even smaller than that of the tuned system. The robustness analysis shows that the bi-periodic piezoelectric network can provide a reliable assurance for avoiding the forced response amplification of the mistuned bladed disk. The amplified response induced by the mechanical mistuning with standard deviation 0.2 can be effectively suppressed through the bi-periodic piezoelectric network.

  17. High rate of virological re-suppression among patients failing ...

    African Journals Online (AJOL)

    Results. Of 69 patients enrolled in the programme, 40 had at least one follow-up VL and no known drug resistance at enrolment; 27 (68%) of these re-suppressed while remaining on second-line ART following enhanced adherence support. The majority (18/27; 67%) achieved re-suppression within the first 3 months in the ...

  18. Thought Suppression and Meaning in Life: A Longitudinal Investigation

    Science.gov (United States)

    Krause, Neal

    2007-01-01

    The purpose of this study is to see if older adults who experience problems with thought suppression tend to encounter greater difficulty deriving a sense of meaning in life. Data from a longitudinal nationwide survey of older people (N = 988) indicate that greater difficulty with thought suppression is associated with a decline in meaning over…

  19. Dynamic interactions of the cortical networks during thought suppression.

    Science.gov (United States)

    Aso, Toshihiko; Nishimura, Kazuo; Kiyonaka, Takashi; Aoki, Takaaki; Inagawa, Michiyo; Matsuhashi, Masao; Tobinaga, Yoshikazu; Fukuyama, Hidenao

    2016-08-01

    Thought suppression has spurred extensive research in clinical and preclinical fields, particularly with regard to the paradoxical aspects of this behavior. However, the involvement of the brain's inhibitory system in the dynamics underlying the continuous effort to suppress thoughts has yet to be clarified. This study aims to provide a unified perspective for the volitional suppression of internal events incorporating the current understanding of the brain's inhibitory system. Twenty healthy volunteers underwent functional magnetic resonance imaging while they performed thought suppression blocks alternating with visual imagery blocks. The whole dataset was decomposed by group-independent component analysis into 30 components. After discarding noise components, the 20 valid components were subjected to further analysis of their temporal properties including task-relatedness and between-component residual correlation. Combining a long task period and a data-driven approach, we observed a right-side-dominant, lateral frontoparietal network to be strongly suppression related. This network exhibited increased fluctuation during suppression, which is compatible with the well-known difficulty of suppression maintenance. Between-network correlation provided further insight into the coordinated engagement of the executive control and dorsal attention networks, as well as the reciprocal activation of imagery-related components, thus revealing neural substrates associated with the rivalry between intrusive thoughts and the suppression process.

  20. Suppressive mechanisms in visual motion processing: From perception to intelligence.

    Science.gov (United States)

    Tadin, Duje

    2015-10-01

    Perception operates on an immense amount of incoming information that greatly exceeds the brain's processing capacity. Because of this fundamental limitation, the ability to suppress irrelevant information is a key determinant of perceptual efficiency. Here, I will review a series of studies investigating suppressive mechanisms in visual motion processing, namely perceptual suppression of large, background-like motions. These spatial suppression mechanisms are adaptive, operating only when sensory inputs are sufficiently robust to guarantee visibility. Converging correlational and causal evidence links these behavioral results with inhibitory center-surround mechanisms, namely those in cortical area MT. Spatial suppression is abnormally weak in several special populations, including the elderly and individuals with schizophrenia-a deficit that is evidenced by better-than-normal direction discriminations of large moving stimuli. Theoretical work shows that this abnormal weakening of spatial suppression should result in motion segregation deficits, but direct behavioral support of this hypothesis is lacking. Finally, I will argue that the ability to suppress information is a fundamental neural process that applies not only to perception but also to cognition in general. Supporting this argument, I will discuss recent research that shows individual differences in spatial suppression of motion signals strongly predict individual variations in IQ scores. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Burst-Suppression Ratio on Electrocorticography Depends on Interelectrode Distance

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Calin, Alexandru; Kumaraswamy, Vishakhadatta M.

    2016-01-01

    Introduction: With deepening of anesthesia-induced comatose states, the EEG becomes fragmented by increasing periods of suppression. When measured from conventional EEG recordings, the binary burst-suppression signal (BS) appears similar across the scalp. As such, the BS ratio (BSR), quantifying...

  2. Regularized Adaptive Notch Filters for Acoustic Howling Suppression

    DEFF Research Database (Denmark)

    Gil-Cacho, Pepe; van Waterschoot, Toon; Moonen, Marc

    2009-01-01

    In this paper, a method for the suppression of acoustic howling is developed, based on adaptive notch filters (ANF) with regularization (RANF). The method features three RANFs working in parallel to achieve frequency tracking, howling detection and suppression. The ANF-based approach to howling...

  3. Social hierarchy and depression: the role of emotion suppression.

    Science.gov (United States)

    Langner, Carrie A; Epel, Elissa S; Matthews, Karen A; Moskowitz, Judith T; Adler, Nancy E

    2012-01-01

    Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The coronary artery risk development in young adults [CARDIA] study; Cutter et al., 1991). Much as in study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression.

  4. Suppression of mouse-killing in rats following irradiation

    International Nuclear Information System (INIS)

    O'Boyle, M.

    1976-01-01

    Suppression of mouse-killing was produced following pairings of mouse-presentations (CS) with 96 roentgens of ionizing radiation (US) at 0 (less than 2 min.) and 30 min. US-CS interstimulus intervals. No suppression was found at CS-US intervals of 30 min., 1 hr., and 2 hr., or at US-CS intervals of 1 hr. and 2 hr

  5. How best to assess suppression in patients with high anisometropia.

    Science.gov (United States)

    Li, Jinrong; Hess, Robert F; Chan, Lily Y L; Deng, Daming; Chen, Xiang; Yu, Minbin; Thompson, Benjamin S

    2013-02-01

    We have recently described a rapid technique for measuring suppression using a dichoptic signal/noise task. Here, we report a modification of this technique that allows for accurate measurements to be made in amblyopic patients with high levels of anisometropia. This was necessary because aniseikonic image size differences between the two eyes can provide a cue for signal/noise segregation and, therefore, influence suppression measurement in these patients. Suppression was measured using our original technique and with a modified technique whereby the size of the signal and noise elements was randomized across the stimulus to eliminate size differences as a cue for task performance. Eleven patients with anisometropic amblyopia, five with more than 5 diopters (D) spherical equivalent difference (SED), six with less than 5 D SED between the eyes, and 10 control observers completed suppression measurements using both techniques. Suppression measurements in controls and patients with less than 5 D SED were constant across the two techniques; however, patients with more than 5 D SED showed significantly stronger suppression on the modified technique with randomized element size. Measurements made with the modified technique correlated with the loss of visual acuity in the amblyopic eye and were in good agreement with previous reports using detailed psychophysical measurements. The signal/noise technique for measuring suppression can be applied to patients with high levels of anisometropia and aniseikonia if element size is randomized. In addition, deeper suppression is associated with a greater loss of visual acuity in patients with anisometropic amblyopia.

  6. Improved fat suppression of the breast using discretized frequency shimming

    NARCIS (Netherlands)

    van der Velden, Tijl A.; Luijten, Peter R.; Klomp, DWJ

    2018-01-01

    Purpose: Robust fat suppression is essential in bilateral breast MRI at 7 Tesla. The lack of good fat suppression can result in errors when calculating the enhancement curve from dynamic contrast-enhanced acquisitions. In this work we propose discretized frequency shimming to improve the quality of

  7. Continuous Flash Suppression: Stimulus Fractionation rather than Integration.

    Science.gov (United States)

    Moors, Pieter; Hesselmann, Guido; Wagemans, Johan; van Ee, Raymond

    2017-10-01

    Recent studies using continuous flash suppression suggest that invisible stimuli are processed as integrated, semantic entities. We challenge the viability of this account, given recent findings on the neural basis of interocular suppression and replication failures of high-profile CFS studies. We conclude that CFS reveals stimulus fractionation in visual cortex. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Eye Contact Facilitates Awareness of Faces during Interocular Suppression

    Science.gov (United States)

    Stein, Timo; Senju, Atsushi; Peelen, Marius V.; Sterzer, Philipp

    2011-01-01

    Eye contact captures attention and receives prioritized visual processing. Here we asked whether eye contact might be processed outside conscious awareness. Faces with direct and averted gaze were rendered invisible using interocular suppression. In two experiments we found that faces with direct gaze overcame such suppression more rapidly than…

  9. Nature of dynamical suppressions in the generalized Veneziano model

    International Nuclear Information System (INIS)

    Odorico, R.

    1976-05-01

    It is shown by explicit numerical calculations that of a class of coupling suppressions existing in the generalized Veneziano model, which have been recently used to interpret the psi data and other related phenomena, only a part can be attributed to the exponential growth with energy of the number of levels in the model. The remaining suppressions have a more direct dual origin

  10. A dual purpose Compton suppression spectrometer

    CERN Document Server

    Parus, J; Raab, W; Donohue, D

    2003-01-01

    A gamma-ray spectrometer with a passive and an active shield is described. It consists of a HPGe coaxial detector of 42% efficiency and 4 NaI(Tl) detectors. The energy output pulses of the Ge detector are delivered into the 3 spectrometry chains giving the normal, anti- and coincidence spectra. From the spectra of a number of sup 1 sup 3 sup 7 Cs and sup 6 sup 0 Co sources a Compton suppression factor, SF and a Compton reduction factor, RF, as the parameters characterizing the system performance, were calculated as a function of energy and source activity and compared with those given in literature. The natural background is reduced about 8 times in the anticoincidence mode of operation, compared to the normal spectrum which results in decreasing the detection limits for non-coincident gamma-rays up to a factor of 3. In the presence of other gamma-ray activities, in the range from 5 to 11 kBq, non- and coincident, the detection limits can be decreased for some nuclides by a factor of 3 to 5.7.

  11. Is neutrinoless double beta decay suppressed

    International Nuclear Information System (INIS)

    Tomoda, T.

    1989-01-01

    Much effort has been devoted to the study of nuclear double beta decay, since the observation of a neutrinoless double beta (OνΒΒ) decay would be clear evidence that the electron neutrino is a Majorana particle. The OνΒΒ decay is caused by a finite Majorana neutrino mass and/or an admixture of right-handed leptonic currents. In order to relate these quantities to OνΒΒ decay rates, we need nuclear matrix elements, which are model dependent. One of the possibilities of testing nuclear models employed in such analysis is to calculate the experimentally known rates of ΒΒ decay with emission of two neutrinos (2νΒΒ decay) which occurs independently of the nature of the neutrino. There was a long-standing difficulty in such attempts that the calculated 2νΒΒ decay rates turned out to be always too large by one to two orders of magnitude. Trying to overcome such difficulty, Klapdor and Grotz as well as Vogel and Zirnbauer showed in their calculation using schematic effective interactions such that 2νΒΒ decay rates can get reduced considerably due to the nuclear ground state correlations. This paper reports that the suppression is ascribed to that of the virtual Gamow-Teller transitions from the excited 1 + states of the intermediate odd-odd -even nucleus

  12. Myeloma cells suppress osteoblasts through sclerostin secretion

    Energy Technology Data Exchange (ETDEWEB)

    Colucci, S; Brunetti, G; Oranger, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Mori, G [Department of Biomedical Science, University of Foggia, Foggia (Italy); Sardone, F [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Specchia, G; Rinaldi, E; Curci, P; Liso, V [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Passeri, G [Department of Internal Medicine and Biomedical Sciences, Center for Metabolic Bone Diseases, University of Parma, Parma (Italy); Zallone, A [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy); Rizzi, R [Department of Emergency and Organ Transplantation, Hematology Section, Bari University Medical School, Bari (Italy); Grano, M [Department of Human Anatomy and Histology, University of Bari Medical School, Bari (Italy)

    2011-06-01

    Wingless-type (Wnt) signaling through the secretion of Wnt inhibitors Dickkopf1, soluble frizzled-related protein-2 and -3 has a key role in the decreased osteoblast (OB) activity associated with multiple myeloma (MM) bone disease. We provide evidence that another Wnt antagonist, sclerostin, an osteocyte-expressed negative regulator of bone formation, is expressed by myeloma cells, that is, human myeloma cell lines (HMCLs) and plasma cells (CD138+ cells) obtained from the bone marrow (BM) of a large number of MM patients with bone disease. We demonstrated that BM stromal cells (BMSCs), differentiated into OBs and co-cultured with HMCLs showed, compared with BMSCs alone, reduced expression of major osteoblastic-specific proteins, decreased mineralized nodule formation and attenuated the expression of members of the activator protein 1 transcription factor family (Fra-1, Fra-2 and Jun-D). Moreover, in the same co-culture system, the addition of neutralizing anti-sclerostin antibodies restored OB functions by inducing nuclear accumulation of β-catenin. We further demonstrated that the upregulation of receptor activator of nuclear factor κ-B ligand and the downregulation of osteoprotegerin in OBs were also sclerostin mediated. Our data indicated that sclerostin secretion by myeloma cells contribute to the suppression of bone formation in the osteolytic bone disease associated to MM.

  13. Glutamine supplementation suppresses herpes simplex virus reactivation.

    Science.gov (United States)

    Wang, Kening; Hoshino, Yo; Dowdell, Kennichi; Bosch-Marce, Marta; Myers, Timothy G; Sarmiento, Mayra; Pesnicak, Lesley; Krause, Philip R; Cohen, Jeffrey I

    2017-06-30

    Chronic viral infections are difficult to treat, and new approaches are needed, particularly those aimed at reducing reactivation by enhancing immune responses. Herpes simplex virus (HSV) establishes latency and reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and proliferation of activated T cells requires increased metabolism of glutamine. Here, we found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1-infected mice and HSV-2-infected guinea pigs. Transcriptome analysis of trigeminal ganglia from latently HSV-1-infected, glutamine-treated WT mice showed upregulation of several IFN-γ-inducible genes. In contrast to WT mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in latently HSV-1-infected IFN-γ-KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-γ-producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

  14. Installation for the suppression of sodium fires

    International Nuclear Information System (INIS)

    Newman, R.N.; Payne, J.F.B.; Lee, C.J.; Rowe, D.M.J.

    1979-01-01

    The basic operating principles are discussed of a passive baffle-catch tray fire suppression system for sodium fires. A new design is described incorporating increased compartmentalization of the collecting and drainage parts of the device. The burning and smoke generation rates from trays with varying aperture sizes were measured. From the experiments it was found that the burning rate and smoke generation rates could be related satisfactorily to the aperture areas. For the smallest aperture size ( 2 ) it was found that the smoke release was considerably less than that from a fire of the same area, because the smoke deposited on the underside of the baffle. A re-ignition problem was found, where pillars of sodium oxide (wicks) grow upward from the surface of the drained sodium and begin to burn when level with the baffle aperature. From a knowledge of the rate of growth of the wicks, trays may be made sufficiently deep to avoid the problem. Self acting valves were developed which allow the passage of sodium through the aperture and close when drainage is complete. These devices were shown to effect complete extinction of the drained sodium. Using the designs proposed it is possible to construct a system that will reduce the smoke emission from the drained sodium by a factor approaching 10 3 , without the use of valves, or with the self acting valves developed, reduce the emission from the drained sodium to approximately zero. (author)

  15. Rotator cuff injury: fat suppression MR image

    International Nuclear Information System (INIS)

    Won, Jong Yoon; Suh, Jin Suck; Park, Chang Yun; Lee, Yeon Hee; Kim, Yong Soo

    1994-01-01

    We performed the study prospectively to evaluate the advantage of fat suppression MR in the diagnosis of rotator cuff injury. Ten symptomatic patients were studied with both conventional T2WI and FST2WI using chemical shift technique. Each image was analyzed for the assessment of injuries, conspicuity of the lesion, the presence of effusion in subacromical bursae and joint space, and presence of humeral head injury. Arthroscopy was done in 4 patients following MRI. We could made presumptive diagnoses on FSMR as identical as on conventional MR in six cases(1 normal, 2 tendinitis, 2 partial thickness tear, 1 full thickness tear), two of them were confirmed by arthroscopic procedures. Two cases of partial thickness tear proved by arthroscopy were detected on FST2WI, whereas they were considered tendinitis on conventional T2WI. There were another 2 cases who showed tendinitis on FSMR, but normal on conventional T2WI. They, however, were not confirmed by either arthroscopy or surgical procedure. We found the FSMR were superior to conventional T2WI in the conspicuity of lesions and detection of joint effusion and abnormalities on the humeral head. We think FSMR of the shoulder could have significant diagnostic advantages over the conventional spin-echo MR imaging

  16. Probiotics-mediated suppression of cancer.

    Science.gov (United States)

    So, Stephanie S Y; Wan, Murphy L Y; El-Nezami, Hani

    2017-01-01

    Probiotics can be used as an adjuvant for cancer prevention or/and treatment through their abilities to modulate intestinal microbiota and host immune response. Although most of the recent reviews have focused on the potential role of probiotics against colon cancer, only few of them include the probiotic effect on extraintestinal cancers. The present review covers the most important findings from the literature published during the past 20 months (from January 2015 to August 2016) regarding the probiotics-mediated suppression of both gastrointestinal and extraintestinal cancers and the underlying mechanisms. A comprehensive literature search in Pubmed, Science direct and Google scholar databases was conducted to locate all relevant articles that investigated the effect of probiotics on prevention/treatment of both gastrointestinal and extraintestinal cancers. Different mechanisms for the beneficial effects of probiotics against cancer were also discussed, mainly via modulation of gut microbiota which thereby influences host metabolism and immunity. Despite laboratory-based studies having demonstrated encouraging outcomes that probiotics possess antitumor effects, the benefits should not be exaggerated before we get more results from human clinical trials. These are very important before the medical community can accept the use of probiotics as an alternative therapy for cancer control.

  17. Rotator cuff injury: fat suppression MR image

    Energy Technology Data Exchange (ETDEWEB)

    Won, Jong Yoon; Suh, Jin Suck; Park, Chang Yun; Lee, Yeon Hee [Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Yong Soo [Inje University College of Medicine, Busan (Korea, Republic of)

    1994-04-15

    We performed the study prospectively to evaluate the advantage of fat suppression MR in the diagnosis of rotator cuff injury. Ten symptomatic patients were studied with both conventional T2WI and FST2WI using chemical shift technique. Each image was analyzed for the assessment of injuries, conspicuity of the lesion, the presence of effusion in subacromical bursae and joint space, and presence of humeral head injury. Arthroscopy was done in 4 patients following MRI. We could made presumptive diagnoses on FSMR as identical as on conventional MR in six cases(1 normal, 2 tendinitis, 2 partial thickness tear, 1 full thickness tear), two of them were confirmed by arthroscopic procedures. Two cases of partial thickness tear proved by arthroscopy were detected on FST2WI, whereas they were considered tendinitis on conventional T2WI. There were another 2 cases who showed tendinitis on FSMR, but normal on conventional T2WI. They, however, were not confirmed by either arthroscopy or surgical procedure. We found the FSMR were superior to conventional T2WI in the conspicuity of lesions and detection of joint effusion and abnormalities on the humeral head. We think FSMR of the shoulder could have significant diagnostic advantages over the conventional spin-echo MR imaging.

  18. Suppression of PTEN transcription by UVA

    Science.gov (United States)

    Zhao, Baozhong; Ming, Mei; He, Yu-Ying

    2012-01-01

    Although UVA has different physical and biological targets than UVB, the contribution of UVA to skin cancer susceptibility and its molecular basis remain largely unknown. Here we show that chronic UVA radiation suppresses PTEN expression at the mRNA level. Subchronic and acute UVA radiation also down-regulated PTEN in normal human epidermal keratinocytes, skin culture and mouse skin. At the molecular level, chronic UVA radiation decreased the transcriptional activity of the PTEN promoter in a methylation-independent manner, while it had no effect on the protein stability or mRNA stability of PTEN. In contrast, we found that UVA-induced activation of the Ras/ERK/AKT and NF-κB pathways plays an important role in UV-induced PTEN down-regulation. Inhibiting ERK or AKT increases PTEN expression. Our findings may provide unique insights into PTEN down-regulation as a critical component of UVA’s molecular impact during keratinocyte transformation. PMID:23129115

  19. Pressure suppression device for nuclear reactor building

    International Nuclear Information System (INIS)

    Ikegame, Noboru.

    1992-01-01

    In a nuclear reactor building, there are disposed cooling coils connected to an air supply duct at the outside of the building, an air supply blower, an air supply duct having the top end opened, an exhaustion duct having the top end opened and a bypassing pipeline interposed between the exhaustion duct and the air supply duct on the side of the inlet of the cooling coils. In the reactor building, when a radioactive material leakage accident should occur, an isolation valve is closed to isolate the building from the outside. Further, bypassing isolation valve is opened to form a closed cooling circuit by the cooling coils, the air supply blower and the air supply duct, the exhaustion duct and the bypassing pipeline in the reactor building. With such a constitution, since air as the atmosphere in the building is circulated through the closed cooling circuit and cooled by the cooling coils, the temperature is not elevated. Accordingly, since the pressure elevation of the atmosphere in the building is suppressed, the atmosphere containing radioactive materials do not flow out of the building. (I.N.)

  20. Higher-Order-Mode Diagnostics and Suppression in Superconducting Cavities (HOMSC12)

    Science.gov (United States)

    Jones, Roger M.

    2014-01-01

    From the 25th of June through Wednesday lunchtime of the 27th of June 2012 the Cockcroft Institute and ASTeC hosted an ICFA supported mini workshop on Higher-Order-Mode Diagnostics and Suppression in Superconducting Cavities (HOMSC12). The local organizing committee for this international workshop was chaired by S. Buckley (ASTeC/STFC), conference administration by S. Waller (ASTeC/STFC), and the scientific program committee by R.M. Jones (Cockcroft Institute/University of Manchester).

  1. A mechanism for suppression of the CDP-choline pathway during apoptosis

    OpenAIRE

    Morton, Craig C.; Aitchison, Adam J.; Gehrig, Karsten; Ridgway, Neale D.

    2013-01-01

    Inhibition of the CDP-choline pathway during apoptosis restricts the availability of phosphatidylcholine (PtdCho) for assembly of membranes and synthesis of signaling factors. The N-terminal nuclear localization signal (NLS) in CTP:phosphocholine cytidylyltransferase (CCT)α is removed during apoptosis but the caspase(s) involved and the contribution to suppression of the CDP-choline pathway is unresolved. In this study we utilized siRNA silencing of caspases in HEK293 cells and caspase 3-defi...

  2. Exploring genetic suppression interactions on a global scale.

    Science.gov (United States)

    van Leeuwen, Jolanda; Pons, Carles; Mellor, Joseph C; Yamaguchi, Takafumi N; Friesen, Helena; Koschwanez, John; Ušaj, Mojca Mattiazzi; Pechlaner, Maria; Takar, Mehmet; Ušaj, Matej; VanderSluis, Benjamin; Andrusiak, Kerry; Bansal, Pritpal; Baryshnikova, Anastasia; Boone, Claire E; Cao, Jessica; Cote, Atina; Gebbia, Marinella; Horecka, Gene; Horecka, Ira; Kuzmin, Elena; Legro, Nicole; Liang, Wendy; van Lieshout, Natascha; McNee, Margaret; San Luis, Bryan-Joseph; Shaeri, Fatemeh; Shuteriqi, Ermira; Sun, Song; Yang, Lu; Youn, Ji-Young; Yuen, Michael; Costanzo, Michael; Gingras, Anne-Claude; Aloy, Patrick; Oostenbrink, Chris; Murray, Andrew; Graham, Todd R; Myers, Chad L; Andrews, Brenda J; Roth, Frederick P; Boone, Charles

    2016-11-04

    Genetic suppression occurs when the phenotypic defects caused by a mutation in a particular gene are rescued by a mutation in a second gene. To explore the principles of genetic suppression, we examined both literature-curated and unbiased experimental data, involving systematic genetic mapping and whole-genome sequencing, to generate a large-scale suppression network among yeast genes. Most suppression pairs identified novel relationships among functionally related genes, providing new insights into the functional wiring diagram of the cell. In addition to suppressor mutations, we identified frequent secondary mutations,in a subset of genes, that likely cause a delay in the onset of stationary phase, which appears to promote their enrichment within a propagating population. These findings allow us to formulate and quantify general mechanisms of genetic suppression. Copyright © 2016, American Association for the Advancement of Science.

  3. Gonadotropin suppression in men leads to a reduction in claudin-11 at the Sertoli cell tight junction.

    Science.gov (United States)

    McCabe, M J; Tarulli, G A; Laven-Law, G; Matthiesson, K L; Meachem, S J; McLachlan, R I; Dinger, M E; Stanton, P G

    2016-04-01

    Are Sertoli cell tight junctions (TJs) disrupted in men undergoing hormonal contraception? Localization of the key Sertoli cell TJ protein, claudin-11, was markedly disrupted by 8 weeks of gonadotropin suppression, the degree of which was related to the extent of adluminal germ cell suppression. Sertoli cell TJs are vital components of the blood-testis barrier (BTB) that sequester developing adluminal meiotic germ cells and spermatids from the vascular compartment. Claudin-11 knockout mice are infertile; additionally claudin-11 is spatially disrupted in chronically gonadotropin-suppressed rats coincident with a loss of BTB function, and claudin-11 is disorganized in various human testicular disorders. These data support the Sertoli cell TJ as a potential site of hormonal contraceptive action. BTB proteins were assessed by immunohistochemistry (n = 16 samples) and mRNA (n = 18 samples) expression levels in available archived testis tissue from a previous study of 22 men who had undergone 8 weeks of gonadotropin suppression and for whom meiotic and post-meiotic germ cell numbers were available. The gonadotropin suppression regimens were (i) testosterone enanthate (TE) plus the GnRH antagonist, acyline (A); (ii) TE + the progestin, levonorgestrel, (LNG); (iii) TE + LNG + A or (iv) TE + LNG + the 5α-reductase inhibitor, dutasteride (D). A control group consisted of seven additional men, with three archived samples available for this study. Immunohistochemical localization of claudin-11 (TJ) and other junctional type markers [ZO-1 (cytoplasmic plaque), β-catenin (adherens junction), connexin-43 (gap junction), vinculin (ectoplasmic specialization) and β-actin (cytoskeleton)] and quantitative PCR was conducted using matched frozen testis tissue. Claudin-11 formed a continuous staining pattern at the BTB in control men. Regardless of gonadotropin suppression treatment, claudin-11 localization was markedly disrupted and was broadly associated with the extent of meiotic

  4. A bacterial cysteine protease effector protein interferes with photosynthesis to suppress plant innate immune responses.

    Science.gov (United States)

    Rodríguez-Herva, José J; González-Melendi, Pablo; Cuartas-Lanza, Raquel; Antúnez-Lamas, María; Río-Alvarez, Isabel; Li, Ziduo; López-Torrejón, Gema; Díaz, Isabel; Del Pozo, Juan C; Chakravarthy, Suma; Collmer, Alan; Rodríguez-Palenzuela, Pablo; López-Solanilla, Emilia

    2012-05-01

    The bacterial pathogen Pseudomonas syringae pv tomato DC3000 suppresses plant innate immunity with effector proteins injected by a type III secretion system (T3SS). The cysteine protease effector HopN1, which reduces the ability of DC3000 to elicit programmed cell death in non-host tobacco, was found to also suppress the production of defence-associated reactive oxygen species (ROS) and callose when delivered by Pseudomonas fluorescens heterologously expressing a P. syringae T3SS. Purified His(6) -tagged HopN1 was used to identify tomato PsbQ, a member of the oxygen evolving complex of photosystem II (PSII), as an interacting protein. HopN1 localized to chloroplasts and both degraded PsbQ and inhibited PSII activity in chloroplast preparations, whereas a HopN1(D299A) non-catalytic mutant lost these abilities. Gene silencing of NtPsbQ in tobacco compromised ROS production and programmed cell death by DC3000. Our data reveal PsbQ as a contributor to plant immunity responses and a target for pathogen suppression. © 2012 Blackwell Publishing Ltd.

  5. Local quantum thermal susceptibility

    Science.gov (United States)

    de Pasquale, Antonella; Rossini, Davide; Fazio, Rosario; Giovannetti, Vittorio

    2016-09-01

    Thermodynamics relies on the possibility to describe systems composed of a large number of constituents in terms of few macroscopic variables. Its foundations are rooted into the paradigm of statistical mechanics, where thermal properties originate from averaging procedures which smoothen out local details. While undoubtedly successful, elegant and formally correct, this approach carries over an operational problem, namely determining the precision at which such variables are inferred, when technical/practical limitations restrict our capabilities to local probing. Here we introduce the local quantum thermal susceptibility, a quantifier for the best achievable accuracy for temperature estimation via local measurements. Our method relies on basic concepts of quantum estimation theory, providing an operative strategy to address the local thermal response of arbitrary quantum systems at equilibrium. At low temperatures, it highlights the local distinguishability of the ground state from the excited sub-manifolds, thus providing a method to locate quantum phase transitions.

  6. Local quantum thermal susceptibility

    Science.gov (United States)

    De Pasquale, Antonella; Rossini, Davide; Fazio, Rosario; Giovannetti, Vittorio

    2016-01-01

    Thermodynamics relies on the possibility to describe systems composed of a large number of constituents in terms of few macroscopic variables. Its foundations are rooted into the paradigm of statistical mechanics, where thermal properties originate from averaging procedures which smoothen out local details. While undoubtedly successful, elegant and formally correct, this approach carries over an operational problem, namely determining the precision at which such variables are inferred, when technical/practical limitations restrict our capabilities to local probing. Here we introduce the local quantum thermal susceptibility, a quantifier for the best achievable accuracy for temperature estimation via local measurements. Our method relies on basic concepts of quantum estimation theory, providing an operative strategy to address the local thermal response of arbitrary quantum systems at equilibrium. At low temperatures, it highlights the local distinguishability of the ground state from the excited sub-manifolds, thus providing a method to locate quantum phase transitions. PMID:27681458

  7. [Local anaesthesia in ruminants].

    Science.gov (United States)

    Nuss, Karl; Schwarz, Andrea; Ringer, Simone

    2017-06-20

    The use of local anaesthesia in ruminants allows many surgical procedures to be conducted free of pain, efficiently and inexpensively in the field. Local anaesthesia combined with sedation and immobilisation of the animal can replace general anaesthesia for many procedures (e. g. castration, claw amputation). The level of difficulty differs among various local anaesthetic techniques: local infiltration of tissue or anaesthesia of the cornual nerve are easily performed, whereas local anaesthesia of the eye, regional anaesthesia in limbs or anaesthesia for umbilical surgery are more difficult to carry out. This article presents an illustrated overview of the most common local anaesthetic procedures in cattle as well as in small ruminants and serves as a practical guide for veterinarians in the field. In principle, these techniques can likewise be applied in other ruminants or artiodactyls.

  8. Local Worlds of Activation

    DEFF Research Database (Denmark)

    Jacobsson, Kerstin; Hollertz, Katarina; Garsten, Christina

    2017-01-01

    arrangements and the role of private services and actors in service delivery differed significantly too, ranging from strictly market-based forms of governance to classical public administration. The article moreover shows how the different activation approaches were reflected in the radically different usages...... from local politics, established local traditions, patterns of networking and modes of collaborating, as the notion of ‘local words of activation’ intends to capture....

  9. Quantification of local mobilities

    DEFF Research Database (Denmark)

    Zhang, Y. B.

    2018-01-01

    A new method for quantification of mobilities of local recrystallization boundary segments is presented. The quantification is based on microstructures characterized using electron microscopy and on determination of migration velocities and driving forces for local boundary segments. Pure aluminium...... is investigated and the results show that even for a single recrystallization boundary, different boundary segments migrate differently, and the differences can be understood based on variations in mobilities and local deformed microstructures. The present work has important implications for understanding...

  10. Using Correlated Photons to Suppress Background Noise

    Science.gov (United States)

    Jackson, Deborah; Hockney, George; Dowling, Jonathan

    2003-01-01

    A proposed method of suppressing the effect of background noise in an optical communication system would exploit the transmission and reception of correlated photons at the receiver. The method would not afford any advantage in a system in which performance is limited by shot noise. However, if the performance of the system is limited by background noise (e.g., sunlight in the case of a free-space optical communication system or incoherently scattered in-band photons in the case of a fiber-optic communication system), then the proposed method could offer an advantage: the proposed method would make it possible to achieve a signal-to-noise ratio (S/N) significantly greater than that of an otherwise equivalent background- noise-limited optical communication system based on the classical transmission and reception of uncorrelated photons. The figure schematically depicts a classical optical-communication system and a system according to the proposed method. In the classical system, a modulated laser beam is transmitted along an optical path to a receiver, the optics of which include a narrow-band-pass filter that suppresses some of the background noise. A photodetector in the receiver detects the laser-beam and background photons, most or all of which are uncorrelated. In the proposed system, correlated photons would be generated at the transmitter by making a modulated laser beam pass through a nonlinear parametric down-conversion crystal. The sum of frequencies of the correlated photons in each pair would equal the frequency of the incident photon from which they were generated. As in the classical system, the correlated photons would travel along an optical path to a receiver, where they would be band-pass filtered and detected. Unlike in the classical system, the photodetector in the receiver in this system would be one that intrinsically favors the detection of pairs of correlated photons over the detection of uncorrelated photons. Even though there would be no

  11. Insecticides suppress natural enemies and increase pest damage in cabbage.

    Science.gov (United States)

    Bommarco, Riccardo; Miranda, Freddy; Bylund, Helena; Björkman, Christer

    2011-06-01

    Intensive use of pesticides is common and increasing despite a growing and historically well documented awareness of the costs and hazards. The benefits from pesticides of increased yields from sufficient pest control may be outweighed by developed resistance in pests and killing of beneficial natural enemies. Other negative effects are human health problems and lower prices because of consumers' desire to buy organic products. Few studies have examined these trade-offs in the field. Here, we demonstrate that Nicaraguan cabbage (Brassica spp.) farmers may suffer economically by using insecticides as they get more damage by the main pest diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), at the same time as they spend economic resources on insecticides. Replicated similarly sized cabbage fields cultivated in a standardized manner were either treated with insecticides according common practice or not treated with insecticides over two seasons. Fields treated with insecticides suffered, compared with nontreated fields, equal or, at least in some periods of the seasons, higher diamondback moth pest attacks. These fields also had increased leaf damage on the harvested cabbage heads. Weight and size of the heads were not affected. The farmers received the same price on the local market irrespective of insecticide use. Rates of parasitized diamondback moth were consistently lower in the treated fields. Negative effects of using insecticides against diamondback moth were found for the density of parasitoids and generalist predatory wasps, and tended to affect spiders negatively. The observed increased leaf damages in insecticide-treated fields may be a combined consequence of insecticide resistance in the pest, and of lower predation and parasitization rates from naturally occurring predators that are suppressed by the insecticide applications. The results indicate biological control as a viable and economic alternative pest management strategy

  12. Localization strategy for magnetic resonance coronary angiography

    International Nuclear Information System (INIS)

    Cheng Liuquan; Gao Yuangui; Sun Wei; Sheng Fugeng; Cai Youquan

    2003-01-01

    Objective: To develop a localization strategy for magnetic resonance coronary angiography (MRCA). Methods: In 89 subjects, the standard 4-chamber view and long-axis view of left and right ventricle were acquired using Fast-Imaging-Employing-Steady-State-Acquisition (FIESTA) sequence in CINE mode, and the trigger-delay time for mid-diastolic phase was determined. Coronary vessels including right coronary artery (RCA), left main (LM), left anterior descending (LAD), and left circumflex (LCX) were localized and imaged using 3- dimensional fat-suppressed FIESTA sequence during end-expiration. The reproducibility of the localization strategy was evaluated by taking the standard of coronary segmentation system recommended by American Heart Association. Results: Eighty-six subjects completed the examination with full respiratory co-operation and the indication ratio was 96.63%. Nine planes were optimized as the standard to target the main branches of coronary arteries, and a comprehensive reproducibility reached 100% in demonstrating the proximal and middle segment of RCA (AHA-18, 19), LM (AHA-1, 2), proximal and middle segment of LAD (AHA-3, 5, 7), and proximal LCX (AHA-10). The reproducibility for the demonstration of distal segments of LAD, LCX, and RCA (AHA-9, 14, 21) was 94.19%, 72.09%, and 96.51%, respectively. Conclusion: This is a simple and practical localization strategy for MRCA. It could image the proximal and middle segments of the coronary arteries with good reproducibility, which indicates the potential for clinical application

  13. Suitable level of suppression in Pinus sylvestris

    Energy Technology Data Exchange (ETDEWEB)

    Hagner, Mats

    1999-10-01

    It is `well known` among Swedish foresters that pine trees need light and cannot grow suppressed. It is also `well known` that old trees that have grown slowly are unable to react with good growth. However, these facts can be questioned in the light of new research as it has been found that thinning reaction is not correlated with age. It is also well known that the commercial value of a pine is closely related to the growth at young age. If the first 20 annual rings close to pith are wide (>3 mm) the log cannot be accepted as first class. This is related to number and size of branches on the young tree and to the features of the juvenile wood. This is to say that a pine must not grow fast when it is small and if this has happened it cannot be cured by artificial debranching or by growing the tree slowly at higher age. Accordingly, young pines should be grown under bigger trees that in their young age were grown under big trees, and so on. Today, when clear cutting is the dominating forest management system, the only way to obtain high quality pine trees is to start the rotation age with stands of very high density. This is of course a very expensive way as dense planting, followed by intensive thinning requires a lot of input. However, if pine is a pioneer species and cannot be grown in multistoried stands, then the economic solution is not present. This was the reason why the annual increment of three pines was measured. They were selected because their different growth pattern showed that old `well known facts` should be revised Working papers 139. 3 refs, 7 figs, 1 tab

  14. Pocket Proteins Suppress Head and Neck Cancer

    Science.gov (United States)

    Shin, Myeong-Kyun; Pitot, Henry C.; Lambert, Paul F.

    2012-01-01

    Head and neck squamous cell carcinomas (HNSCC) is a common cancer in humans long known to be caused by tobacco and alcohol use, but now an increasing percentage of HNSCC is recognized to be caused by the same human papillomaviruses (HPVs) that cause cervical and other anogenital cancers. HPV-positive HNSCCs differ remarkably from HPV-negative HNSCCs in their clinical response and molecular properties. From studies in mice, we know that E7 is the dominant HPV oncoprotein in head and neck cancer. E7 is best known for its ability to inactivate pRb, the product of the retinoblastoma tumor susceptibility gene. However loss of pRb function does not fully account for E7’s potency in causing head and neck cancer. In this study, we characterized the cancer susceptibility of mice deficient in the expression of pRb and either of two related “pocket” proteins, p107 and p130, that are also inactivated by E7. pRb/p107 deficient mice developed head and neck cancer as frequently as do HPV16 E7 transgenic mice. The head and neck epithelia of the pRb/p107 deficient mice also displayed the same acute phenotypes and biomarker readouts as observed in the epithelia of E7 transgenic mice. Mice deficient for pRb and p130 in their head and neck epithelia showed intermediate acute and tumor phenotypes. We conclude that pRb and p107 act together to efficiently suppress head and neck cancer, and are therefore highly relevant targets of HPV16 E7 in its contribution to HPV-positive HNSCC. PMID:22237625

  15. Local Social Networks

    DEFF Research Database (Denmark)

    Sapuppo, Antonio; Sørensen, Lene Tolstrup

    2011-01-01

    Online social networks have become essential for many users in their daily communication. Through a combination of the online social networks with opportunistic networks, a new concept arises: Local Social Networks. The target of local social networks is to promote social networking benefits...... in physical environment in order to leverage personal affinities in the users' surroundings. The purpose of this paper is to present and discuss the concept of local social networks as a new social communication system. Particularly, the preliminary architecture and the prototype of local social networks...

  16. Local Estuary Programs

    Science.gov (United States)

    This page provides information about Local Individual Estuary Programs including links to their NEP homepages, social media, Comprehensive Conservation and Management Plans, and state of the bay reports.

  17. Local Exhaust Ventilation

    DEFF Research Database (Denmark)

    Madsen, Ulla; Breum, N. O.; Nielsen, Peter V.

    Capture efficiency of a local exhaust system, e.g. a kitchen hood, should include only contaminants being direct captured. In this study basic concepts of local exhaust capture efficiency are given, based on the idea of a control box. A validated numerical model is used for estimation of the capt......Capture efficiency of a local exhaust system, e.g. a kitchen hood, should include only contaminants being direct captured. In this study basic concepts of local exhaust capture efficiency are given, based on the idea of a control box. A validated numerical model is used for estimation...

  18. Activation of glucocorticoid receptors in Müller glia is protective to retinal neurons and suppresses microglial reactivity

    OpenAIRE

    Gallina, Donika; Zelinka, Christopher Paul; Cebulla, Colleen; Fischer, Andy J.

    2015-01-01

    Reactive microglia and macrophages are prevalent in damaged retinas. Glucocorticoid signaling is known to suppress inflammation and the reactivity of microglia and macrophages. In the vertebrate retina, the glucocorticoid receptor (GCR) is known to be activated and localized to the nuclei of Müller glia (Gallina et al., 2014). Accordingly, we investigated how signaling through GCR influences the survival of neurons using the chick retina in vivo as a model system. We applied intraocular injec...

  19. Leveraging State And Local Law Enforcement Maritime Homeland Security Practices

    Science.gov (United States)

    2016-03-01

    recreation, national defense, and tourism . To understand the maritime homeland security efforts put into place after 9/11 better, a study of the practices...fire service venturing beyond its fire suppression or emergency medical services role and asserted the value of having firefighters better integrated...national defense, and tourism , so too must be the approach to maritime homeland security. This research examined only the role of state and local law

  20. Cross-cultural differences in emotion suppression in everyday interactions.

    Science.gov (United States)

    Huwaë, Sylvia; Schaafsma, Juliette

    2016-05-11

    Previous research suggests that in collectivistic cultures, people tend to suppress their emotions more than in individualistic cultures. Little research, however, has explored cross-cultural differences in emotion regulation in everyday interactions. Using a daily social interaction method, we examined whether people from collectivistic backgrounds (Chinese exchange students and immigrants from the Moluccas, Indonesia) living in the Netherlands differed from those from individualistic backgrounds (Dutch natives) in emotion suppression during everyday interactions. We also examined whether this depended on their relationship with the interaction partner(s). We found that Chinese participants suppressed positive and negative emotions more than Dutch and Moluccan participants and that this was related to differences in interdependent and independent self-construal across the samples. We also found that Chinese participants suppressed positive emotions less in interactions with close others, whereas Dutch participants suppressed negative emotions more with non-close others. No such differences were found for Moluccans. Our findings support the idea that people from collectivistic cultures suppress emotions more than those from individualistic cultures, but they also suggest that this depends on who the interaction partner is. Furthermore, they suggest that emotion suppression may change when people with collectivistic backgrounds have been raised in individualistic cultures. © 2016 International Union of Psychological Science.