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  1. Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections

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    Hassen Kared

    2018-04-01

    Full Text Available Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV or human immunodeficiency virus (HIV induces the differentiation of natural killer (NK cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions—a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.

  2. Galectin-9 prolongs the survival of septic mice by expanding Tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages.

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    Kadowaki, Takashi; Morishita, Asahiro; Niki, Toshiro; Hara, Junko; Sato, Miwa; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Masaki, Tsutomu; Hattori, Toshio; Matsukawa, Akihiro; Hirashima, Mitsuomi

    2013-12-09

    Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed. We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants. Fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells. Galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. In contrast, such effect was not observed in nude mice, indicating the involvement of T cells in galectin-9-mediated survival prolongation. Galectin-9 decreased TNFα, IL-6, IL-10 and, high mobility group box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9 increased the frequencies of natural killer T (NKT) cells and PDCA-1+ CD11c+ macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8 T cells, γδT cells or conventional DC. As expected, galectin-9 decreased the frequency of Tim-3+ CD4 T cells, most likely Th1 and Th17 cells. Intriguingly, many spleen NK1.1+ NKT cells and pDC-like macrophages expressed Tim-3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1+ NKT cells and pDC-like macrophages. Galectin-9 further increased IL-17+ NK1.1+ NKT cells. These data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages and by modulating the production of early and late proinflammatory cytokines.

  3. Tim-3/galectin-9 regulate the homeostasis of hepatic NKT cells in a murine model of nonalcoholic fatty liver disease.

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    Tang, Zhao-Hui; Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan; Li, Zhiping

    2013-02-15

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti-IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl(2)MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3(+) NKT cells are in an activated state, and Gal-9 directly induces Tim-3(+) NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3-expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9-signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD.

  4. Tim-3/Galectin-9 Regulate the Homeostasis of Hepatic NKT Cells in a Murine Model of Nonalcoholic Fatty Liver Disease

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    Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan

    2013-01-01

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti–IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl2MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3+ NKT cells are in an activated state, and Gal-9 directly induces Tim-3+ NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3–expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9–signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD. PMID:23296703

  5. Tim-3: An activation marker and activation limiter of innate immune cells

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    Gencheng eHan

    2013-12-01

    Full Text Available Tim-3 was initially identified on activated Th1, Th17, and Tc1 cells and induces T cell death or exhaustion after binding to its ligand, Gal-9. The observed relationship between dysregulated Tim-3 expression on T cells and the progression of many clinical diseases has identified this molecule as an important target for intervention in adaptive immunity. Recent data have shown that it also plays critical roles in regulating the activities of macrophages, monocytes, dendritic cells, mast cells, natural killer cells, and endothelial cells. Although the underlying mechanisms remain unclear, dysregulation of Tim-3 expression on these innate immune cells leads to an excessive or inhibited inflammatory response and subsequent autoimmune damage or viral or tumor evasion. In this review, we focus on the expression and function of Tim-3 on innate immune cells and discuss 1 how Tim-3 is expressed and regulated on different innate immune cells; 2 how it affects the activity of different innate immune cells; and 3 how dysregulated Tim-3 expression on innate immune cells affects adaptive immunity and disease progression. Tim-3 is involved in the optimal activation of innate immune cells through its varied expression. A better understanding of the physiopathological role of the Tim-3 pathway in innate immunity will shed new light on the pathogenesis of clinical diseases, such as autoimmune diseases, chronic viral infections, and cancer, and suggest new approaches to intervention.

  6. Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection.

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    Gaia Nebbia

    Full Text Available The S-type lectin galectin-9 binds to the negative regulatory molecule Tim-3 on T cells and induces their apoptotic deletion or functional inactivation. We investigated whether galectin-9/Tim-3 interactions contribute to the deletion and exhaustion of the antiviral T cell response in chronic hepatitis B virus infection (CHB. We found Tim-3 to be expressed on a higher percentage of CD4 and CD8 T cells from patients with CHB than healthy controls (p<0.0001 and to be enriched on activated T cells and those infiltrating the HBV-infected liver. Direct ex vivo examination of virus-specific CD8 T cells binding HLA-A2/peptide multimers revealed that Tim-3 was more highly upregulated on HBV-specific CD8 T cells than CMV-specific CD8 T cells or the global CD8 T cell population in patients with CHB (p<0.001 or than on HBV-specific CD8 after resolution of infection. T cells expressing Tim-3 had an impaired ability to produce IFN-γ and TNF-α upon recognition of HBV-peptides and were susceptible to galectin-9-triggered cell death in vitro. Galectin-9 was detectable at increased concentrations in the sera of patients with active CHB-related liver inflammation (p = 0.02 and was strongly expressed by Kupffer cells within the liver sinusoidal network. Tim-3 blockade resulted in enhanced expansion of HBV-specific CD8 T cells able to produce cytokines and mediate cytotoxicity in vitro. Blocking PD-1 in combination with Tim-3 enhanced the number of patients from whom functional antiviral responses could be recovered and/or the strength of responses, indicating that these co-inhibitory molecules play a non-redundant role in driving T cell exhaustion in CHB. Patients taking antivirals able to potently suppress HBV viraemia continued to express Tim-3 on their T cells and respond to Tim-3 blockade. In summary, both Tim-3 and galectin-9 are increased in CHB and may contribute to the inhibition and deletion of T cells as they infiltrate the HBV-infected liver.

  7. Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD-1, TIGIT, and TIM-3 in Lymphocytes From Patients With Systemic Sclerosis.

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    Fleury, Michelle; Belkina, Anna C; Proctor, Elizabeth A; Zammitti, Christopher; Simms, Robert W; Lauffenburger, Douglas A; Snyder-Cappione, Jennifer E; Lafyatis, Robert; Dooms, Hans

    2018-04-01

    Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc. Co-IR expression levels on subsets of immune cells were analyzed using a 16-color flow cytometry panel. The functional role of co-IRs was determined by measuring cytokine production after in vitro stimulation of SSc and healthy control peripheral blood mononuclear cells (PBMCs) in the presence of co-IR-blocking antibodies. Supernatants from cultures of stimulated PBMCs were added to SSc fibroblasts, and their impact on fibroblast gene expression was measured. Mathematical modeling was used to reveal differences between co-IR functions in SSc patients and healthy controls. Levels of the co-IRs PD-1 and TIGIT were increased, and each was coexpressed, in distinct T cell subsets from SSc patients compared to healthy controls. Levels of TIM-3 were increased in SSc natural killer cells. PD-1, TIGIT, and TIM-3 antibody blockade revealed patient-specific roles of each of these co-IRs in modulating activation-induced T cell cytokine production. In contrast to healthy subjects, blockade of TIGIT and TIM-3, but not PD-1, failed to reverse inhibited cytokine production in SSc patients, indicating that enhanced T cell exhaustion is present in SSc. Finally, cytokines secreted in anti-TIM-3-treated PBMC cultures distinctly changed the gene expression profile in SSc fibroblasts. The altered expression and regulatory capacity of co-IRs in SSc lymphocytes may contribute to disease pathophysiology by modulating the cytokine-mediated cross-talk of

  8. HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications.

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    Lishomwa C Ndhlovu

    2011-04-01

    Full Text Available The T cell immunoglobulin mucin 3 (Tim-3 receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis, we investigated the expression of the Tim-3 receptor on CD8(+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8(+ and CD4(+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8(+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3(+ and Tim-3(- fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.

  9. HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications.

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    Ndhlovu, Lishomwa C; Leal, Fabio E; Hasenkrug, Aaron M; Jha, Aashish R; Carvalho, Karina I; Eccles-James, Ijeoma G; Bruno, Fernanda R; Vieira, Raphaella G S; York, Vanessa A; Chew, Glen M; Jones, R Brad; Tanaka, Yuetsu; Neto, Walter K; Sanabani, Sabri S; Ostrowski, Mario A; Segurado, Aluisio C; Nixon, Douglas F; Kallas, Esper G

    2011-04-26

    The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8(+) T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8(+) and CD4(+) T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8(+) T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3(+) and Tim-3(-) fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.

  10. α-Lactose Improves the Survival of Septic Mice by Blockade of TIM-3 Signaling to Prevent NKT Cell Apoptosis and Attenuate Cytokine Storm.

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    Yao, Yao; Deng, Hai; Li, Pingfei; Zhang, Jian; Zhang, Junbo; Wang, Deping; Li, Songbo; Luo, Yixing; Wei, Zhengping; Bi, Guoyu; Yang, Xiang-Ping; Tang, Zhao-Hui

    2017-03-01

    Sepsis is the leading cause of death among critically ill patients and natural killer T (NKT) cell activation is essential to induce inflammatory cytokine cascade in sepsis. However, little is known about what regulates the NKT cell function during sepsis. Herein, we showed that T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in NKT cells is elevated in experimental mice during sepsis. Tim-3 expression was positively correlated with NKT cell activation and apoptosis. In sepsis, interleukin (IL)-12 secreted by dendritic cell exposure to lipopolysaccharide increased the expression of Tim-3 in NKT cells. Administration of α-lactose to block Tim-3 signaling pathway significantly improved the survival of septic mice, concomitant with reduced IL-12 production by dendritic cells, reduced Tim-3 expression, prevented NKT cell apoptosis, and attenuated production of inflammatory cytokines. Collectively, Tim-3 signaling in NKT cells plays a critical role in the immunopathogenesis of sepsis. Thus, α-lactose could be a promising immunomodulatory agent in the treatment of sepsis.

  11. Increased bovine Tim-3 and its ligand expressions during bovine leukemia virus infection

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    Okagawa Tomohiro

    2012-05-01

    Full Text Available Abstract The immunoinhibitory receptor T cell immunoglobulin domain and mucin domain-3 (Tim-3 and its ligand, galectin-9 (Gal-9, are involved in the immune evasion mechanisms for several pathogens causing chronic infections. However, there is no report concerning the role of Tim-3 in diseases of domestic animals. In this study, cDNA encoding for bovine Tim-3 and Gal-9 were cloned and sequenced, and their expression and role in immune reactivation were analyzed in bovine leukemia virus (BLV-infected cattle. Predicted amino acid sequences of Tim-3 and Gal-9 shared high homologies with human and mouse homologues. Functional domains, including tyrosine kinase phosphorylation motif in the intracellular domain of Tim-3 were highly conserved among cattle and other species. Quantitative real-time PCR analysis showed that bovine Tim-3 mRNA is mainly expressed in T cells such as CD4+ and CD8+ cells, while Gal-9 mRNA is mainly expressed in monocyte and T cells. Tim-3 mRNA expression in CD4+ and CD8+ cells was upregulated during disease progression of BLV infection. Interestingly, expression levels for Tim-3 and Gal-9 correlated positively with viral load in infected cattle. Furthermore, Tim-3 expression level closely correlated with up-regulation of IL-10 in infected cattle. The expression of IFN-γ and IL-2 mRNA was upregulated when PBMC from BLV-infected cattle were cultured with Cos-7 cells expressing Tim-3 to inhibit the Tim-3/Gal-9 pathway. Moreover, combined blockade of the Tim-3/Gal-9 and PD-1/PD-L1 pathways significantly promoted IFN-γ mRNA expression compared with blockade of the PD-1/PD-L1 pathway alone. These results suggest that Tim-3 is involved in the suppression of T cell function during BLV infection.

  12. Statins reduce the expressions of Tim-3 on NK cells and NKT cells in atherosclerosis.

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    Zhang, Na; Zhang, Min; Liu, Ru-Tao; Zhang, Peng; Yang, Chun-Lin; Yue, Long-Tao; Li, Heng; Li, Yong-Kang; Duan, Rui-Sheng

    2018-02-15

    3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have an immuno-regulatory effect in addition to lowing-lipids. Accumulated evidence showed that the expressions of T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) on natural killer (NK) cells increased in atherosclerotic patients and animal models. In this study, 14 patients treated with rosuvastatin and 12 patients with atorvastatin for more than 3 months were included and 20 patients without statins treatment as control. Both statins treatment reduced the expressions of Tim-3 on NK cells and their subtypes, natural killer T (NKT) cells and CD3 + T cells, and increased the proportions of NKT cells among peripheral blood mononuclear cells, accompanied by the decreased levels of total cholesterol, low density lipoprotein, and increased ratios of high density lipoprotein to cholesterol. These may contribute to the functions of statins in the treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with Chlamydia muridarum

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    Peng Bo

    2011-12-01

    Full Text Available Abstract Background Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated. Methods Neutralization antibodies targeting Tim-3 and PD-L1 were used to treat mice. Following an intravaginal infection with C. muridarum organisms, mice with or without the dual antibody treatment were compared for live chlamydial organism shedding from the lower genital tract and inflammatory pathology in the upper genital tract. Results Mice treated with anti-Tim-3 and anti-PD-L1 antibodies displayed a time course of live organism shedding similar to that of mice treated with equivalent amounts of isotype-matched IgG molecules. The combined antibody blocking failed to alter either the lower genital tract cytokine or systemic humoral and cellular adaptive responses to C. muridarum infection. However, the antibody blocking significantly enhanced C. muridarum-induced pathologies in the upper genital tract, including more significant hydrosalpinx and inflammatory infiltration in uterine horn and oviduct tissues. Conclusions The Tim-3 and PD-L1-mediated signaling can significantly reduce pathologies in the upper genital tract without suppressing immunity against chlamydial infection, suggesting that Tim-3 and PD-L1-mediated negative regulation may be manipulated to attenuate tubal pathologies in women persistently infected with C. trachomatis organisms.

  14. Tim-3 Up-regulation in Patients with Gastric Cancer and Peptic Ulcer Disease

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    Naghavi-Alhosseini, Mahdieh; Tehrani, Mohsen; Ajami, Abolghasem; Rafiei, Alireza; Taghvaei, Tarang; Vahedi-Larijani, Laleh; Hossein-Nataj, Hadi; Asgarian-Omran, Hossein

    2017-03-01

    Background: T-cell immunoglobulin and mucin domain protein-3 (Tim-3), an inhibitory immunoregulatory receptor, has been recently implicated in tumor biology and tumor-associated immune suppression. In the present study, expression of Tim-3 was evaluated in gastric cancer (GC) and peptic ulcer disease (PUD) at both mRNA and protein levels. Methods: A total of 133 gastric tissue biopsies, comprising 43 from GC cases, 48 from PUD and 42 from non-ulcer dyspepsia (NUD) serving as controls were collected. Additionally, non-neoplastic adjacent tissue biopsies were also obtained from 6 patients with GC. Infection with Helicobacter pylori was determined by the rapid urease test for all participants and H&E staining was conducted for GC and PUD patients. Tim-3 relative mRNA expression was determined by SYBR Green based Real-Time PCR using β-actin as a reference gene. Tim-3 protein expression was also studied by immunohistochemistry in 7 GC, 7 PUD and 10 NUD tissue samples. Results: Tim-3 was expressed at higher levels in GC (p=0.030) and PUD (p=0.022) cases compared to he NUD group. Among paired samples obtained from gastric cancer patients, tumor tissues showed elevated Tim-3 expression (p=0.019) in comparison with adjacent non-neoplastic biopsies. Tim-3 mRNA findings were supported by detection of more Tim-3 protein in cancerous (p=0.002) and ulcerative (p=0.01) tissues than in controls. Tim-3 was similarly expressed in H. pylori positive and negative cases.Conclusion: Higher Tim-3 expression in patients with gastric cancer and peptic ulcer implies that it might be involved in immune regulation and establishment of these gastrointestinal diseases. Targeted immunotherapy by blocking of inhibitory receptors like Tim-3 could be a promising approach for gastric cancer treatment. Creative Commons Attribution License

  15. Peripheral blood TIM-3 positive NK and CD8+ T cells throughout pregnancy: TIM-3/galectin-9 interaction and its possible role during pregnancy.

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    Matyas Meggyes

    Full Text Available PROBLEM: The T-cell immunoglobulin and mucin domain (TIM family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important negative regulator of Th1 immunity and tolerance induction. Data about the TIM-3/Gal-9 pathway in the pathogenesis of human diseases is emerging, but their possible role during human pregnancy is not precisely known. The aim of our study was to investigate the number, phenotype and functional activity of TIM-3+ peripheral blood mononuclear cells during healthy human pregnancy. METHODS OF STUDY: 57 healthy pregnant women [first trimester (n = 16; second trimester (n = 19; third trimester (n = 22] and 30 non-pregnant controls were enrolled in the study. We measured the surface expression of TIM-3 by cytotoxic T cells, NK cells and NK cell subsets as well as Galectin-9 expression by regulatory T cells by flow cytometry. We analyzed the cytokine production and cytotoxicity of TIM3+ and TIM3- CD8 T and NK cells obtained from non-pregnant and healthy pregnant women at different stages of pregnancy by flow cytometry. Serum Galectin-9 levels were measured by ELISA. RESULTS: Our results show that the numbers of peripheral NK and cytotoxic T cells and their TIM-3 expression do not change between the first, second and third trimesters of pregnancy. Compared to non-pregnant individuals, regulatory T cells show higher level of Galectin-9 expression as pregnancy proceeds, which is in line with the level of Galectin-9 in the patients sera. Cytotoxic T cells, NK cells and NK cell subsets expressing TIM-3 molecule show altered cytokine production and cytotoxicity during pregnancy compared to non-pregnant individuals. CONCLUSION: Our results indicate that Galectin-9 expressing regulatory T cells, TIM-3+ cytotoxic T cells and NK cells could play an important role in the

  16. Peripheral blood TIM-3 positive NK and CD8+ T cells throughout pregnancy

    DEFF Research Database (Denmark)

    Meggyes, Matyas; Miko, Eva; Polgar, Beata

    2014-01-01

    PROBLEM: The T-cell immunoglobulin and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important neg...

  17. Effect of TIM-3 Blockade on the Immunophenotype and Cytokine Profile of Murine Uterine NK Cells.

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    Sudipta Tripathi

    Full Text Available NK cells are the most abundant lymphocyte population in the feto-maternal interface during gestation. The uterine NK cells (uNK are transient, have a unique immunophenotype and produce a number of cytokines. These cytokines play an important role in establishment and maintenance of vascular remodeling and tolerance associated with successful pregnancy. The uNK cells also express TIM-3 during gestation and blockade of TIM-3 expression results in fetal loss in mice. In this study we determined the effect of TIM-3 blockade on uNK cells. Specifically we observed surface receptor phenotype and cytokine production by uNK cells following TIM-3 blockade. Our results show that TIM-3 plays a role in regulating the uNK cells and contributes to the maintenance of tolerance at the feto-maternal interface.

  18. The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells

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    Isabel Gonçalves Silva

    2017-08-01

    Full Text Available Acute myeloid leukemia (AML is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased translation and exocytosis of the immune receptor Tim-3 and its ligand galectin-9. This occurs in a protein kinase C and mTOR (mammalian target of rapamycin-dependent manner. Tim-3 participates in galectin-9 secretion and is also released in a free soluble form. Galectin-9 impairs the anti-cancer activity of cytotoxic lymphoid cells including natural killer (NK cells. Soluble Tim-3 prevents secretion of interleukin-2 (IL-2 required for the activation of cytotoxic lymphoid cells. These results were validated in ex vivo experiments using primary samples from AML patients. This pathway provides reliable targets for both highly specific diagnosis and immune therapy of AML.

  19. Dysregulation of TIM-3-galectin-9 pathway in the cystic fibrosis airways.

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    Vega-Carrascal, Isabel

    2012-02-01

    The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.

  20. Dysregulation of TIM-3-galectin-9 pathway in the cystic fibrosis airways.

    LENUS (Irish Health Repository)

    Vega-Carrascal, Isabel

    2011-03-01

    The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.

  1. High affinity anti-TIM-3 and anti-KIR monoclonal antibodies cloned from healthy human individuals.

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    Stefan Ryser

    Full Text Available We report here the cloning of native high affinity anti-TIM-3 and anti-KIR IgG monoclonal antibodies (mAbs from peripheral blood mononuclear cells (PBMC of healthy human donors. The cells that express these mAbs are rare, present at a frequency of less than one per 105 memory B-cells. Using our proprietary multiplexed screening and cloning technology CellSpot™ we assessed the presence of memory B-cells reactive to foreign and endogenous disease-associated antigens within the same individual. When comparing the frequencies of antigen-specific memory B-cells analyzed in over 20 screening campaigns, we found a strong correlation of the presence of anti-TIM-3 memory B-cells with memory B-cells expressing mAbs against three disease-associated antigens: (i bacterial DNABII proteins that are a marker for Gram negative and Gram positive bacterial infections, (ii hemagglutinin (HA of influenza virus and (iii the extracellular domain of anaplastic lymphoma kinase (ALK. One of the native anti-KIR mAbs has similar characteristics as lirilumab, an anti-KIR mAb derived from immunization of humanized transgenic mice that is in ongoing clinical trials. It is interesting to speculate that these native anti-TIM-3 and anti-KIR antibodies may function as natural regulatory antibodies, analogous to the pharmacological use in cancer treatment of engineered antibodies against the same targets. Further characterization studies are needed to define the mechanisms through which these native antibodies may function in healthy and disease conditions.

  2. Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3).

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    Homayouni, Vida; Ganjalikhani-Hakemi, Mazdak; Rezaei, Abbas; Khanahmad, Hossein; Behdani, Mahdi; Lomedasht, Fatemeh Kazemi

    2016-11-01

    As T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes. We immunized a camel with TIM-3 antigen and then, synthesized a VHH phage: mid library from its B cell's transcriptome using nested PCR. Library selection against TIM-3antigen was performed in three rounds of panning. Using phage-ELISA, the most reactive colonies were selected for sub-cloning in soluble protein expression vectors. The Nanobody was purified and confirmed with a nickel-nitrilotriacetic acid (Ni-NTA) column, SDS-PAGE and Western blotting. A flowcytometric analysis was performed to analyze the binding and biologic activities of theTIM-3 specific nanobody with TIM-3 expressing HL-60 and HEK cell lines. Specific 15kD band representing for nanobody was observed on the gel and confirmed with Western blotting. The nanobody showed significant specific immune-reactivity against TIM-3 with a relatively high binding affinity. The nanobody significantly suppressed the proliferation of TIM-3 expressing HL-60 cell line. Finally, we successfully prepared a functional anti-humanTIM-3 specific nanobody with a high affinity and an anti-proliferative activity on an AML cell line in vitro.

  3. TIM-3 is not essential for development of airway inflammation induced by house dust mite antigens

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    Yoshihisa Hiraishi

    2016-10-01

    Conclusions: Our findings indicate that, in mice, TIM-3 is not essential for development of HDM-induced acute or chronic allergic airway inflammation, although it appears to be involved in reduced lymphocyte recruitment during HDM-induced chronic allergic airway inflammation.

  4. Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3

    Directory of Open Access Journals (Sweden)

    Vida Homayouni

    2016-11-01

    Full Text Available Objective(s: As T-cell immunoglobulin and mucin domain 3 (TIM-3 is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes. Materials and Methods:We immunized a camel with TIM-3 antigen and then, synthesized a VHH phagemid library from its B cell’s transcriptome using nested PCR. Library selection against TIM-3antigen was performed in three rounds of panning. Using phage-ELISA, the most reactive colonies were selected for sub-cloning in soluble protein expression vectors. The Nanobody was purified and confirmed with a nickel-nitrilotriacetic acid (Ni-NTA column, SDS-PAGE and Western blotting. A flowcytometric analysis was performed to analyze the binding and biologic activities of theTIM-3 specific nanobody with TIM-3 expressing HL-60 and HEK cell lines. Results:Specific 15kD band representing for nanobody was observed on the gel and confirmed with Western blotting. The nanobody showed significant specific immune-reactivity against TIM-3 with a relatively high binding affinity. The nanobody significantly suppressed the proliferation of TIM-3 expressing HL-60 cell line. Conclusion: Finally, we successfully prepared a functional anti-humanTIM-3 specific nanobody with a high affinity and an anti-proliferative activity on an AML cell line in vitro.

  5. Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Cai, X.Z. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang (China); Huang, W.Y.; Qiao, Y.; Chen, Y.; Du, S.Y.; Chen, D.; Yu, S. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Liu, N. [Department of Nephrology, First Affiliated Hospital, China Medical University, Shenyang (China); Dou, L.Y. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Jiang, Y. [Central Laboratory, First Affiliated Hospital, China Medical University, Shenyang (China); Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang (China); Department of Dermatology, First Affiliated Hospital, China Medical University, Shenyang (China)

    2014-10-17

    The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (r{sub s}=0.283, P=0.049) and serum albumin (r{sub s}=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; r{sub s}=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE.

  6. Involvement of Galectin-9/TIM-3 pathway in the systemic inflammatory response in early-onset preeclampsia.

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    Eva Miko

    Full Text Available Preeclampsia is a common obstetrical disease affecting 3-5% of pregnancies and representing one of the leading causes of both maternal and fetal mortality. Maternal symptoms occur as an excessive systemic inflammatory reaction in response to the placental factors released by the oxidatively stressed and functional impaired placenta. The T-cell immunoglobulin domain and mucin domain (TIM family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction.The aim of our study was to investigate the expression and function of Galectin-9 and TIM-3 molecules by peripheral blood mononuclear cells and the possible role of Galectin-9/TIM-3 pathway in the immunoregulation of healthy pregnancy and early-onset preeclampsia. We determined TIM-3 and Gal-9 expression and cytotoxicicty of peripheral lymphocytes of early-onset preeclamptic women and healthy pregnant woman using flow cytometry.Investigating peripheral lymphocytes of women with early-onset preeclampsia, our results showed a decreased TIM-3 expression by T cells, cytotoxic T cells, NK cells and CD56(dim NK cells compared to healthy pregnant women. Interestingly, we found a notably increased frequency of Galectin-9 positive cells in each investigated lymphocyte population in the case of early-onset preeclamptic patients. We further demonstrated increased cytotoxic activity by cytotoxic T and CD56(dim NK cells in women with early-onset preeclampsia. Our findings showed that the strongest cellular cytotoxic response of lymphocytes occurred in the TIM-3 positive subpopulations of different lymphocytes subsets in early-onset preeclampsia.These data suggest that Gal-9/TIM-3 pathway could play an important role in the immune regulation during pregnancy and the altered Galectin-9 and TIM-3

  7. Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion.

    Science.gov (United States)

    Avery, Lyndsay; Filderman, Jessica; Szymczak-Workman, Andrea L; Kane, Lawrence P

    2018-02-20

    Tim-3 is highly expressed on a subset of T cells during T cell exhaustion in settings of chronic viral infection and tumors. Using lymphocytic choriomeningitis virus (LCMV) Clone 13, a model for chronic infection, we found that Tim-3 was neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim-3 promoted the development of short-lived effector T cells, at the expense of memory precursor development, after acute LCMV infection. These effects were accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3-deficient mice. Thus, Tim-3 is essential for optimal effector T cell responses, and may also contribute to exhaustion by restricting the development of long-lived memory T cells. Taken together, our results suggest that Tim-3 is actually more similar to costimulatory receptors that are up-regulated after T cell activation than to a dominant inhibitory protein like PD-1. These findings have significant implications for the development of anti-Tim-3 antibodies as therapeutic agents.

  8. Feto-maternal immune regulation by TIM-3/galectin-9 pathway and PD-1 molecule in mice at day 14.5 of pregnancy

    DEFF Research Database (Denmark)

    Meggyes, Matyas; Lajko, Adrienn; Palkovics, Tamas

    2015-01-01

    of the haemochorial placenta. Decidual NK, NKT and γ/δ T cells showed increased PD-1 expression and reduced cytotoxic potential when compared to the periphery. TIM-3 expression by NK cells and γ/δ T cells is similar both in the periphery and in the decidua, notably, their relative TIM-3 expression is increased...... locally which is associated with reduced lytic activity. Decidual NKT cells exhibit a reduced TIM-3 expression with increased relative receptor expression and a slightly increased cytotoxicity when compared to the periphery. DISCUSSION: Our data reveals a particularly complex, tissue and cell type......INTRODUCTION: Immunoregulation implies the activation of negative pathways leading to the modulation of specific immune responses. Co-inhibitory receptors (such as PD-1 and TIM-3) represent possible tools for this purpose. PD-1 and TIM-3 have been demonstrated to be present on immune cells...

  9. Upregulation of Tim-3 on CD4(+) T cells is associated with Th1/Th2 imbalance in patients with allergic asthma.

    Science.gov (United States)

    Tang, Fei; Wang, Fukun; An, Liyun; Wang, Xianling

    2015-01-01

    T cell Ig and mucin domain-containing molecule-3 (Tim-3) is a negative regulator preferentially expressed on Th1 cells. Allergic asthma is a clinical syndrome well characterized by Th1/Th2 imbalance. To investigate the role of Tim-3 in the pathogenesis of asthma and its relationship with Th1/Th2 imbalance, a total of 40 patients with allergic asthma and 40 healthy controls were enrolled. Expression of Tim-3 and Th1/Th2 imbalance as well as the relationship between them was analyzed by flow cytometry and real-time PCR. Peripheral blood mononuclear cells (PBMCs) were cultured in vitro and anti-Tim-3 was used to block Tim-3 signaling; Th1/Th2 cytokines in the culture supernatant were detected by enzyme linked immunosorbent assay (ELISA). CD4(+) T cells and B cells were sorted and co-cultured in vitro, and anti-Tim-3 was used to block Tim-3 signaling; Total IgG/IgE in the culture supernatant was detected by ELISA. The mRNA level of T-bet and IFN-γ were significantly decreased in allergic asthma patients, while GATA-3 and IL-4 were significantly increased. Expression of Tim-3 on CD4(+) T cells was much higher in allergic asthma patients and it was negatively correlated with T-bet/GATA-3 ratio or IFN-γ/IL-4 ratio. Blocking of Tim-3 significantly increased Th1 cytokines (TNF-α and IFN-γ) and decreased Th2 cytokines (IL-4, IL-5, IL-13) in the culture supernatant of PBMCs. Blocking of Tim-3 dramatically reduced the production of IgG and IgE in the co-culture supernatant of CD4(+) T cells and B cells. In conclusion, Tim-3 was up-regulated in allergic asthma patients and related with the Th1/Th2 imbalance. Blocking of Tim-3 may be of therapeutic benefit by enhancing the Th1 cytokines response, down-regulating the Th2 cytokines response, and reducing IgG/IgE production.

  10. Towards the natural gauge mediation

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ran [Center for High-Energy Physics, Peking University,Beijing, 100871 (China); Li, Tianjun [State Key Laboratory of Theoretical Physics andKavli Institute for Theoretical Physics, China (KITPC), Institute of Theoretical Physics,Chinese Academy of Sciences, Beijing 100190 (China); School of Physical Electronics, University of Electronic Science and Technology of China,Chengdu 610054 (China); Wang, Liucheng [Bartol Research Institute, Department of Physics and Astronomy,University of Delaware, Newark, DE 19716 (United States); Zhu, Bin [State Key Laboratory of Theoretical Physics andKavli Institute for Theoretical Physics, China (KITPC), Institute of Theoretical Physics,Chinese Academy of Sciences, Beijing 100190 (China); Institute of Physics Chinese Academy of sciences,Beijing 100190 (China)

    2015-10-23

    The sweet spot supersymmetry (SUSY) solves the μ/B{sub μ} problem in the Minimal Supersymmetric Standard Model (MSSM) with gauge mediated SUSY breaking (GMSB) via the generalized Giudice-Masiero (GM) mechanism where only the μ-term and soft Higgs masses are generated at the unification scale of the Grand Unified Theory (GUT) due to the approximate PQ symmetry. Because all the other SUSY breaking soft terms are generated via the GMSB below the GUT scale, there exists SUSY electroweak (EW) fine-tuning problem to explain the 125 GeV Higgs boson mass due to small trilinear soft term. Thus, to explain the Higgs boson mass, we propose the GMSB with both the generalized GM mechanism and Higgs-messenger interactions. The renormalization group equations are runnings from the GUT scale down to EW scale. So the EW symmetry breaking can be realized easier. We can keep the gauge coupling unification and solution to the flavor problem in the GMSB, as well as solve the μ/B{sub μ}-problem. Moreover, there are only five free parameters in our model. So we can determine the characteristic low energy spectra and explore its distinct phenomenology. The fine-tuning measure can be as low as 100. For some benchmark points, the stop mass can be as low as 1.7 TeV while the glunio mass is around 2.5 TeV. The gravitino dark matter can come from a thermal production with the correct relic density and be consistent with the thermal leptogenesis. Because gluino and stop can be relatively light in our model, how to search for such GMSB at the upcoming run II of the LHC experiment could be very interesting.

  11. Immune checkpoint proteins PD-1 and TIM-3 are both highly expressed in liver tissues and correlate with their gene polymorphisms in patients with HBV-related hepatocellular carcinoma.

    Science.gov (United States)

    Li, Zhu; Li, Na; Li, Fang; Zhou, Zhihua; Sang, Jiao; Chen, Yanping; Han, Qunying; Lv, Yi; Liu, Zhengwen

    2016-12-01

    Immune checkpoint proteins programmed death-1 (PD-1) and T-cell immunoglobulin domain and mucin domain containing molecule-3 (TIM-3) expression and their gene polymorphisms have separately been shown to be associated with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study simultaneously examined PD-1 and TIM-3 expression in liver tissues and PD1 and TIM3 polymorphisms and analyzed their correlations in 171 patients with HBV-related HCC and 34 patients with HBV-related cirrhosis.PD-1 and TIM-3 expression in liver tissues were examined by immunohistochemistry and the genotypes of PD1 rs10204525 and TIM3 rs10053538 polymorphisms were determined using genomic DNA extracted from peripheral blood as template.Both PD-1 and TIM-3 expressions in liver infiltrating lymphocytes of HCC tumor tissues were significantly higher than those in tumor adjacent tissues or cirrhotic tissues. The elevated PD-1 and TIM-3 expressions were significantly associated with higher tumor grades. The levels between PD-1 and TIM-3 expression in tumor tissues and tumor adjacent tissues had a significant positive intercorrelation. The expressions of PD-1 and TIM-3 in tumor tissues, tumor adjacent tissues, and cirrhotic tissues were significantly associated with PD1 and TIM3 polymorphisms, with genotype AA of PD1 rs10204525 and genotypes GT+TT of TIM3 rs10053538 being associated with significantly increased PD-1 and TIM-3 expression, respectively.These findings support the potential to improve the efficiency of immune checkpoint-targeted therapy and reduce resistance to the therapy by blocking both PD-1 and TIM-3 and suggest the potential to apply the genotype determination of PD1 rs10204525 and TIM3 rs10053538 as biomarkers of immune checkpoint-directed therapies.

  12. Blocking Tim-3 or/and PD-1 reverses dysfunction of tumor-infiltrating lymphocytes in HBV-related hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Furong; Zeng, Gucheng; Zhou, Shaotang; He, Xiaoshun; Sun, Nianfeng; Zhu, Xiaofeng; Hu, Anbin

    2018-03-22

    The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC. Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study. Blood samples, paired fresh tumor tissues and adjacent tissues were collected, and isolating peripheral blood mononuclear cells, TILs and adjacent-infiltrating lymphocytes were isolated from these samples. The patients were followed-up to allow survival analysis. Tim-3 or/and PD-1 was up-regulated expressed on CD4 + and CD8 + TILs in HBV-HCC patients and a higher proportion of TILs expressed PD-1 alone. Tim-3 + and PD-1 + TILs greatly decreased secretion of IFN-γ and TNF-α. Expression of Tim-3 and PD-1 on TILs negatively correlated with disease-free survival of HCC patients. Direct blockade of Tim-3 and PD-1 in vitro significantly enhanced TILs proliferation and secretion of IFN-γ and TNF-α. Expression of Tim-3 and/or PD-1 on TILs impairs their function and correlates negatively with disease-free survival in HBV-HCC. Direct blockade of Tim-3 and PD-1 restores anti-tumor effects of TILs, which suggests a potential target for novel immunotherapy in HBV-HCC. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  13. Association of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3 polymorphisms with susceptibility and disease progression of HBV infection.

    Directory of Open Access Journals (Sweden)

    Jingyu Liao

    Full Text Available PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3 plays an important role in regulating T cells in hepatitis B virus (HBV infection and hepatocellular carcinoma (HCC. However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma. METHODS: A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection. RESULTS: Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele "C" of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P = 0.033 and genotype "CC" of rs246871 to be associated with an increased probability of HBV-associated HCC (P = 0.007. In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05 while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05. CONCLUSIONS: Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance.

  14. Naturalness from Runaways in Direct Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Schafer-Nameki, Sakura; /UC, Santa Barbara /King' s Coll. London; Tamarit, Carlos; /UC, Santa Barbara; Torroba, Gonzalo; /SLAC

    2011-02-07

    Postulating that the NMSSM singlet is a meson of a microscopic confining theory opens up new model-building possibilities. Based on this, we construct calculable models of direct mediation that solve the {mu}/B{mu} problem and simultaneously lead to realistic phenomenology. The singlet that couples to the Higgs fields develops a runaway produced by soft interactions, then stabilized by a small superpotential perturbation. The mechanism is first realized in an O'Raifeartaigh model of direct gauge mediation with metastable supersymmetry breaking. Focusing then on the microscopic theory, we argue that super QCD with massless and massive flavors in the free magnetic phase gives rise to this dynamics in the infrared. A deformation of the SQCD superpotential leads to large spontaneous R-symmetry breaking, gaugino masses naturally at the scale of the Higgs mass parameters, and absence of CP violating phases.

  15. Regulatory effect of gamma-chain cytokines on expression of TIM-3 on CD8+ T cells in patients with chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    DONG Jie

    2015-02-01

    Full Text Available ObjectiveTo measure the expression of T-cell immunoglobulin- and mucin domain-3-containing molecule 3 (TIM-3 on CD8+ T cells in peripheral blood mononuclear cells (PBMCs among patients with chronic hepatitis B (CHB and to investigate the effect of common gamma-chain cytokines on the expression of TIM-3 on CD8+ T cells in these patients. MethodsFifteen previously untreated patients with CHB who visited the Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, from January to May, 2014, as well as 8 healthy controls, were included in the study. Blood was collected from these subjects, and PBMCs were isolated from blood by Ficoll density gradient centrifugation. PBMCs were separately stimulated with gamma-chain cytokines, interleukin (IL2, IL-7, IL-15, and IL-21, and anti-CD3/CD28, and the untreated cells were used as a negative control. After four days of culture, PBMCs were stained with monoclonal antibody. Flow cytometry was used to measure the expression of TIM-3 on CD8+ T cells. Comparison of continuous data was made by independent-samples t test. ResultsCompared with the untreated group, the anti-CD3/CD28, IL-2, IL-15, and IL-7 groups had significantly increased expression of TIM-3 on CD8+ T cells (9.629%±9.916%, P=0000 1; 3.817%±2.694%, P = 0.000 6; 5.772%±4.732%, P = 0.005 4; 3.560%±2.045%, P = 0.030 2, while the IL-21 group had nonsignificantly increased expression of TIM-3 on CD8+ T cells (2.503%±2.117%, P = 0.934 1. ConclusionAnti-CD3/CD28 and gamma-chain cytokines IL-2, IL-7, and IL-15 can effectively upregulate the expression of TIM-3 on CD8+ T cells in patients with CHB. It indicates that the inhibition of them can not only reduce the expression of TIM-3, but also may enhance the killing function of CD8+ T cells in patients with CHB.

  16. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Heon, Elise K. [University of Maryland Medical Center, Baltimore, MD 21201 (United States); Wulan, Hasi [Department of Plastic and Reconstructive Surgery, PLA General Hospital, Beijing, 100853 (China); Macdonald, Loch P.; Malek, Adel O.; Braunstein, Glenn H.; Eaves, Connie G.; Schattner, Mark D. [Brown University, Providence, RI 02912 (United States); Allen, Peter M.; Alexander, Michael O.; Hawkins, Cynthia A.; McGovern, Dermot W.; Freeman, Richard L. [University of Wisconsin, Madison, WI 53706 (United States); Amir, Eitan P.; Huse, Jason D. [University of Illinois, Chicago, IL 60607 (United States); Zaltzman, Jeffrey S.; Kauff, Noah P.; Meyers, Paul G. [University of Texas, Austin, TX 78712 (United States); Gleason, Michelle H., E-mail: GleasonM@cblabs.org [University of Texas, Austin, TX 78712 (United States); Overholtzer, Michael G., E-mail: OverholtzerM@cblabs.org [University of Texas, Austin, TX 78712 (United States); Wiseman, Sam S. [Ohio State University, Columbus, OH 43210 (United States); and others

    2015-08-14

    IL-15 has pivotal roles in the control of CD8{sup +} memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors. We found that neither IL-2 nor IL-15 induced intratumoral CD8 T cell proliferation by itself, but after CD3/CD28-stimulation, IL-15 induced significantly higher proliferation than IL-2 during early time points, at day 2, day 3 and day 6. However, the IL-15-induced proliferation leveled off at day 9 and day 12, whereas IL-2 induced lower but progressive proliferation at each time point. Furthermore, IL-15 caused an early and robust increase of IFN-γ in the supernatant of TI cell cultures, which diminished at later time points, while the IL-2-induced IFN-γ production remained constant over time. In addition, the IL-15-costimulated CD8 T cells presented higher frequencies of apoptotic cells. The diminishing IL-15-induced response was possibly due to regulatory and/or exhaustion mechanisms. We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells. Blocking Tim-3 function using anti-Tim-3 antibodies resulted in increased IL-15-induced proliferation and IFN-γ production for a prolonged period of time, whereas adding Tim-3 ligand galectin 9 led to reduced proliferation and IFN-γ production. Our results suggest that IL-15 in combination of Tim-3 blocking antibodies could potentially act as an IL-2 alternative in tumor CD8 T cell expansion in vitro, a crucial step in adoptive T cell therapy. - Highlights: • We explored the effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells of breast cancer. • IL-15

  17. A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation.

    Directory of Open Access Journals (Sweden)

    Bridgette Janine Connell

    Full Text Available Amongst the many strategies aiming at inhibiting HIV-1 infection, blocking viral entry has been recently recognized as a very promising approach. Using diverse in vitro models and a broad range of HIV-1 primary patient isolates, we report here that IND02, a type A procyanidin polyphenol extracted from cinnamon, that features trimeric and pentameric forms displays an anti-HIV-1 activity against CXCR4 and CCR5 viruses with 1-7 μM ED50 for the trimer. Competition experiments, using a surface plasmon resonance-based binding assay, revealed that IND02 inhibited envelope binding to CD4 and heparan sulphate (HS as well as to an antibody (mAb 17b directed against the gp120 co-receptor binding site with an IC50 in the low μM range. IND02 has thus the remarkable property of simultaneously blocking gp120 binding to its major host cell surface counterparts. Additionally, the IND02-trimer impeded up-regulation of the inhibitory receptors Tim-3 and PD-1 on CD4+ and CD8+ cells, thereby demonstrating its beneficial effect by limiting T cell exhaustion. Among naturally derived products significantly inhibiting HIV-1, the IND02-trimer is the first component demonstrating an entry inhibition property through binding to the viral envelope glycoprotein. These data suggest that cinnamon, a widely consumed spice, could represent a novel and promising candidate for a cost-effective, natural entry inhibitor for HIV-1 which can also down-modulate T cell exhaustion markers Tim-3 and PD-1.

  18. Galectin-9 ameliorates clinical severity of MRL/lpr lupus-prone mice by inducing plasma cell apoptosis independently of Tim-3.

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    Masahiro Moritoki

    Full Text Available Galectin-9 ameliorates various murine autoimmune disease models by regulating T cells and macrophages, although it is not known what role it may have in B cells. The present experiment shows that galectin-9 ameliorates a variety of clinical symptoms, such as proteinuria, arthritis, and hematocrit in MRL/lpr lupus-prone mice. As previously reported, galectin-9 reduces the frequency of Th1, Th17, and activated CD8(+ T cells. Although anti-dsDNA antibody was increased in MRL/lpr lupus-prone mice, galectin-9 suppressed anti-dsDNA antibody production, at least partly, by decreasing the number of plasma cells. Galectin-9 seemed to decrease the number of plasma cells by inducing plasma cell apoptosis, and not by suppressing BAFF production. Although about 20% of CD19(-/low CD138(+ plasma cells expressed Tim-3 in MRL/lpr lupus-prone mice, Tim-3 may not be directly involved in the galectin-9-induced apoptosis, because anti-Tim-3 blocking antibody did not block galectin-9-induced apoptosis. This is the first report of plasma cell apoptosis being induced by galectin-9. Collectively, it is likely that galectin-9 attenuates the clinical severity of MRL lupus-prone mice by regulating T cell function and inducing plasma cell apoptosis.

  19. Expression of TIM-3, Human β-defensin-2, and FOXP3 and Correlation with Disease Activity in Pediatric Crohn’s Disease with Infliximab Therapy

    Science.gov (United States)

    Kim, Mi Jin; Lee, Woo Yong; Choe, Yon Ho

    2015-01-01

    Background/Aims This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human β-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) in children with Crohn’s disease (CD) during infliximab therapy. Methods We enrolled 20 CD patients who received infliximab treatment for 1 year. Peripheral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals. Results A significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (pinfliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25+ FOXP3+ was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008). Conclusions Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD. PMID:25071071

  20. Effective Natural Supersymmetry from the Yukawa Deflected Mediations

    Directory of Open Access Journals (Sweden)

    Tai-ran Liang

    2017-01-01

    Full Text Available The natural supersymmetry (SUSY requires light (≤1 TeV stop quarks, light sbottom quark, and gluinos. The first generation of squarks can be effectively larger than several TeV which does not introduce any hierarchy problem in order to escape the constraints from LHC. In this paper we consider a Yukawa deflected mediation to realize the effective natural supersymmetry where the interactions between squarks and messengers are made natural under certain Froggatt-Nielsen U(1X charges. The first generation squarks obtain large and positive contribution from the Yukawa deflected mediation. The corresponding phenomenology and sparticle spectra are discussed in detail.

  1. Natural mediators in the oxidation of polycyclic aromatic hydrocarbons by laccase mediator systems

    Energy Technology Data Exchange (ETDEWEB)

    Johannes, C.; Majcherczyk, A.

    2000-02-01

    The oxidation of polycyclic aromatic compounds was studied in systems consisting of laccase from Trametes versicolor and so-called mediator compounds. The enzymatic oxidation of acenaphthene, acenaphthylene, anthracene, and fluorene was mediated by various laccase substrates (phenols and aromatic amines) or compounds produced and secreted by white rot fungi. The best natural mediators, such as phenol, aniline, 4-hydroxybenzoic acid, and 4-hydroxybenzyl alcohol were as efficient as the previously described synthetic compounds ABTS [2,2{prime}-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)] and 1-hydroxybenzotriazole. The oxidation efficiency increased proportionally with the redox potentials of the phenolic mediators up to a maximum value of 0.9 V and decreased thereafter with redox potentials exceeding this value. Natural compounds such as methionine, cysteine, and reduced glutathione, containing sulfhydryl groups, were also active as mediator compounds.

  2. Athymic nude rat. III natural cell mediated cytotoxicity.

    NARCIS (Netherlands)

    W.H. de Jong; P.A. Steerenberg; P.S. Ursem; A.D.M.E. Osterhaus (Albert); J.G. Vos (Joseph); E.J. Ruitenberg (Joost)

    1980-01-01

    textabstractHomozygous rnu/rnu and heterozygous +/rnu rats were investigated and compared with each other for the existence of natural cell-mediated cytotoxicity. Investigated were total, adherent, and nonadherent cell populations from spleen, peritoneal cavity, and mesenteric lymph node. The

  3. Comparison of dynamic expressions of Tim-3 and PD-1 in the brains between toxoplasmic encephalitis-resistant BALB/c and -susceptible C57BL/6 mice.

    Science.gov (United States)

    Wu, Bin; Fu, Xiaoyin; Huang, Bo; Tong, Xinxin; Zheng, Huanqin; Huang, Shiguang; Lu, Fangli

    2014-04-01

    T cells and IFN-γ are essential for controlling the reactivation of toxoplasmic encephalitis (TE), regardless of whether mice are susceptible or resistant to TE. It has been demonstrated that CD8(+) T cells exhausted in chronic Toxoplasma gondii infection result in TE reactivation in C57BL/6 mice. However, this phenomenon had not been reported in genetically TE-resistant BALB/c mice. To explore the immune mechanism of TE in different backgrounds of mice, the dynamic expressions of Tim-3, programmed cell death 1 (PD-1), and their ligands (galectin-9, PD-L1, PD-L2) in brain tissues were compared between TE-resistant BALB/c and -susceptible C57BL/6 mice infected with Prugniaud (Pru, a type II strain) of T. gondii in this study. Compared with infected BALB/c mice, there were remarkable pathological changes with significantly higher histological scores in the brains of C57BL/6 mice at 14, 35, 50, and 70 days postinfection (p.i., P L1 in the brain of C57BL/6 mice than that in BALB/c mice at all the times p.i. (P L1 expressions may contribute to the different immune responses between TE-resistant BALB/c and -susceptible C57BL/6 mice infected with Pru strain of T. gondii.

  4. Enzyme mediated synthesis of polypyrrole in the presence of chondroitin sulfate and redox mediators of natural origin

    Energy Technology Data Exchange (ETDEWEB)

    Grijalva-Bustamante, G.A. [Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Evans-Villegas, A.G. [Departamento de Ciencias Químico Biológicas, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Castillo-Castro, T. del, E-mail: terecat@polimeros.uson.mx [Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Castillo-Ortega, M.M. [Departamento de Investigación en Polímeros y Materiales, Universidad de Sonora, CP 83000 Hermosillo, Sonora (Mexico); Cruz-Silva, R. [Research Center for Exotic Nanocarbons, Shinshu University, 4-17-1 Wakasato, 380-8553, Nagano (Japan); Huerta, F. [Departamento Ingeniería Textil y Papelera, Universitat Politecnica de Valencia, Plaza Ferrandiz y Carbonell, 1, E-03801 Alcoy (Spain); Morallón, E. [Departamento Química Física e Instituto Universitario de Materiales, Universidad de Alicante, Ap. 99, E-03080 Alicante (Spain)

    2016-06-01

    Polypyrrole (PPy) was synthesized by enzyme mediated oxidation of pyrrole using naturally occurring compounds as redox mediators. The catalytic mechanism is an enzymatic cascade reaction in which hydrogen peroxide is the oxidizer and soybean peroxidase, in the presence of acetosyringone, syringaldehyde or vanillin, acts as a natural catalysts. The effect of the initial reaction composition on the polymerization yield and electrical conductivity of PPy was analyzed. Morphology of the PPy particles was studied by scanning electron microscopy and transmission electron microscopy whereas the chemical structure was studied by X-ray photoelectron and Fourier transformed infrared spectroscopic techniques. The redox mediators increased the polymerization yield without a significant modification of the electronic structure of PPy. The highest conductivity of PPy was reached when chondroitin sulfate was used simultaneously as dopant and template during pyrrole polymerization. Electroactive properties of PPy obtained from natural precursors were successfully used in the amperometric quantification of uric acid concentrations. PPy increases the amperometric sensitivity of carbon nanotube screen-printed electrodes toward uric acid detection. - Highlights: • A new method of pyrrole polymerization using naturally occurring redox mediators and doping agents was studied. • The catalytic efficiency of different redox mediators toward pyrrole oxidation was evaluated. • Two different naturally occurring polymers were studied as bifunctional steric stabilizer/doping agents. • Polypyrrole improves the amperometric response of carbon nanotube screen printed electrodes toward uric acid sensing.

  5. Enzyme mediated synthesis of polypyrrole in the presence of chondroitin sulfate and redox mediators of natural origin

    International Nuclear Information System (INIS)

    Grijalva-Bustamante, G.A.; Evans-Villegas, A.G.; Castillo-Castro, T. del; Castillo-Ortega, M.M.; Cruz-Silva, R.; Huerta, F.; Morallón, E.

    2016-01-01

    Polypyrrole (PPy) was synthesized by enzyme mediated oxidation of pyrrole using naturally occurring compounds as redox mediators. The catalytic mechanism is an enzymatic cascade reaction in which hydrogen peroxide is the oxidizer and soybean peroxidase, in the presence of acetosyringone, syringaldehyde or vanillin, acts as a natural catalysts. The effect of the initial reaction composition on the polymerization yield and electrical conductivity of PPy was analyzed. Morphology of the PPy particles was studied by scanning electron microscopy and transmission electron microscopy whereas the chemical structure was studied by X-ray photoelectron and Fourier transformed infrared spectroscopic techniques. The redox mediators increased the polymerization yield without a significant modification of the electronic structure of PPy. The highest conductivity of PPy was reached when chondroitin sulfate was used simultaneously as dopant and template during pyrrole polymerization. Electroactive properties of PPy obtained from natural precursors were successfully used in the amperometric quantification of uric acid concentrations. PPy increases the amperometric sensitivity of carbon nanotube screen-printed electrodes toward uric acid detection. - Highlights: • A new method of pyrrole polymerization using naturally occurring redox mediators and doping agents was studied. • The catalytic efficiency of different redox mediators toward pyrrole oxidation was evaluated. • Two different naturally occurring polymers were studied as bifunctional steric stabilizer/doping agents. • Polypyrrole improves the amperometric response of carbon nanotube screen printed electrodes toward uric acid sensing.

  6. The Emergent Nature of Strategic Mediation in ESL Teacher Education

    Science.gov (United States)

    Kaur, Kuldip

    2015-01-01

    This article concentrates on a practitioner-driven approach to teacher education aimed at advancing ESL teachers' instructional knowledge about writing. Based on activity-centred interaction between a group of Malaysian English teachers and their teacher educator, the discussion demonstrates (1) the emergent, unplanned nature of strategic…

  7. Relationship between natural and heme-mediated antibody polyreactivity

    Energy Technology Data Exchange (ETDEWEB)

    Hadzhieva, Maya; Vassilev, Tchavdar [Stephan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia 1113 (Bulgaria); Bayry, Jagadeesh; Kaveri, Srinivas; Lacroix-Desmazes, Sébastien [Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, F-75006 Paris (France); INSERM, UMR-S 1138, F-75006 Paris (France); Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, F-75006 Paris (France); Dimitrov, Jordan D., E-mail: jordan.dimitrov@crc.jussieu.fr [Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1138, Centre de Recherche des Cordeliers, F-75006 Paris (France); INSERM, UMR-S 1138, F-75006 Paris (France); Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1138, F-75006 Paris (France)

    2016-03-25

    Polyreactive antibodies represent a considerable fraction of the immune repertoires. Some antibodies acquire polyreactivity post-translationally after interaction with various redox-active substances, including heme. Recently we have demonstrated that heme binding to a naturally polyreactive antibody (SPE7) results in a considerable broadening of the repertoire of recognized antigens. A question remains whether the presence of certain level of natural polyreactivity of antibodies is a prerequisite for heme-induced further extension of antigen binding potential. Here we used a second monoclonal antibody (Hg32) with unknown specificity and absence of intrinsic polyreactivity as a model to study the potential of heme to induce polyreactivity of antibodies. We demonstrated that exposure to heme greatly extends the antigen binding potential of Hg32, suggesting that the intrinsic binding promiscuity is not a prerequisite for the induction of polyreactivity by heme. In addition we compared the kinetics and thermodynamics of the interaction of heme-exposed antibodies with a panel of unrelated antigens. These analyses revealed that the two heme-sensitive antibodies adopt different mechanisms of binding to the same set of antigens. This study contributes to understanding the phenomenon of induced antibody polyreactivity. The data may also be of importance for understanding of physiological and pathological roles of polyreactive antibodies. - Highlights: • Exposure of certain monoclonal IgE antibodies to heme results in gain of antigen binding polyreactivity. • Natural polyreactivity of antibodies is dispensable for acquisition of polyreactivity through interaction with heme. • Heme-induced monoclonal IgE antibodies differ in their thermodynamic mechanisms of antigen recognition.

  8. «Natural» intercultural mediation: reflections from an experience in Orriols (Valencia

    Directory of Open Access Journals (Sweden)

    Marcela Jabbaz

    2013-12-01

    Full Text Available This text provides a reflection on the intercultural «natural » mediation, its differentiation with respect to the professional mediation and its limitations within social exclusion politics. The authors base their arguments in information collected from a research performed in Valencia, with European funding and under the responsibility of three NGO that collaborated very actively in the fieldwork. The reflections are centered in the case of the Valencian neighborhood of Orriols. A first section describes the neighborhood. Later, different speeches of foreign and indigenous neighbors are undertaken and the relations among both are characterized. Finally, the authors define the «natural» intercultural mediation, with special attention to its fortresses and weaknesses. The authors emphasize that the potentialities of the mediation can be developed with a correct articulation between Administration and Civil Society and in combination with social politics of prevention and eradication of social exclusion

  9. Inhibition of natural killer cell-mediated cytotoxicity by lipids extracted from Mycobacterium bovis BCG

    NARCIS (Netherlands)

    Roozemond, R. C.; Halperin, M.; Das, P. K.

    1985-01-01

    Several studies have demonstrated an augmentation of natural killer (NK) cell-mediated cytotoxicity by various adjuvants including BCG. Inhibitory effects of BCG have also been reported, particularly for relatively high doses. Because the cell wall of Mycobacterium bovis BCG contains a high

  10. Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

    Science.gov (United States)

    Zha, Weibin

    2018-04-01

    The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

  11. TeV Scale Mirage Mediation and Natural Little SUSY Hierarchy

    OpenAIRE

    Choi, Kiwoon; Jeong, Kwang Sik; Kobayashi, Tatsuo; Okumura, Ken-ichi

    2006-01-01

    TeV scale mirage mediation has been proposed as a supersymmetry breaking scheme reducing the fine tuning for electroweak symmetry breaking in the minimal supersymmetric extension of the standard model. We discuss a moduli stabilization set-up for TeV scale mirage mediation which allows an extra-dimensional interpretation for the origin of supersymmetry breaking and naturally gives an weak-scale size of the Higgs B-parameter. The set-up utilizes the holomorphic gauge kinetic functions dependin...

  12. TeV scale mirage mediation and natural little supersymmetric hierarchy

    International Nuclear Information System (INIS)

    Choi, Kiwoon; Jeong, Kwang Sik; Kobayashi, Tatsuo; Okumura, Ken-ichi

    2007-01-01

    TeV scale mirage mediation has been proposed as a supersymmetry-breaking scheme reducing the fine-tuning for electroweak symmetry breaking in the minimal supersymmetric extension of the standard model. We discuss a moduli stabilization setup for TeV scale mirage mediation which allows an extradimensional interpretation for the origin of supersymmetry breaking and naturally gives a weak-scale size of the Higgs B parameter. The setup utilizes the holomorphic gauge kinetic functions depending on both the heavy dilaton and the light volume modulus whose axion partners are assumed to be periodic fields. We also examine the low-energy phenomenology of TeV scale mirage mediation, particularly the constraints from electroweak symmetry breaking and flavor changing neutral current processes

  13. Trauma or growth after a natural disaster? The mediating role of rumination processes

    Directory of Open Access Journals (Sweden)

    Felipe E. García

    2015-07-01

    Full Text Available The aim of this study was to test a cognitive model of posttraumatic symptoms (PTS and posttraumatic growth (PTG after exposure to a natural disaster. It was hypothesized that although subjective severity of trauma would be related to the severity of PTS, this relation would be mediated by brooding and cognitive strategies related to the presence of repetitive negative content in thoughts. Furthermore, the relation between severity and PTG would be fully mediated by deliberate rumination (DR, cognitive strategies related to conscious efforts focused on handling the event. To evaluate the cognitive model, adults (N=351 who lost their homes as a result of the earthquake and tsunami that occurred in Chile on February 27, 2010, were selected. Structural equation modeling was used to analyze the data. The resulting model had adequate indices of goodness adjustment and showed that brooding completely mediated the relation between subjective severity and PTS, and DR completely mediated the relation between subjective severity, brooding, and PTG. These results highlight the role of both the content and process of rumination in mediating the association between subjective severity of trauma, PTS, and PTG. The implications of these results for a more comprehensive model of symptom severity that occurs after trauma are discussed.

  14. Natural killer cell-mediated cytotoxicity is increased by a type II arabinogalactan from Anoectochilus formosanus.

    Science.gov (United States)

    Yang, Li-Chan; Lai, Ching-Yi; Lin, Wen-Chuan

    2017-01-02

    This study investigated the effects of a type II arabinogalactan from Anoectochilus formosanus (AGAF) on natural killer (NK) cell-mediated cytotoxicity and the possible underlying mechanisms. This study reported that sustained exposure to AGAF increased NK-92MI cell-mediated cytotoxicity in a time- and concentration-dependent manner, as characterized according to the cellular lactic dehydrogenase leakage from K562 leukemia cells. Additionally, antibody neutralization studies have reported that interferon (IFN)-γ, but not perforin or tumor necrosis factor-α, released by NK-92MI NK cells is crucial in enhancing cytotoxicity through an autocrine loop. In this study, AGAF was further demonstrated to induce IFN-γ expression, increasing the susceptibility to NK-92MI cell-mediated cytotoxicity through the toll-like receptor (TLR)-2, TLR4, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB pathways. A pharmacological study revealed that Janus kinase 2/signal transducers and activators of the signal transducers and of transcription 3 signaling are involved in IFN-γ-induced NK cell-mediated cytotoxicity. Copyright © 2016. Published by Elsevier Ltd.

  15. Comparative study of the efficiency of synthetic and natural mediators in laccase-assisted bleaching of eucalyptus kraft pulp.

    Science.gov (United States)

    Moldes, D; Díaz, M; Tzanov, T; Vidal, T

    2008-11-01

    The natural phenolic compounds syringaldehyde and vanillin were compared to the synthetic mediators 1-hydroxybenzotriazole, violuric acid and promazine in terms of boosting efficiency in a laccase-assisted biobleaching of eucalyptus kraft pulp. Violuric acid and 1-hydroxybenzotriazole revealed to be the most effective mediators of the bioprocess. Nevertheless, laccase-syringaldehyde system also improved the final pulp properties (28% delignification and 63.5% ISO brightness) compared to the process without mediator (23% and 61.5% respectively), in addition to insignificant denaturation effect over laccase. The efficiency of the biobleaching process was further related to changes in non-conventionally used optical and chromatic parameters of pulp, such as (L*), chroma (C*) and dye removal index (DRI) showing good correlation. Adverse coupling reactions of the natural phenolic mediators on pulp lignin were predicted by electrochemical studies, demonstrating the complexity of the laccase-mediator reaction on pulp.

  16. Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production

    Directory of Open Access Journals (Sweden)

    József Tőzsér

    2016-01-01

    Full Text Available IL-1β is one of the main proinflammatory cytokines that regulates a broad range of immune responses and also participates in several physiological processes. The canonical production of IL-1β requires multiprotein complexes called inflammasomes. One of the most intensively studied inflammasome complexes is the NLRP3 inflammasome. Its activation requires two signals: one signal “primes” the cells and induces the expression of NLRP3 and pro-IL-1β, while the other signal leads to the assembly and activation of the complex. Several stimuli were reported to function as the second signal including reactive oxygen species, lysosomal rupture, or cytosolic ion perturbation. Despite very intensive studies, the precise function and regulation of the NLRP3 inflammasome are still not clear. However, many chronic inflammatory diseases are related to the overproduction of IL-1β that is mediated via the NLRP3 inflammasome. In this review, we aimed to provide an overview of studies that demonstrated the effect of plant-derived natural compounds on NLRP3 inflammasome-mediated IL-1β production. Although many of these studies lack the mechanistic explanation of their action, these compounds may be considered as complementary supplements in the treatment of chronic inflammatory diseases, consumed as preventive agents, and may also be considered as molecular tools to study NLRP3 function.

  17. Natural Gravitino Dark Matter and Thermal Leptogenesis in Gauge-Mediated Supersymmetry-Breaking Models

    CERN Document Server

    Fujii, M; Fujii, Masaaki

    2002-01-01

    We point out that there is no cosmological gravitino problem in a certain class of gauge-mediated supersymmetry-breaking (GMSB) models. The constant term in the superpotential naturally causes small mixings between the standard-model and messenger fields, which give rise to late-time decays of the lightest messenger fields. This decay provides an exquisite amount of entropy, which dilutes the thermal relics of the gravitinos down to just the observed mass density of the dark matter. This remarkable phenomenon takes place automatically, irrespective of the gravitino mass and the reheating temperature of inflation, once the gravitinos and messenger fields are thermalized in the early Universe. In this class of GMSB models, there is no strict upper bound on the reheating temperature of inflation, which makes the standard thermal leptogenesis the most attractive candidate for the origin of the observed baryon asymmetry in the present Universe.

  18. Cigarette Smoke-mediated Perturbations of the Immune Response: A New Therapeutic Approach with Natural Compounds.

    Science.gov (United States)

    Magrone, Thea; Russo, Matteo Antonio; Jirillo, Emilio

    2016-01-01

    Cigarette smoke (CS) accounts for the outcome of several pathologies, even including lung cancer, cardiovascular disease and chronic obstructive pulmonary disease (COPD). Under healthy conditions, lung immune system becomes tolerant in response to various external stimuli. CS exposure alters the pulmonary immune equilibrium, thus leading to a condition of hyper activation of the local innate and adaptive immunity. COPD is one of the major complications of chronic CS exposure where a pro-inflammatory profile of the pulmonary and systemic immunity is predominant. In this review, alternative treatments with natural products to mitigate CS-mediated pulmonary inflammation are proposed. In particular, polyphenols, a class of natural compounds largely present in fruits and vegetables, have been shown to act as anti-inflammatory agents. Accordingly, recent experimental and clinical evidences support polyphenol-mediated potential health benefits in smokers. For instance, pomegranate juice is able to attenuate the damage provoked by CS on cultured human alveolar macrophages. In addition, maqui beery extract has been proven to normalize H2O2 and interleukin-6 levels in exhaled breath condensate in healthy smokers. However, some limitations of alternative treatments are represented by a better knowledge of the mechanism(s) of action exerted by polyphenols and by the lack of animal models of COPD. In any case, the potential targets of polyphenols in the course of COPD will be outlined with special reference to the activation of T regulatory cells as well as to the inhibition of the polymorphonuclear cell and monocyte respiratory burst and of the NF-κB pathway, respectively. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Synthesis of naturally-derived macromolecules through simplified electrochemically mediated ATRP

    Directory of Open Access Journals (Sweden)

    Paweł Chmielarz

    2017-11-01

    Full Text Available The flavonoid-based macroinitiator was received for the first time by the transesterification reaction of quercetin with 2-bromoisobutyryl bromide. In accordance with the “grafting from” strategy, a naturally-occurring star-like polymer with a polar 3,3',4',5,6-pentahydroxyflavone core and hydrophobic poly(tert-butyl acrylate (PtBA side arms was synthesized via a simplified electrochemically mediated ATRP (seATRP, utilizing only 78 ppm by weight (wt of a catalytic CuII complex. To demonstrate the possibility of temporal control, seATRP was carried out utilizing a multiple-step potential electrolysis. The rate of the polymerizations was well-controlled by applying optimal potential values during preparative electrolysis to prevent the possibility of intermolecular coupling of the growing polymer arms. This appears to be the first report using on-demand seATRP for the synthesis of QC-(PtBA-Br5 pseudo-star polymers. The naturally-derived macromolecules showed narrow MWDs (Đ = 1.08–1.11. 1H NMR spectral results confirm the formation of quercetin-based polymers. These new flavonoid-based polymer materials may find applications as antifouling coatings and drug delivery systems.

  20. BaCO3 mediated modifications in structural and magnetic properties of natural nanoferrites

    Science.gov (United States)

    Widanarto, W.; Jandra, M.; Ghoshal, S. K.; Effendi, M.; Cahyanto, W. T.

    2015-04-01

    Preparing M-type barium hexaferrite and improving the magnetic response of natural ferrites by incorporating barium carbonate (BaCO3) is ever-demanding. Series of barium carbonate doped ferrites with composition (100-x)Fe3O4·xBaCO3 (x=0, 10, 20, 30 wt%) are prepared through solid state reaction method and sintered gradually at temperatures of 800 and 1000 °C. Nanoparticles of natural ferrite and commercial BaCO3 are used as raw materials. Impacts of BaCO3 on structural and magnetic properties of these synthesized ferrites are inspected. The obtained ferrites are characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) at room temperature. Uniform barium hexaferrite particles in terms of both morphology and size are not achieved. The average crystallite size of BaFe12O19 is observed to be within 30-600 nm. The sintering process results phase transformation from Fe3O4 (magnetite) to α-Fe2O3 (hematite) and the formation of hexagonal barium ferrite crystals. The occurrence of barium crystal is found to enhance with the increase of BaCO3 concentrations up to 20 wt% and suddenly drop at 30 wt%. Saturation and remanent magnetization of the doped ferrites are significantly augmented up to 16.37 and 8.92 emu g-1, respectively compared to their pure counterpart. Furthermore, the coercivity field is slightly decreased as BaCO3 concentrations are increased. BaCO3 mediated improvements in the magnetic response of natural ferrites are demonstrated.

  1. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction....... From the perspective of mediatization research, the most important effect of the media stems from their embeddedness in culture and society....

  2. Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of local PD-1+ TIM-3+ CD8+ exhausted T cells.

    Science.gov (United States)

    Khan, Arif A; Srivastava, Ruchi; Chentoufi, Aziz A; Geertsema, Roger; Thai, Nhi Thi Uyen; Dasgupta, Gargi; Osorio, Nelson; Kalantari, Mina; Nesburn, Anthony B; Wechsler, Steven L; BenMohamed, Lbachir

    2015-07-01

    Most blinding ocular herpetic disease is due to reactivation of herpes simplex virus 1 (HSV-1) from latency rather than to primary acute infection. No herpes simplex vaccine is currently available for use in humans. In this study, we used the HLA-A*02:01 transgenic (HLA Tg) rabbit model of ocular herpes to assess the efficacy of a therapeutic vaccine based on HSV-1 gD epitopes that are recognized mainly by CD8(+) T cells from "naturally" protected HLA-A*02:01-positive, HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease). Three ASYMP CD8(+) T-cell epitopes (gD(53-61), gD(70-78), and gD(278-286)) were linked with a promiscuous CD4(+) T-cell epitope (gD(287-317)) to create 3 separate pairs of CD4-CD8 peptides, which were then each covalently coupled to an Nε-palmitoyl-lysine moiety, a Toll-like receptor 2 (TLR-2) ligand. This resulted in the construction of 3 CD4-CD8 lipopeptide vaccines. Latently infected HLA Tg rabbits were immunized with a mixture of these 3 ASYMP lipopeptide vaccines, delivered as eye drops in sterile phosphate-buffered saline (PBS). The ASYMP therapeutic vaccination (i) induced HSV-specific CD8(+) T cells that prevent HSV-1 reactivation ex vivo from latently infected explanted trigeminal ganglia (TG), (ii) significantly reduced HSV-1 shedding detected in tears, (iii) boosted the number and function of HSV-1 gD epitope-specific CD8(+) T cells in draining lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+) TIM-3+ CD8(+) T cells. The results underscore the potential of an ASYMP CD8(+) T-cell epitope-based therapeutic vaccine strategy against recurrent ocular herpes. Seventy percent to 90% of adults harbor herpes simplex virus 1 (HSV-1), which establishes lifelong latency in sensory neurons of the trigeminal ganglia. This latent state sporadically switches to spontaneous reactivation, resulting in viral shedding in tears. Most blinding

  3. Self-esteem mediates the relationship between connectedness to nature and body appreciation in women, but not men.

    Science.gov (United States)

    Swami, Viren; von Nordheim, Laura; Barron, David

    2016-03-01

    Connectedness to nature (i.e., an affective and experiential connection to nature) is known to have a positive effect on psychological well-being, but its specific associations with body image have not been fully examined. To attend to this oversight, we conducted a preliminary investigation of associations between connectedness to nature and body appreciation. A total of 380 British adults completed measures of connectedness to nature, body appreciation, and self-esteem. Bivariate correlations revealed significant positive associations between all variables in women. In men, body appreciation was significantly correlated with self-esteem, but not connectedness to nature. Mediation analysis showed that, in women, self-esteem fully mediated the relationship between connectedness to nature and body appreciation. In men, body appreciation was significantly associated with self-esteem, but not connectedness to nature. These results point to a potential route for improving body image among women through connectedness to nature and self-esteem, but further research is necessary. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Mixed Signals: Co-Stimulation in Invariant Natural Killer T Cell-Mediated Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Susannah C. Shissler

    2017-11-01

    Full Text Available Invariant natural killer T (iNKT cells are an integral component of the immune system and play an important role in antitumor immunity. Upon activation, iNKT cells can directly kill malignant cells as well as rapidly produce cytokines that stimulate other immune cells, making them a front line defense against tumorigenesis. Unfortunately, iNKT cell number and activity are reduced in multiple cancer types. This anergy is often associated with upregulation of co-inhibitory markers such as programmed death-1. Similar to conventional T cells, iNKT cells are influenced by the conditions of their activation. Conventional T cells receive signals through the following three types of receptors: (1 T cell receptor (TCR, (2 co-stimulation molecules, and (3 cytokine receptors. Unlike conventional T cells, which recognize peptide antigen presented by MHC class I or II, the TCRs of iNKT cells recognize lipid antigen in the context of the antigen presentation molecule CD1d (Signal 1. Co-stimulatory molecules can positively and negatively influence iNKT cell activation and function and skew the immune response (Signal 2. This study will review the background of iNKT cells and their co-stimulatory requirements for general function and in antitumor immunity. We will explore the impact of monoclonal antibody administration for both blocking inhibitory pathways and engaging stimulatory pathways on iNKT cell-mediated antitumor immunity. This review will highlight the incorporation of co-stimulatory molecules in antitumor dendritic cell vaccine strategies. The use of co-stimulatory intracellular signaling domains in chimeric antigen receptor-iNKT therapy will be assessed. Finally, we will explore the influence of innate-like receptors and modification of immunosuppressive cytokines (Signal 3 on cancer immunotherapy.

  5. Corrosion inhibition of iota-carrageenan natural polymer on aluminum in presence of zwitterion mediator in HCl media

    International Nuclear Information System (INIS)

    Fares, Mohammad M.; Maayta, A.K.; Al-Mustafa, Jamil A.

    2012-01-01

    Highlights: ► Inhibition of Al by ι-carrageenan in the presence of zwitterion mediator was investigated. ► Considerable improvement in inhibition efficiency observed in the presence of zwitterion mediator. ► Coherent physical adsorption layer was evidenced by kinetic and thermodynamic parameters. ► Small but consistent fractured island layers observed after acid exposure as revealed by SEM images. - Abstract: ι-Carrageenan a natural polymer has been used as corrosion inhibitor of aluminum in presence of pefloxacin mesylate, acting as zwitterionic mediator, in acidic medium. Considerable improvement in inhibition efficiency occurred in the presence of the mediator. Activation energy of corrosion and other thermodynamic parameters such as standard free energy, standard enthalpy, and standard entropy of the adsorption process revealed better and well-ordered physical adsorption layers in presence of pefloxacin. Adsorption isotherms in absence or presence of pefloxacin mediator appropriately fit in the Langmuir isotherms. The scanning electron microscope (SEM) images demonstrated smooth, glossy, and relatively coherent adsorption layers of the inhibitor on the metal surface in aqueous solution. After the exposure to 2.0 M HCl for 2 h, a smaller but consistent regular shaped fractured layer is obtained.

  6. Predator-mediated natural selection on the wings of the damselfly Calopteryx splendens: differences in selection among trait types.

    Science.gov (United States)

    Kuchta, Shawn R; Svensson, Erik I

    2014-07-01

    Traits that increase mating success in males may come at a cost, such as an increased risk of predation. However, predator-mediated selection is challenging to document in natural populations, hampering our understanding of the trade-offs between sexual selection and predation. Here we report on a study of predator-mediated natural selection on wing traits in the damselfly Calopteryx splendens, the males of which possess conspicuous wing patches. Wagtails (genus Motacilla) are important avian predators of C. splendens, capturing them in flight and removing the wings prior to consumption. Using geometric morphometric techniques, we quantified the strength and mode of selection on wing traits by comparing wings from depredated individuals with the standing variation present in the population. Our results reveal that predator-mediated selection is stronger on secondary sexual characters than on size and shape, suggesting that traits related to flight performance are closer to their adaptive peaks. This could be a consequence of the long-term evolutionary association with avian predators, whereas stronger selection on conspicuous secondary sexual traits may reflect trade-offs between sexual and natural selection. Finally, even though C. splendens possesses nearly identical fore- and hindwings, we found evidence for divergent selection between them.

  7. Role of NKG2D, DNAM-1 and natural cytotoxicity receptors in cytotoxicity toward rhabdomyosarcoma cell lines mediated by resting and IL-15-activated human natural killer cells.

    Science.gov (United States)

    Boerman, Gerharda H; van Ostaijen-ten Dam, Monique M; Kraal, Kathelijne C J M; Santos, Susy J; Ball, Lynne M; Lankester, Arjan C; Schilham, Marco W; Egeler, R Maarten; van Tol, Maarten J D

    2015-05-01

    Children with advanced stages (relapsed/refractory and stage IV) of rhabdomyosarcoma (RMS) have a poor prognosis despite intensive chemotherapy and autologous stem cell rescue, with 5-year survival rates ranging from 5 to 35 %. Development of new, additional treatment modalities is necessary to improve the survival rate. In this preclinical study, we investigated the potential of resting and cytokine-activated natural killer (NK) cells to lyse RMS cell lines, as well as the pathways involved, to explore the eventual clinical application of (activated) NK cell immunotherapy. RMS cell lines (n = 3 derived from embryonal RMS and n = 2 derived from alveolar RMS) were susceptible to cytolysis mediated by resting NK cells, and this susceptibility was significantly increased using IL-15-activated NK cells. Flow cytometry and cytolytic assays were used to define the activating and inhibitory pathways of NK cells involved in recognizing and lysing RMS cells. NKG2D and DNAM-1 receptor-ligand interactions were essential in cytolysis by resting NK cells, as simultaneous blocking of both pathways resulted in almost complete abrogation of the cytotoxicity. In contrast, combined blocking of DNAM-1 and NKG2D only led to partial reduction of the lytic activity of IL-15-activated NK cells. In this respect, residual lysis was, at least partly, mediated by pathways involving the natural cytotoxicity receptors NKp30 and NKp46. These findings support further exploration of NK cell-based immunotherapy as adjuvant modality in current treatment strategies of RMS.

  8. Spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis C virus-infected chimpanzees.

    Science.gov (United States)

    Verstrepen, B E; Nieuwenhuis, I G; Mooij, P; Bogers, W M; Boonstra, A; Koopman, G

    2016-07-01

    In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees. © 2016 British Society for Immunology.

  9. Plant Species Diversity Mediates Ecosystem Stability of Natural Dune Grasslands in Response to Drought

    NARCIS (Netherlands)

    Rooijen, van Nils M.; Keersmaecker, de Wanda; Ozinga, Wim A.; Coppin, Pol; Hennekens, Stephan M.; Schaminée, Joop H.J.; Somers, Ben; Honnay, Olivier

    2015-01-01

    How plant species diversity can mediate the temporal stability of ecosystem functioning during periods of environmental stress is still a pressing question in ecology, certainly in the context of predicted increasing frequencies and intensities of climate extremes, such as drought. The vast

  10. Longitudinal Test of Self-Determination Theory's Motivation Mediation Model in a Naturally Occurring Classroom Context

    Science.gov (United States)

    Jang, Hyungshim; Kim, Eun Joo; Reeve, Johnmarshall

    2012-01-01

    This study provides the first longitudinally designed, classroom-based empirical test of self-determination theory's motivation mediation model. Measures of perceived autonomy support, motivation (autonomy need satisfaction), engagement, and achievement were collected from 500 (257 females, 243 males) 8th-grade students in Korea in a 3-wave…

  11. The relationship between natural outdoor environments and cognitive functioning and its mediators

    NARCIS (Netherlands)

    Zijlema, Wilma L.; Triguero-Mas, Margarita; Smith, Graham; Cirach, Marta; Martinez, David; Dadvand, Payam; Gascon, Mireia; Jones, Marc; Gidlow, Christopher; Hurst, Gemma; Masterson, Daniel; Ellis, Naomi; van den Berg, Magdalena; Maas, Jolanda; van Kamp, Irene; van den Hazel, Peter; Kruize, Hanneke; Nieuwenhuijsen, Mark J.; Julvez, Jordi

    2017-01-01

    Background Urban residents may experience cognitive fatigue and little opportunity for mental restoration due to a lack of access to nature. Natural outdoor environments (NOE) are thought to be beneficial for cognitive functioning, but underlying mechanisms are not clear. Objectives To investigate

  12. Ribosome-mediated synthesis of natural product-like peptides via cell-free translation.

    Science.gov (United States)

    Maini, Rumit; Umemoto, Shiori; Suga, Hiroaki

    2016-10-01

    Peptide natural products (PNPs) represent a unique class of compounds known for their fascinating structural motifs with important biological activities. Lately, PNPs have garnered a lot of interest for their application in drug discovery. Nevertheless, lack of diversity oriented synthetic/biosynthetic platforms to generate large natural product-like libraries has limited their development as peptide therapeutics. The promiscuity of cell-free translation has allowed for the synthesis of artificial PNPs having complex structural features. Modified cell-free translation systems coupled with the display technologies have generated diverse natural product-like peptide libraries and led to the discovery of several biologically active molecules. Such technologies have drastically decreased the time to obtain peptide drug leads and therefore, revolutionized the field of peptide drug discovery. In this account, we review recent developments in the synthesis of natural product-like peptides via cell-free translation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Learning as conceptual change: Factors mediating the development of preservice elementary teachers' views of nature of science

    Science.gov (United States)

    Abd-El-Khalick, Fouad; Akerson, Valarie L.

    2004-09-01

    This study assessed, and identified factors in participants' learning ecologies that mediated, the effectiveness of an explicit reflective instructional approach that satisfied conditions for learning as conceptual change on preservice elementary teachers' views of nature of science (NOS). Participants were 28 undergraduate students enrolled in an elementary science methods course. A purposively selected focus group of six participants who showed differential growth in terms of their NOS views were closely followed throughout the study. The Views of Nature of Science Questionnaire-Form B (VNOS-B) in conjunction with individual interviews was used to assess participants' views prior to and at the conclusion of the study. Other data sources included weekly reflection papers, exit interviews, and an instructor's log. Initially, the greater majority of participants held naïve views of NOS. Substantial and favorable changes in these views were evident as a result of the intervention. An examination of the development of the focus group participants' NOS views indicated that the effectiveness of the intervention was mediated by motivational, cognitive, and worldview factors. These were related to internalizing the importance and utility of teaching and learning about NOS, exhibiting a deep processing approach to learning, and viewing science and religion as two distinct rather than opposing enterprises.

  14. Face, Body, and Center of Gravity Mediate Person Detection in Natural Scenes

    Science.gov (United States)

    Bindemann, Markus; Scheepers, Christoph; Ferguson, Heather J.; Burton, A. Mike

    2010-01-01

    Person detection is an important prerequisite of social interaction, but is not well understood. Following suggestions that people in the visual field can capture a viewer's attention, this study examines the role of the face and the body for person detection in natural scenes. We observed that viewers tend first to look at the center of a scene,…

  15. Earthworm symbiont Verminephrobacter eiseniae mediates natural transformation within the host egg capsules using type IV pili

    Directory of Open Access Journals (Sweden)

    SEANA Kelyn DAVIDSON

    2014-10-01

    Full Text Available The dense microbial communities commonly associated with plants and animals should offer many opportunities for horizontal gene transfer (HGT through described mechanisms of DNA exchange including natural transformation. However, studies of the significance of natural transformation have focused primarily on pathogens. The study presented here demonstrates highly efficient DNA exchange by natural transformation in a common symbiont of earthworms. The obligate bacterial symbiont Verminephrobacter eiseniae is a member of a microbial consortium of the earthworm Eisenia fetida that is transmitted into the egg capsules to colonize the embryonic worms. In the study presented here, by testing for transformants under different conditions in culture, we demonstrate that V. eiseniae can incorporate free DNA from the environment, that competency is regulated by environmental factors, and that it is sequence specific. Mutations in the type IV pili of V. eiseniae resulted in loss of DNA uptake, implicating the type IV pilus (TFP apparatus in DNA uptake. Furthermore, injection of DNA carrying antibiotic-resistance genes into egg capsules resulted in transformants within the capsule, demonstrating the relevance of DNA uptake within the earthworm system. The ability to take up species-specific DNA from the environment may explain the maintenance of the relatively large, intact genome of this long-associated obligate symbiont, and provides a mechanism for acquisition of foreign genes within the earthworm system.

  16. Mediation misgivings: ambiguous clinical and public health interpretations of natural direct and indirect effects.

    Science.gov (United States)

    Naimi, Ashley I; Kaufman, Jay S; MacLehose, Richard F

    2014-10-01

    Recent methodological innovation is giving rise to an increasing number of applied papers in medical and epidemiological journals in which natural direct and indirect effects are estimated. However, there is a longstanding debate on whether such effects are relevant targets of inference in population health. In light of the repeated calls for a more pragmatic and consequential epidemiology, we review three issues often raised in this debate: (i) the use of composite cross-world counterfactuals and the need for cross-world independence assumptions; (ii) interventional vs non-interventional identifiability; and (iii) the interpretational ambiguity of natural direct and indirect effect estimates. We use potential outcomes notation and directed acyclic graphs to explain 'cross-world' assumptions, illustrate implications of this assumption via regression models and discuss ensuing issues of interpretation. We argue that the debate on the relevance of natural direct and indirect effects rests on whether one takes as a target of inference the mathematical object per se, or the change in the world that the mathematical object represents. We further note that public health questions may be better served by estimating controlled direct effects. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

  17. Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Md. Asiful Islam

    2016-01-01

    Full Text Available Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA, diabetes mellitus (DM, and cardiovascular disease (CVD. Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.

  18. Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases.

    Science.gov (United States)

    Islam, Md Asiful; Alam, Fahmida; Solayman, Md; Khalil, Md Ibrahim; Kamal, Mohammad Amjad; Gan, Siew Hua

    2016-01-01

    Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro , in vivo , and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described.

  19. Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation

    Directory of Open Access Journals (Sweden)

    Chao-Yang Lai

    2017-01-01

    Full Text Available Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs, particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis. Several immune modulatory oligonucleotides and small molecular weight compounds, including IMO-3100, IMO-8400, and CPG-52364, that block the interaction between endosomal TLRs and their ligands are under clinical investigation for their effectiveness in the treatment of psoriasis. In addition, several chemical compounds, including AS-2444697, PF-05387252, PF-05388169, PF-06650833, ML120B, and PHA-408, can inhibit TLR signaling. Although these compounds have demonstrated anti-inflammatory activity in animal models, their therapeutic potential for the treatment of psoriasis has not yet been tested. Recent studies demonstrated that natural compounds derived from plants, fungi, and bacteria, including mustard seed, Antrodia cinnamomea extract, curcumin, resveratrol, thiostrepton, azithromycin, and andrographolide, inhibited psoriasis-like inflammation induced by the TLR7 agonist imiquimod in animal models. These natural modulators employ different mechanisms to inhibit endosomal TLR activation and are administered via different routes. Therefore, they represent candidate psoriasis drugs and might lead to the development of new treatment options.

  20. Dietary Phytochemicals: Natural Swords Combating Inflammation and Oxidation-Mediated Degenerative Diseases

    Science.gov (United States)

    2016-01-01

    Cumulatively, degenerative disease is one of the most fatal groups of diseases, and it contributes to the mortality and poor quality of life in the world while increasing the economic burden of the sufferers. Oxidative stress and inflammation are the major pathogenic causes of degenerative diseases such as rheumatoid arthritis (RA), diabetes mellitus (DM), and cardiovascular disease (CVD). Although a number of synthetic medications are used to treat these diseases, none of the current regimens are completely safe. Phytochemicals (polyphenols, carotenoids, anthocyanins, alkaloids, glycosides, saponins, and terpenes) from natural products such as dietary fruits, vegetables, and spices are potential sources of alternative medications to attenuate the oxidative stress and inflammation associated with degenerative diseases. Based on in vitro, in vivo, and clinical trials, some of these active compounds have shown good promise for development into novel agents for treating RA, DM, and CVD by targeting oxidative stress and inflammation. In this review, phytochemicals from natural products with the potential of ameliorating degenerative disease involving the bone, metabolism, and the heart are described. PMID:27721914

  1. The importance of nature's invisible fabric: food web structure mediates modeled responses to river restoration

    Science.gov (United States)

    Bellmore, R.; Benjamin, J.; Newsom, M.; Bountry, J.; Dombroski, D.

    2016-12-01

    Restoration is frequently aimed at the recovery of target species, but also influences the larger food web in which these species participate. Effects of restoration on this broader network of organisms can influence target species both directly and indirectly via changes in energy flow through food webs. To help incorporate these complexities into river restoration planning we constructed a food web model that links river food web dynamics to in-stream physical habitat and riparian vegetation conditions. We present an application of this model to the Methow River, Washington (USA), a location of on-going restoration aimed at recovering salmon. Three restoration strategies were simulated: riparian vegetation restoration, nutrient augmentation via salmon carcass addition, and floodplain reconnection. To explore how food web structure mediates responses to these actions, we modified the food web by adding populations of invasive aquatic snails and nonnative fish. Simulations suggest that floodplain reconnection may be a better strategy than carcass addition and vegetation planting for improving conditions for salmon in this river segment. However, modeled responses were strongly sensitive to changes in the structure of the food web. The addition of invasive snails and nonnative fishes modified pathways of energy through the food web, which negated restoration improvements. This finding illustrates that forecasting responses to restoration may require accounting for the structure of food webs, and that changes in this structure—as might be expected with the spread of invasive species—could compromise restoration outcomes. By elucidating the direct and indirect pathways by which restoration affects target species, dynamic food web models can improve restoration planning by fostering a deeper understanding of system connectedness and dynamics.

  2. Outdoor activities and depressive symptoms in displaced older adults following natural disaster: community cohesion as mediator and moderator.

    Science.gov (United States)

    Chao, Shiau-Fang

    2016-09-01

    This investigation examined whether community cohesion mediates or moderates the relationship between outdoor activities and depressive symptoms in older adults displaced by Typhoon Morakot in Taiwan. This cross-sectional study included 292 adults aged 65 years or older who were relocated to permanent houses after Typhoon Morakot damaged their homes on 8th August 2009. Multiple regression analysis was applied to test the role of community cohesion on the association between outdoor activities and depressive symptoms. The sample of displaced older adults displayed higher prevalence of depressive symptoms than the average for community dwelling older people in Taiwan. Community cohesion fully mediated the relationship between outdoor activities and depressive symptoms. Community cohesion also moderated the relationship between outdoor activities and depressive symptoms. Community cohesion occupies a key role on the link between outdoor activities and depressive symptoms. Participation in outdoor activities was associated positively with community cohesion, while high community cohesion was related negatively to depressive symptoms. Additionally, the benefit of outdoor activities to fewer depressive symptoms only manifested in older adults with high community cohesion. Programs and services should be designed to enhance community cohesion in order to maximize the benefit of outdoor activities to the mental health of displaced older adults after natural disasters.

  3. Second mitochondria-derived activator of caspase (SMAC) mimetic potentiates tumor susceptibility toward natural killer cell-mediated killing.

    Science.gov (United States)

    Brinkmann, Kerstin; Hombach, Andreas; Seeger, Jens Michael; Wagner-Stippich, Diana; Klubertz, Daniela; Krönke, Martin; Abken, Hinrich; Kashkar, Hamid

    2014-03-01

    Resistance to apoptosis is a hallmark of cancer, and represents an important mechanism of how tumor cells resist immune cell destruction. Mitochondria are the central regulators of the apoptotic machinery by releasing pro-apoptotic factors including cytochrome c and second mitochondria-derived activator of caspase (SMAC) upon mitochondrial outer membrane permeabilization (MOMP). Small molecules activating MOMP such as BH3 mimetics or antagonizers of the inhibitor of apoptosis proteins (IAPs) such as SMAC mimetics have recently engendered new optimism for a more individualized and effective cancer therapy. Here we show that a SMAC mimetic potentiates cancer cell killing by natural killer (NK) cells through reactivation of tumor cell apoptosis. Specifically, the SMAC mimetic enhances the susceptibility of tumor cells toward NK cell-mediated effector mechanisms involving death receptors and cytolytic granules containing perforin and granzymes by relieving caspase activity. Our data highlight for the first time the specific use of SMAC mimetics for boosting immune cell-mediated immunotherapy, representing a novel and promising approach in the treatment of cancer.

  4. Triphala and its active constituent chebulinic acid are natural inhibitors of vascular endothelial growth factor-a mediated angiogenesis.

    Directory of Open Access Journals (Sweden)

    Kai Lu

    Full Text Available Triphala churna (THL is a combination of three fruits that has been used for many years in India for the treatment of various diseases. There are now reports which indicate that THL can inhibit growth of malignant tumors in animals. However, the mechanisms by which THL mediates its anti-tumor actions are still being explored. Because vascular endothelial growth factor-A (VEGF induced angiogenesis plays a critical role in the pathogenesis of cancer, we therefore investigated whether tumor inhibitory effects of THL or its active constituents are through suppression of VEGF actions. We herein report that THL and chebulinic (CI present in THL can significantly and specifically inhibit VEGF induced angiogenesis by suppressing VEGF receptor-2 (VEGFR-2 phosphorylation. These results are of clinical significance as these inexpensive and non-toxic natural products can be used for the prevention and treatment of diseases where VEGF induced angiogenesis has an important role.

  5. A type IV pilus mediates DNA binding during natural transformation in Streptococcus pneumoniae.

    Science.gov (United States)

    Laurenceau, Raphaël; Péhau-Arnaudet, Gérard; Baconnais, Sonia; Gault, Joseph; Malosse, Christian; Dujeancourt, Annick; Campo, Nathalie; Chamot-Rooke, Julia; Le Cam, Eric; Claverys, Jean-Pierre; Fronzes, Rémi

    2013-01-01

    Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence. This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria. Transformation requires the binding and internalization of exogenous DNA, the mechanisms of which are unclear. Here, we report the discovery of a transformation pilus at the surface of competent Streptococcus pneumoniae cells. This Type IV-like pilus, which is primarily composed of the ComGC pilin, is required for transformation. We provide evidence that it directly binds DNA and propose that the transformation pilus is the primary DNA receptor on the bacterial cell during transformation in S. pneumoniae. Being a central component of the transformation apparatus, the transformation pilus enables S. pneumoniae, a major Gram-positive human pathogen, to acquire resistance to antibiotics and to escape vaccines through the binding and incorporation of new genetic material.

  6. A type IV pilus mediates DNA binding during natural transformation in Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Raphaël Laurenceau

    Full Text Available Natural genetic transformation is widely distributed in bacteria and generally occurs during a genetically programmed differentiated state called competence. This process promotes genome plasticity and adaptability in Gram-negative and Gram-positive bacteria. Transformation requires the binding and internalization of exogenous DNA, the mechanisms of which are unclear. Here, we report the discovery of a transformation pilus at the surface of competent Streptococcus pneumoniae cells. This Type IV-like pilus, which is primarily composed of the ComGC pilin, is required for transformation. We provide evidence that it directly binds DNA and propose that the transformation pilus is the primary DNA receptor on the bacterial cell during transformation in S. pneumoniae. Being a central component of the transformation apparatus, the transformation pilus enables S. pneumoniae, a major Gram-positive human pathogen, to acquire resistance to antibiotics and to escape vaccines through the binding and incorporation of new genetic material.

  7. Interleukin-17D Mediates Tumor Rejection through Recruitment of Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Timothy O’Sullivan

    2014-05-01

    Full Text Available The process of cancer immunoediting generates a repertoire of cancer cells that can persist in immune-competent hosts. In its most complex form, this process begins with the elimination of highly immunogenic unedited tumor cells followed by the escape of less immunogenic edited cells. Although edited tumors can release immunosuppressive factors, it is unknown whether unedited tumors produce cytokines that enhance antitumor function. Utilizing gene microarray analysis, we found the cytokine interleukin 17D (IL-17D was highly expressed in certain unedited tumors but not in edited mouse tumor cell lines. Moreover, forced expression of IL-17D in edited tumor cells induced rejection by stimulating MCP-1 production from tumor endothelial cells, leading to the recruitment of natural killer (NK cells. NK cells promoted M1 macrophage development and adaptive immune responses. IL-17D expression was also decreased in certain high-grade and metastatic human tumors, suggesting that it can be targeted for tumor immune therapy.

  8. Natural soil mediated photo Fenton-like processes in treatment of pharmaceuticals: Batch and continuous approach.

    Science.gov (United States)

    Changotra, Rahil; Rajput, Himadri; Dhir, Amit

    2017-12-01

    This paper manifests the potential viability of soil as a cost-free catalyst in photo-Fenton-like processes for treating pharmaceuticals at large scale. Naturally available soil without any cost intensive modification was utilized as a catalyst to degrade pharmaceuticals, specifically ornidazole (ORZ) and ofloxacin (OFX). Soil was characterized and found enriched with various iron oxides like hematite, magnetite, goethite, pyrite and wustite, which contributes toward enhanced dissolution of Fe 3+ than Fe 2+ in the aqueous solution resulting in augmented rate of photo-Fenton reaction. The leached iron concentration in solution was detected during the course of experiments. The degradation of ORZ and OFX was assessed in solar induced batch experiments using H 2 O 2 as oxidant and 95% ORZ and 92% OFX removal was achieved. Elevated efficiencies were achieved due to Fe 2+ /Fe 3+ cycling, producing more hydroxyl radical leading to the existence of homogeneous and heterogeneous reactions simultaneously. The removal efficiency of solar photo-Fenton like process was also compared to photo-Fenton process with different irradiation sources (UV-A and UV-B) and were statistically analysed. Continuous-scale studies were conducted employing soil either in the form of soil beads or as a thin layer spread on the surface of baffled reactor. Soil beads were found to have satisfactory reusability and stability. 84 and 79% degradation of ORZ and OFX was achieved using soil as thin layer while with soil beads 71 and 68% degradation, respectively. HPLC and TOC study confirmed the efficient removal of both the compounds. Toxicity assessment demonstrates the inexistence of toxic intermediates during the reaction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Instream cover and shade mediate avian predation on trout in semi-natural streams

    Science.gov (United States)

    Penaluna, Brooke E.; Dunham, Jason B.; Noakes, David L. G.

    2015-01-01

    Piscivory by birds can be significant, particularly on fish in small streams and during seasonal low flow when available cover from predators can be limited. Yet, how varying amounts of cover may change the extent of predation mortality from avian predators on fish is not clear. We evaluated size-selective survival of coastal cutthroat trout (Oncorhynchus clarkii clarkii) in replicated semi-natural stream sections. These sections provided high (0.01 m2 of cover per m2 of stream) or low (0.002 m2 of cover per m2 of stream) levels of instream cover available to trout and were closed to emigration. Each fish was individually tagged, allowing us to track retention of individuals during the course of the 36-day experiment, which we attributed to survival from predators, because fish had no other way to leave the streams. Although other avian predators may have been active in our system and not detected, the only predator observed was the belted kingfisher Megaceryle alcyon, which is known to prey heavily on fish. In both treatments, trout >20.4 cm were not preyed upon indicating an increased ability to prey upon on smaller individuals. Increased availability of cover improved survival of trout by 12% in high relative to low cover stream sections. Trout also survived better in stream sections with greater shade, a factor we could not control in our system. Collectively, these findings indicate that instream cover and shade from avian predators can play an important role in driving survival of fish in small streams or during periods of low flow.

  10. Natural selection acts in opposite ways on correlated hormonal mediators of prenatal maternal effects in a wild bird population.

    Science.gov (United States)

    Tschirren, Barbara; Postma, Erik; Gustafsson, Lars; Groothuis, Ton G G; Doligez, Blandine

    2014-10-01

    Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long-term data on a wild collared flycatcher (Ficedula albicollis) population, we show that natural selection acts in opposite ways on two maternally derived androgens, yolk androstenedione (A4) and yolk testosterone (T). High yolk A4 concentrations are associated with higher fitness, whereas high yolk T concentrations are associated with lower fitness. Natural selection thus favours females that produce eggs with high A4 and low T concentrations. Importantly, however, there exists a positive (non-genetic) correlation between A4 and T, which suggests that females are limited in their ability to reach this adaptive optimum. Thereby, these results provide strong evidence for an adaptive value of differential maternal androgen deposition, and a mechanistic explanation for the maintenance of variation in maternal investment in the wild. © 2014 John Wiley & Sons Ltd/CNRS.

  11. Proliferation of uterine natural killer cells is induced by human chorionic gonadotropin and mediated via the mannose receptor.

    Science.gov (United States)

    Kane, Nicole; Kelly, Rodney; Saunders, Philippa T K; Critchley, Hilary O D

    2009-06-01

    The endometrial lining of the human uterus contains a population of phenotypically distinct (CD56(bright), CD16(dim)), tissue-specific, natural killer [uterine natural killer (uNK)] cells that play a key role in the establishment of a successful pregnancy. An increase in the number of endometrial uNK cells occurs when the conceptus implants, and there is a further increase during the early stages of placentation. Here, we describe studies that have identified human chorionic gonadotrophin (hCG), a glycoprotein synthesized by the preimplantation conceptus, as a novel regulator of uNK cell proliferation. The impact of hCG on uNK cells was mediated via the mannose receptor (CD206) rather than by the classical hCG/LH receptor that was not expressed. The mannose receptor and hCG were colocalized on the surface of uNK cells, and proliferation did not occur if cells were incubated with deglycosylated hCG or intact hCG in the presence of excess d-Mannose. These novel observations provide new insight into the endocrine-immune dialogue that exists between the conceptus and immune cells within the receptive endometrium, and have implications for the role of uNK cell-trophoblast interactions and pregnancy outcome.

  12. Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis

    Science.gov (United States)

    Bobat, Saeeda; Darby, Matthew; Mrdjen, Dunja; Cook, Charlotte; Logan, Erin; Auret, Jennifer; Jones, Elizabeth; Schnoeller, Corinna; Flores-Langarica, Adriana; Ross, Ewan A.; Vira, Alykhan; López-Macías, Constantino; Henderson, Ian R.; Alexander, James; Brombacher, Frank; Horsnell, William G.; Cunningham, Adam F.

    2014-01-01

    that co-infection can radically alter the development of protective immunity during natural infection and in response to immunization. PMID:25474738

  13. Relationship between atherosclerosis and occlusal support of natural teeth with mediating effect of atheroprotective nutrients: From the SONIC study

    Science.gov (United States)

    Tada, Sayaka; Kamide, Kei; Gondo, Yasuyuki; Inomata, Chisato; Takeshita, Hajime; Matsuda, Ken-ich; Kitamura, Masahiro; Murakami, Shinya; Kabayama, Mai; Oguro, Ryousuke; Nakama, Chikako; Kawai, Tatsuo; Yamamoto, Koichi; Sugimoto, Ken; Shintani, Ayumi; Ishihara, Takuma; Arai, Yasumichi; Masui, Yukie; Takahashi, Ryutaro; Rakugi, Hiromi; Maeda, Yoshinobu

    2017-01-01

    Whereas most of studies investigating relationship between oral health and atherosclerosis have focused on periodontitis, very few of them were examined about occlusal status of natural teeth which possibly influence dietary habit. The primary aim of this cross-sectional study was to investigate the association between the occlusal support of posterior teeth and the prevalence of atherosclerosis in community-dwelling septuagenarians. Also, the second aim was to test the hypothesis that the intake of key nutrients for atherosclerosis prevention would have a mediating effect on the relationship between the occlusal status and atherosclerosis. The study population included 468 community-dwelling dentate persons aged 69–71 years recruited from the local residential registration in Japan. Participants were divided into three groups, according to the number of occlusal support zones (OSZ) in the posterior area: Complete (four OSZ), Moderate (three or two OSZ), and Collapsed (one or no OSZ). Dietary intakes were assessed using a brief-type self-administered diet history questionnaire. Atherosclerosis was defined as carotid intima-media thickness ≧1.10 mm by using carotid ultrasonography test. The logistic or linear regression model was used in multivariate analysis to assess relationship between occlusal status and atherosclerosis, and the mediating effect of key nutrients within the relationship. Multivariable analysis showed a significant association between occlusal status and atherosclerosis (odds ratio for Collapsed group to Complete group: 1.87; 95% CI: 1.45–2.41), independent of periodontal status (odds ratio: 2.01, 95%CI: 1.46–2.78). Fish and shellfish, vitamin B6 and n-3PUFAs were significantly related to both of occlusal status and atherosclerosis, and also was indicated a mediating effect on the association between occlusal status and atherosclerosis. This study implied that, within the limitation of the cross-sectional study design, the reduced

  14. (1)H, (13)C and (15)N NMR assignments for N- and O-acylethanolamines, important family of naturally occurring bioactive lipid mediators.

    Science.gov (United States)

    Ottria, Roberta; Casati, Silvana; Ciuffreda, Pierangela

    2012-12-01

    The complete (1)H, (13)C and (15)N NMR signal assignments of some N- and O-acylethanolamines, important family of naturally occurring bioactive lipid mediators, were achieved using one-dimensional and two-dimensional experiments (gs-HMQC and gs-HMBC). Copyright © 2012 John Wiley & Sons, Ltd.

  15. A case-study of ontology-driven semantic mediation of flower-visiting data from heterogeneous data-stores in three South African natural history collections

    CSIR Research Space (South Africa)

    Coetzer, W

    2013-05-01

    Full Text Available -study of ontology-driven semantic mediation using records of flower-visiting insects from three natural history collections in South Africa. We establish a conceptual domain model for flower-visiting, expressed in an OWL ontology, and use it to semantically enrich...

  16. Natural products mediating ecological interactions in Antarctic benthic communities: a mini-review of the known molecules.

    Science.gov (United States)

    Núñez-Pons, L; Avila, C

    2015-07-01

    Out of the many bioactive compounds described from the oceans, only a small fraction have been studied for their ecological significance. Similarly, most chemically mediated interactions are not well understood, because the molecules involved remain unrevealed. In Antarctica, this gap in knowledge is even more acute in comparison to tropical or temperate regions, even though polar organisms are also prolific producers of chemical defenses, and pharmacologically relevant products are being reported from the Southern Ocean. The extreme and unique marine environments surrounding Antarctica along with the numerous unusual interactions taking place in benthic communities are expected to select for novel functional secondary metabolites. There is an urgent need to comprehend the evolutionary role of marine derived substances in general, and particularly at the Poles, since molecules of keystone significance are vital in species survival, and therefore, in structuring the communities. Here we provide a mini-review on the identified marine natural products proven to have an ecological function in Antarctic ecosystems. This report recapitulates some of the bibliography from original Antarctic reviews, and updates the new literature in the field from 2009 to the present.

  17. Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells

    Science.gov (United States)

    Benson, Don M.; Yu, Jianhua; Becknell, Brian; Wei, Min; Freud, Aharon G.; Ferketich, Amy K.; Trotta, Rossana; Perrotti, Danilo; Briesewitz, Roger

    2009-01-01

    Stem cell factor (SCF) promotes synergistic cellular proliferation in combination with several growth factors, and appears important for normal natural killer (NK)–cell development. CD34+ hematopoietic precursor cells (HPCs) require interleukin-15 (IL-15) for differentiation into human NK cells, and this effect can be mimicked by IL-2. Culture of CD34+ HPCs or some primary human NK cells in IL-2/15 and SCF results in enhanced growth compared with either cytokine alone. The molecular mechanisms responsible for this are unknown and were investigated in the present work. Activation of NK cells by IL-2/15 increases expression of c-kit whose kinase activity is required for synergy with IL-2/15 signaling. Mitogen-activated protein kinase (MAPK) signaling intermediaries that are activated both by SCF and IL-2/15 are enhanced in combination to facilitate earlier cell-cycle entry. The effect results at least in part via enhanced MAPK-mediated modulation of p27 and CDK4. Collectively the data reveal a novel mechanism by which SCF enhances cellular proliferation in combination with IL-2/15 in primary human NK cells. PMID:19060242

  18. Natural killer (NK cell mediated antibody-dependent cellular cytotoxicity (ADCC in tumour immunotherapy with therapeutic antibodies

    Directory of Open Access Journals (Sweden)

    Ursula Jördis Eva Seidel

    2013-03-01

    Full Text Available In the last decade several therapeutic antibodies have been FDA and EMEA approved. Although their mechanisms of action in vivo is not fully elucidated, antibody-dependent cellular cytotoxicity (ADCC mediated by natural killer (NK cells is presumed to be a key effector function. A substantial role of ADCC has been demonstrated in vitro and in mouse tumour models. However, a direct in vivo effect of ADCC in tumour reactivity in humans remains to be shown. Several studies revealed a predictive value of FcγRIIIa-V158F polymorphism in monoclonal antibody treatment, indicating a potential effect of ADCC on outcome for certain indications. Furthermore, the use of therapeutic antibodies after allogeneic haematopoietic stem cell transplantation is an interesting option. Studying the role of the FcγRIIIa-V158F polymorphism and the influence of KIR-receptor-ligand incompatibility on ADCC in this approach may contribute to future transplantation strategies. Despite the success of approved second-generation antibodies in the treatment of several malignancies, efforts are made to further augment ADCC in vivo by antibody engineering. Here, we review currently used therapeutic antibodies for which ADCC has been suggested as effector function.

  19. natural

    Directory of Open Access Journals (Sweden)

    Elías Gómez Macías

    2006-01-01

    Full Text Available Partiendo de óxido de magnesio comercial se preparó una suspensión acuosa, la cual se secó y calcinó para conferirle estabilidad térmica. El material, tanto fresco como usado, se caracterizó mediante DRX, área superficial BET y SEM-EPMA. El catalizador mostró una matriz de MgO tipo periclasa con CaO en la superficie. Las pruebas de actividad catalítica se efectuaron en lecho fijo empacado con partículas obtenidas mediante prensado, trituración y clasificación del material. El flujo de reactivos consistió en mezclas gas natural-aire por debajo del límite inferior de inflamabilidad. Para diferentes flujos y temperaturas de entrada de la mezcla reactiva, se midieron las concentraciones de CH4, CO2 y CO en los gases de combustión con un analizador de gases tipo infrarrojo no dispersivo (NDIR. Para alcanzar conversión total de metano se requirió aumentar la temperatura de entrada al lecho a medida que se incrementó el flujo de gases reaccionantes. Los resultados obtenidos permiten desarrollar un sistema de combustión catalítica de bajo costo con un material térmicamente estable, que promueva la alta eficiencia en la combustión de gas natural y elimine los problemas de estabilidad, seguridad y de impacto ambiental negativo inherentes a los procesos de combustión térmica convencional.

  20. Improved enzyme-mediated synthesis and supramolecular self-assembly of naturally occurring conjugates of β-sitosterol.

    Science.gov (United States)

    Wimmerová, Martina; Siglerová, Věra; Šaman, David; Šlouf, Miroslav; Kaletová, Eva; Wimmer, Zdeněk

    2017-01-01

    Naturally occurring acylated β-sitosteryl glucosides have been investigated for their novel properties. The synthetic protocol based on the literature data was improved and optimized. The main improvement consists in employing systems of ionic liquids combined with organic solvents in lipase-mediated esterification of (3β)-stigmast-5-en-3-yl β-d-glucopyranoside to get (3β)-stigmast-5-en-3-yl 6-O-acyl-β-d-glucopyranosides. Maximum yields of these products were achieved with Candida antarctica lipase B immobilized on Immobead 150, recombinant from yeast, in absolute THF and in the presence of either ionic liquid [1-butyl-3-methyl imidazolium tetrafluoroborate ([BMIM]BF 4 ) or 1-butyl-3-methyl imidazolium hexafluorophosphate ([BMIM]PF 6 )] employed. Pharmacological activity of (3β)-stigmast-5-en-3-yl 6-O-acyl-β-d-glucopyranosides was studied in tests on MCF7 tumor cell lines; the compounds displayed moderate activity which was higher than the activity of β-sitosterol. Supramolecular characteristics were discovered at (3β)-stigmast-5-en-3-yl 6-O-dodecanoyl-β-d-glucopyranoside that formed supramolecular polymer through multiple H-bonds in a methanol/water system (60/40). Its formation was confirmed by the independent UV-vis measurements during certain time period, by variable temperature DOSY-NMR measurement in deuteriochloroform, and visualized by transmission electron microscopy (TEM) and atomic force microscopy (AFM) showing chiral helical structures and complex superassembly systems based on fibrous supramolecular polymer. In contrary, no such properties have been observed for the other two (3β)-stigmast-5-en-3-yl 6-O-acyl-β-d-glucopyranosides under the given experimental conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Natural selection acts in opposite ways on correlated hormonal mediators of prenatal maternal effects in a wild bird population

    NARCIS (Netherlands)

    Tschirren, Barbara; Postma, Erik; Gustafsson, Lars; Groothuis, Ton G. G.; Doligez, Blandine

    2014-01-01

    Maternal hormones are important mediators of prenatal maternal effects. Although many experimental studies have demonstrated their potency in shaping offspring phenotypes, we know remarkably little about their adaptive value. Using long-term data on a wild collared flycatcher (Ficedula albicollis)

  2. Monsters or Good Guys: The Mediating Role of Emotions in Transforming a Young Child's Encounter with Nature

    Science.gov (United States)

    Green, Carrie

    2016-01-01

    Nature-play inspires a sense of awe and wonder in young children, however, the uncertainty of elements in nature can also bring about fear and anxiety. Using sensory tours as a data collection method, this qualitative study explores the emotions of a four-year-old during his exploration of an imaginary "monster castle" in the forest, and…

  3. Natural history-driven, plant-mediated RNAi-based study reveals CYP6B46’s role in a nicotine-mediated antipredator herbivore defense

    Science.gov (United States)

    Kumar, Pavan; Pandit, Sagar S.; Steppuhn, Anke; Baldwin, Ian T.

    2014-01-01

    Manduca sexta (Ms) larvae are known to efficiently excrete ingested nicotine when feeding on their nicotine-producing native hostplant, Nicotiana attenuata. Here we describe how ingested nicotine is co-opted for larval defense by a unique mechanism. Plant-mediated RNAi was used to silence a midgut-expressed, nicotine-induced cytochrome P450 6B46 (CYP6B46) in larvae consuming transgenic N. attenuata plants producing MsCYP6B46 dsRNA. These and transgenic nicotine-deficient plants were planted into native habitats to study the phenotypes of larvae feeding on these plants and the behavior of their predators. The attack-behavior of a native wolf spider (Camptocosa parallela), a major nocturnal predator, provided the key to understanding MsCYP6B46’s function: spiders clearly preferred CYP6B46-silenced larvae, just as they had preferred larvae fed nicotine-deficient plants. MsCYP6B46 redirects a small amount (0.65%) of ingested nicotine from the midgut into hemolymph, from which nicotine is exhaled through the spiracles as an antispider signal. CYP6B46-silenced larvae were more susceptible to spider-attack because they exhaled less nicotine because of lower hemolymph nicotine concentrations. CYP6B46-silenced larvae were impaired in distributing ingested nicotine from midgut to hemolymph, but not in the clearing of hemolymph nicotine or in the exhalation of nicotine from hemolymph. MsCYP6B46 could be a component of a previously hypothesized pump that converts nicotine to a short-lived, transportable, metabolite. Other predators, big-eyed bugs, and antlion larvae were insensitive to this defense. Thus, chemical defenses, too toxic to sequester, can be repurposed for defensive functions through respiration as a form of defensive halitosis, and predators can assist the functional elucidation of herbivore genes. PMID:24379363

  4. Natural history-driven, plant-mediated RNAi-based study reveals CYP6B46's role in a nicotine-mediated antipredator herbivore defense.

    Science.gov (United States)

    Kumar, Pavan; Pandit, Sagar S; Steppuhn, Anke; Baldwin, Ian T

    2014-01-28

    Manduca sexta (Ms) larvae are known to efficiently excrete ingested nicotine when feeding on their nicotine-producing native hostplant, Nicotiana attenuata. Here we describe how ingested nicotine is co-opted for larval defense by a unique mechanism. Plant-mediated RNAi was used to silence a midgut-expressed, nicotine-induced cytochrome P450 6B46 (CYP6B46) in larvae consuming transgenic N. attenuata plants producing MsCYP6B46 dsRNA. These and transgenic nicotine-deficient plants were planted into native habitats to study the phenotypes of larvae feeding on these plants and the behavior of their predators. The attack-behavior of a native wolf spider (Camptocosa parallela), a major nocturnal predator, provided the key to understanding MsCYP6B46's function: spiders clearly preferred CYP6B46-silenced larvae, just as they had preferred larvae fed nicotine-deficient plants. MsCYP6B46 redirects a small amount (0.65%) of ingested nicotine from the midgut into hemolymph, from which nicotine is exhaled through the spiracles as an antispider signal. CYP6B46-silenced larvae were more susceptible to spider-attack because they exhaled less nicotine because of lower hemolymph nicotine concentrations. CYP6B46-silenced larvae were impaired in distributing ingested nicotine from midgut to hemolymph, but not in the clearing of hemolymph nicotine or in the exhalation of nicotine from hemolymph. MsCYP6B46 could be a component of a previously hypothesized pump that converts nicotine to a short-lived, transportable, metabolite. Other predators, big-eyed bugs, and antlion larvae were insensitive to this defense. Thus, chemical defenses, too toxic to sequester, can be repurposed for defensive functions through respiration as a form of defensive halitosis, and predators can assist the functional elucidation of herbivore genes.

  5. Design of pH-sensitive peptides from natural antimicrobial peptides for enhancing polyethylenimine-mediated gene transfection.

    Science.gov (United States)

    Zhang, Shi-Kun; Song, Jin-Wen; Li, Su-Bo; Gao, Hong-Wei; Chang, Hong-Yu; Jia, Li-Li; Gong, Feng; Tan, Ying-Xia; Ji, Shou-Ping

    2017-05-01

    Poor endosomal release is a major barrier of polyplex-mediated gene transfection. Antimicrobial peptides (AMPs) are commonly used to improve polyethylenimine (PEI)-mediated gene transfection by increasing endosomal release. In the present study, we designed novel pH-sensitive peptides that highly enhance transfection efficiency compared to their parent peptides. Two analogues of melittin (Mel) and RV-23 (RV) were synthesized by replacing the positively-charged residues in their sequences with glutamic acid residues. The pH-sensitive lysis ability of the peptides, the effect of the peptides on physicochemical characteristics, the intracellular trafficking, the transfection efficiency, and the cytotoxicity of the polyplexes were determined. The acidic peptides showed pH-sensitive lytic activity. The hemolytic activity of acidic peptides at pH 5.0 was higher than that at pH 7.4. The incorporation of acidic peptides did not affect the DNA binding ability of PEI but affected the physicochemical characteristics of the PEI/DNA polyplexes, which may be beneficial for endosomal release and gene transfection. The incorporation of acidic peptides into PEI/DNA polyplexes enhanced the PEI-mediated transfection efficiency corresponding to up to 42-fold higher luciferase activity compared to that of PEI alone. The results of the present study indicate that replacement of positively-charged residues with glutamic acid residues in the AMP sequence yields pH-sensitive peptides, which enhance the transfection efficiency of PEI/DNA polyplexes in various cell lines. Copyright © 2017 John Wiley & Sons, Ltd.

  6. NK-cell-dependent killing of colon carcinoma cells is mediated by natural cytotoxicity receptors (NCRs) and stimulated by parvovirus infection of target cells

    International Nuclear Information System (INIS)

    Bhat, Rauf; Rommelaere, Jean

    2013-01-01

    Investigating how the immune system functions during malignancies is crucial to developing novel therapeutic strategies. Natural killer (NK) cells, an important component of the innate immune system, play a vital role in immune defense against tumors and virus-infected cells. The poor survival rate in colon cancer makes it particularly important to develop novel therapeutic strategies. Oncolytic viruses, in addition to lysing tumor cells, may have the potential to augment antitumor immune responses. In the present study, we investigate the role of NK cells and how parvovirus H-1PV can modulate NK-cell mediated immune responses against colon carcinoma. Human NK cells were isolated from the blood of healthy donors. The cytotoxicity and antibody-mediated inhibition of NK cells were measured in chromium release assays. Phenotypic assessment of colon cancer and dendritic cells was done by FACS. The statistical significance of the results was calculated with Student’s t test (*p <0.05; **, p < 0.01; ***, p < 0.001). We show that IL-2-activated human NK cells can effectively kill colon carcinoma cells. Killing of colon carcinoma cells by NK cells was further enhanced upon infection of the former cells with parvovirus H-1PV. H-1PV has potent oncolytic activity against various tumors, yet its direct killing effect on colon carcinoma cells is limited. The cytotoxicity of NK cells towards colon carcinoma cells, both mock- and H-1PV-infected, was found to be mostly mediated by a combination of natural cytotoxicity receptors (NCRs), namely NKp30, 44, and 46. Colon carcinoma cells displayed low to moderate expression of NK cell ligands, and this expression was modulated upon H-1PV infection. Lysates of H-1PV-infected colon carcinoma cells were found to increase MHC class II expression on dendritic cells. Altogether, these data suggest that IL-2-activated NK cells actively kill colon carcinoma cells and that this killing is mediated by several natural cytotoxicity receptors

  7. Multiplexed CRISPR/Cas9- and TAR-Mediated Promoter Engineering of Natural Product Biosynthetic Gene Clusters in Yeast.

    Science.gov (United States)

    Kang, Hahk-Soo; Charlop-Powers, Zachary; Brady, Sean F

    2016-09-16

    The use of DNA sequencing to guide the discovery of natural products has emerged as a new paradigm for revealing chemistries encoded in bacterial genomes. A major obstacle to implementing this approach to natural product discovery is the transcriptional silence of biosynthetic gene clusters under laboratory growth conditions. Here we describe an improved yeast-based promoter engineering platform (mCRISTAR) that combines CRISPR/Cas9 and TAR to enable single-marker multiplexed promoter engineering of large gene clusters. mCRISTAR highlights the first application of the CRISPR/Cas9 system to multiplexed promoter engineering of natural product biosynthetic gene clusters. In this method, CRISPR/Cas9 is used to induce DNA double-strand breaks in promoter regions of biosynthetic gene clusters, and the resulting operon fragments are reassembled by TAR using synthetic gene-cluster-specific promoter cassettes. mCRISTAR uses a CRISPR array to simplify the construction of a CRISPR plasmid for multiplex CRISPR and a single auxotrophic selection to improve the inefficiency of using a CRISPR array for multiplex gene cluster refactoring. mCRISTAR is a simple and generic method for multiplexed replacement of promoters in biosynthetic gene clusters that will facilitate the discovery of natural products from the rapidly growing collection of gene clusters found in microbial genome and metagenome sequencing projects.

  8. The natural product phyllanthusmin C enhances IFN-γ production by human NK cells through upregulation of TLR-mediated NF-κB signaling.

    Science.gov (United States)

    Deng, Youcai; Chu, Jianhong; Ren, Yulin; Fan, Zhijin; Ji, Xiaotian; Mundy-Bosse, Bethany; Yuan, Shunzong; Hughes, Tiffany; Zhang, Jianying; Cheema, Baljash; Camardo, Andrew T; Xia, Yong; Wu, Lai-Chu; Wang, Li-Shu; He, Xiaoming; Kinghorn, A Douglas; Li, Xiaohui; Caligiuri, Michael A; Yu, Jianhua

    2014-09-15

    Natural products are a major source for cancer drug development. NK cells are a critical component of innate immunity with the capacity to destroy cancer cells, cancer-initiating cells, and clear viral infections. However, few reports describe a natural product that stimulates NK cell IFN-γ production and unravel a mechanism of action. In this study, through screening, we found that a natural product, phyllanthusmin C (PL-C), alone enhanced IFN-γ production by human NK cells. PL-C also synergized with IL-12, even at the low cytokine concentration of 0.1 ng/ml, and stimulated IFN-γ production in both human CD56(bright) and CD56(dim) NK cell subsets. Mechanistically, TLR1 and/or TLR6 mediated PL-C's activation of the NF-κB p65 subunit that in turn bound to the proximal promoter of IFNG and subsequently resulted in increased IFN-γ production in NK cells. However, IL-12 and IL-15Rs and their related STAT signaling pathways were not responsible for the enhanced IFN-γ secretion by PL-C. PL-C induced little or no T cell IFN-γ production or NK cell cytotoxicity. Collectively, we identify a natural product with the capacity to selectively enhance human NK cell IFN-γ production. Given the role of IFN-γ in immune surveillance, additional studies to understand the role of this natural product in prevention of cancer or infection in select populations are warranted. Copyright © 2014 by The American Association of Immunologists, Inc.

  9. Ruthenium Nanoparticles Mediated Electrocatalytic Reduction of UO22+Ions for Its Rapid and Sensitive Detection in Natural Waters.

    Science.gov (United States)

    Gupta, Ruma; Sundararajan, Mahesh; Gamare, Jayashree S

    2017-08-01

    Reduction of UO 2 2+ ions to U 4+ ions is difficult due to involvement of two axially bonded oxygen atoms, and often requires a catalyst to lower the activation barrier. The noble metal nanoparticles (NPs) exhibit high electrocatalytic activity, and could be employed for the sensitive and rapid quantifications of U0 2 2+ ions in the aqueous matrix. Therefore, the Pd, Ru, and Rh NPs decorated glassy carbon electrode were examined for their efficacy toward electrocatalytic reduction of UO 2 2+ ions and observed that Ru NPs mediate efficiently the electro-reduction of UO 2 2+ ions. The mechanism of the electroreduction of UO 2 2+ by the RuNPs/GC was studied using density functional theory calculations which pointed different approach of 5f metal ions electroreduction unlike 4p metal ions such as As(III). RuNP decorated on the glassy carbon would be hydrated, which in turn assist to adsorb the uranyl sulfates through hydrogen bonding thus facilitated electro-reduction. Differential pulse voltammetric (DPV) technique, was used for rapid and sensitive quantification of UO 2 2+ ions. The RuNPs/GC based DPV technique could be used to determine the concentration of uranyl in a few minutes with a detection limit of 1.95 ppb. The RuNPs/GC based DPV was evaluated for its analytical performance using seawater as well lake water and groundwater spiked with known amounts of UO 2 2+ .

  10. Natural killer cell activation distinguishes Mycobacterium tuberculosis-mediated immune reconstitution syndrome from chronic HIV and HIV/MTB coinfection.

    Science.gov (United States)

    Conradie, Francesca; Foulkes, Andrea S; Ive, Prudence; Yin, Xiangfan; Roussos, Katerina; Glencross, Deborah K; Lawrie, Denise; Stevens, Wendy; Montaner, Luis J; Sanne, Ian; Azzoni, Livio

    2011-11-01

    With increased access to antiretroviral treatment (ART), immune reconstitution inflammatory syndrome (IRIS) in Mycobacterium tuberculosis (MTB)-infected populations remains a clinical challenge. We studied a cross-sectional cohort of HIV-infected subjects in Johannesburg (South Africa) to help define the immune correlates that best distinguish IRIS from ongoing MTB cases. We studied HIV+ subjects developing MTB-related unmasking tuberculosis-related immune reconstitution inflammatory syndrome (uTB-IRIS) after ART initiation; control groups were subjects with HIV and HIV/tuberculosis-coinfected subjects with comparable ART treatment. Testing was conducted with whole blood-based 4-color flow cytometry and plasma-based Luminex cytokine assessment. Natural killer cell activation, C-reactive protein, and interleukin 8 serum concentration were significantly higher in uTB-IRIS subjects compared with both control groups. In addition, all MTB-coinfected subjects, independent of clinical presentation, had higher neutrophils and T-cell activation, together with lower lymphocytes, CD4⁺ T-cell, and myeloid dendritic cell counts. Using conditional inference tree analysis, we show that elevated natural killer cell activation in combination with lymphocyte count characterizes the immunological profile of uTB-IRIS. Our results support a role for innate immune effectors in the immunopathogenesis of unmasking MTB-related IRIS and identify new immune parameters defining this pathology.

  11. The impact of HLA class I-specific killer cell immunoglobulin-like receptors on antibody-dependent natural killer cell-mediated cytotoxicity and organ allograft rejection

    Directory of Open Access Journals (Sweden)

    Raja Rajalingam

    2016-12-01

    Full Text Available Natural killer (NK cells of the innate immune system are cytotoxic lymphocytes that play important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self HLA class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIR is involved in the calibration of NK cell effector capacities during a developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self HLA class I (due to virus infection or tumor transformation or HLA class I disparities (in the setting of allogeneic transplantation. NK cells expressing an inhibitory KIR binding self HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC, triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

  12. Nature of the suppressor cells mediating prolonged graft survival after administration of extracted histocompatibility antigen and cyclosporine

    International Nuclear Information System (INIS)

    Yoshimura, N.; Kahan, B.D.

    1985-01-01

    Antigen-specific suppressor T cells are induced by donor histocompatibility antigen extracted from spleen cells with 3M KCl combined with cyclosporine (Ag-CsA). A single i.v. injection of 5 mg 3M-KCl-extracted donor Buffalo (Buf, RT1b) antigen (Ag) combined with a three day course of CsA prolonged renal allograft survival in Wistar-Furth (WFu, RT1u) hosts to a greater extent (MST 26.5 days) than CsA alone (MST 11.8 days). Peripheral blood lymphocytes (PBL) or spleen cells harvested from Ag-CsA-treated recipients ten days after transplantation inhibited the mixed lymphocyte reaction (MLR) between normal responder WFu cells and irradiated Buf cells (55.6% and 64.4% suppression, respectively, P less than 0.025), but not third-party Brown-Norway (BN, RT1n) stimulator cells (13.6% and -18.3% suppression, respectively, NS). The suppressor effect was not mediated by cytolytic cells; there was neither primary nor secondary cytolytic activity against 51 Cr-labeled Con-A blastoid Buf cells. The suppressor cells were neither adherent to plastic dishes nor to nylon-wool columns. PBL irradiated with 800 rads, but not 1500 rads, suppressed the MLR. A single injection of cyclophosphamide (CY, 25 mg/kg) seven days after transplantation abrogated the suppression induced by Ag-CsA treatment. Moreover, PBL from Ag-CsA recipients failed to suppress the MLR, if depleted either of all T cells by treatment with monoclonal antibody (Mab) W3/13 HLK (pan T cells; % suppression -15.8), or of cytotoxic/suppressor cells with Mab OX-8 (-19.3% suppression) together with rabbit antimouse immunoglobulin and complement

  13. Catalytic efficiency of natural and synthetic compounds used as laccase-mediators in oxidising veratryl alcohol and a kraft lignin, estimated by electrochemical analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez Arzola, K. [Department of Microbiology and Cell Biology, Faculty of Pharmacy, University of La Laguna, 38206 La Laguna, Tenerife (Spain); Arevalo, M.C. [Department of Physical Chemistry, Faculty of Chemistry, University of La Laguna, 38206 La Laguna, Tenerife (Spain)], E-mail: carevalo@ull.es; Falcon, M.A. [Department of Microbiology and Cell Biology, Faculty of Pharmacy, University of La Laguna, 38206 La Laguna, Tenerife (Spain)], E-mail: mafalcon@ull.es

    2009-03-30

    The electrochemical properties of eighteen natural and synthetic compounds commonly used to expand the oxidative capacity of laccases were evaluated in an aqueous buffered medium using cyclic voltammetry. This clarifies which compounds fulfil the requisites to be considered as redox mediators or enhancers. Cyclic voltammetry was also applied as a rapid way to assess the catalytic efficiency (CE) of those compounds which oxidise a non-phenolic lignin model (veratryl alcohol, VA) and a kraft lignin (KL). With the exception of gallic acid and catechol, all assayed compounds were capable of oxidising VA with varying CE. However, only some of them were able to oxidise KL. Although the oxidised forms of HBT and acetovanillone were not electrochemically stable, their reduced forms were quickly regenerated in the presence of VA. They thus act as chemical catalysts. Importantly, HBT and HPI did not attack the KL via the same mechanism as in VA oxidation. Electrochemical evidence suggests that violuric acid oxidises both substrates by an electron transfer mechanism, unlike the other N-OH compounds HBT and HPI. Acetovanillone was found to be efficient in oxidising VA and KL, even better than the synthetic mediators TEMPO, violuric acid or ABTS. Most of the compounds produced a generalised increase in the oxidative charge of KL, probably attributed to chain reactions arising between the phenolic and non-phenolic components of this complex molecule.

  14. Natural Killer Cell-Mediated Host Defense against Uropathogenic E. coli Is Counteracted by Bacterial HemolysinA-Dependent Killing of NK Cells

    Science.gov (United States)

    Gur, Chamutal; Coppenhagen-Glazer, Shunit; Rosenberg, Shilo; Yamin, Rachel; Enk, Jonatan; Glasner, Ariella; Bar-On, Yotam; Fleissig, Omer; Naor, Ronit; Abed, Jawad; Mevorach, Dror; Granot, Zvi; Bachrach, Gilad; Mandelboim, Ofer

    2013-01-01

    SUMMARY Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI. PMID:24331464

  15. Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity.

    Science.gov (United States)

    Siew, Yin-Yin; Neo, Soek-Ying; Yew, Hui-Chuing; Lim, Shun-Wei; Ng, Yi-Cheng; Lew, Si-Min; Seetoh, Wei-Guang; Seow, See-Voon; Koh, Hwee-Ling

    2015-12-01

    Selected cytotoxic chemicals can provoke the immune system to recognize and destroy malignant tumors. Most of the studies on immunogenic cell death are focused on the signals that operate on a series of receptors expressed by dendritic cells to induce tumor antigen-specific T-cell responses. Here, we explored the effects of oxaliplatin, an immunogenic cell death inducer, on the induction of stress ligands and promotion of natural killer (NK) cell-mediated cytotoxicity in human ovarian cancer cells. The results indicated that treatment of tumor cells with oxaliplatin induced the production of type I interferons and chemokines and enhanced the expression of major histocompatibility complex class I-related chains (MIC) A/B, UL16-binding protein (ULBP)-3, CD155 and TNF-related apoptosis-inducing ligand (TRAIL)-R1/R2. Furthermore, oxaliplatin but not cisplatin treatment enhanced susceptibility of ovarian cancer cells to NK cell-mediated cytolysis. In addition, activated NK cells completely abrogated the growth of cancer cells that were pretreated with oxaliplatin. However, cancer cells pretreated with the same concentration of oxaliplatin alone were capable of potentiating regrowth over a period of time. These results suggest an advantage in combining oxaliplatin and NK cell-based therapy in the treatment of ovarian cancer. Further investigation on such potential combination therapy is warranted. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Mental health consequences of international migration for Vietnamese Americans and the mediating effects of physical health and social networks: results from a natural experiment approach.

    Science.gov (United States)

    Fu, Hongyun; VanLandingham, Mark J

    2012-05-01

    Although the existing literature on immigrant mental health is extensive, major substantive and methodological gaps remain. Substantively, there is little population-based research that focuses on the mental health consequences of migration for Vietnamese Americans. More generally, although a wide range of mental health problems among immigrants has been identified, the potential causal or mediating mechanisms underlying these problems remain elusive. This latter substantive shortcoming is related to a key methodological challenge involving the potentially confounding effects of selection on migration-related outcomes. This article addresses these challenges by employing a "natural experiment" design, involving comparisons among three population-based samples of Vietnamese immigrants, never-leavers, and returnees (N=709). Data were collected in Ho Chi Minh City and in New Orleans between 2003 and 2005. The study investigates the long-term impact of international migration on Vietnamese mental health, and the potential mediating effects of social networks and physical health on these migration-related outcomes. The results reveal both mental health advantages and disadvantages among Vietnamese immigrants relative to the two groups of Vietnamese nationals. Selection can be ruled out for some of these differences, and both social networks and physical health are found to play important explanatory roles.

  17. Possible Therapeutic Application of Targeting Type II Natural Killer T Cell-Mediated Suppression of Tumor Immunity

    Science.gov (United States)

    Kato, Shingo; Berzofsky, Jay A.; Terabe, Masaki

    2018-01-01

    Natural killer T (NKT) cells are a unique T cell subset that exhibits characteristics from both the innate immune cells and T cells. There are at least two subsets of NKT cells, type I and type II. These two subsets of NKT cells have opposite functions in antitumor immunity. Type I NKT cells usually enhance and type II NKT cells suppress antitumor immunity. In addition, these two subsets of NKT cells cross-regulate each other. In this review, we mainly focus on immunosuppressive NKT cells, type II NKT cells. After summarizing their definition, experimental tools to study them, and subsets of them, we will discuss possible therapeutic applications of type II NKT cell pathway targeted therapies. PMID:29520281

  18. A Sibling-Mediated Intervention for Children with Autism Spectrum Disorder: Using the Natural Language Paradigm (NLP).

    Science.gov (United States)

    Spector, Vicki; Charlop, Marjorie H

    2017-11-23

    We taught three typically developing siblings to occasion speech by implementing the Natural Language Paradigm (NLP) with their brothers with autism spectrum disorder (ASD). A non-concurrent multiple baseline design across children with ASD and sibling dyads was used. Ancillary behaviors of happiness, play, and joint attention for the children with ASD were recorded. Generalization of speech for the children with ASD across setting and peers was also measured. During baseline, the children with ASD displayed few target speech behaviors and the siblings inconsistently occasioned speech from their brothers. After sibling training, however, they successfully delivered NLP, and in turn, for two of the brothers with ASD, speech reached criterion. Implications of this research suggest the inclusion of siblings in interventions.

  19. From sabotage to camouflage: viral evasion of cytotoxic T lymphocyte and natural killer cell-mediated immunity.

    Science.gov (United States)

    Farrell, H E; Davis-Poynter, N J

    1998-06-01

    The outcome of a virus infection is strongly influenced by interactions between host immune defences and virus 'antidefence' mechanisms. For many viruses, their continued survival depends on the speed of their attack:their capacity to replicate and transmit to uninfected hosts prior to their elimination by an effective immune response. In contrast, the success of persistent viruses lies in their capacity for immunological subterfuge: the evasion of host defence mechanism by either mutation (covered elsewhere in this issue, by Gould and Bangham, pp. 331-338) or interference with the action of host cellular proteins that are important components of the immune response. This review will focus on the strategies employed by persistent viruses against two formidable host defences against virus infection: the CD8+ cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses.

  20. A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer

    Directory of Open Access Journals (Sweden)

    Wenbo Yao

    2017-08-01

    Full Text Available Hepatocellular carcinoma (HCC is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.

  1. Mediating the potent ROS toxicity of acrolein in neurons with silica nanoparticles and a natural product approach

    Science.gov (United States)

    White-Schenk, Désirée.; Shi, Riyi; Leary, James F.

    2014-03-01

    Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDAapproved hypotensive drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica particles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The current work exposes the potential of using silica nanoparticles as a delivery vehicle and EGCG's antioxidant capabilities in B35 neuroblastoma cells exposed to acrolein. We also measure nanotoxicity to individual rat neurons using high-throughput image scanning cytometry.

  2. Biocontrol of tomato wilt disease by Bacillus subtilis isolates from natural environments depends on conserved genes mediating biofilm formation

    Science.gov (United States)

    Liu, Hongxia; Kolter, Roberto; Losick, Richard; Guo, Jian-hua

    2014-01-01

    Summary Bacillus subtilis and other Bacilli have long been used as biological control agents against plant bacterial diseases but the mechanisms by which the bacteria confer protection are not well understood. Our goal in this study was to isolate strains of B. subtilis that exhibit high levels of biocontrol efficacy from natural environments and to investigate the mechanisms by which these strains confer plant protection. We screened a total of sixty isolates collected from various locations across China and obtained six strains that exhibited above 50% biocontrol efficacy on tomato plants against the plant pathogen Ralstonia solanacearum under greenhouse conditions. These wild strains were able to form robust biofilms both in defined medium and on tomato plant roots and exhibited strong antagonistic activities against various plant pathogens in plate assays. We show that plant protection by those strains depended on widely conserved genes required for biofilm formation, including regulatory genes and genes for matrix production. We provide evidence suggesting that matrix production is critical for bacterial colonization on plant root surfaces. Finally, we have established a model system for studies of B. subtilis-tomato plant interactions in protection against a plant pathogen. PMID:22934631

  3. High-level expression of an antimicrobial peptide histonin as a natural form by multimerization and furin-mediated cleavage.

    Science.gov (United States)

    Kim, Jung Min; Jang, Su A; Yu, Byung Jo; Sung, Bong Hyun; Cho, Ju Hyun; Kim, Sun Chang

    2008-02-01

    Direct expression of an antimicrobial peptide (AMP) in Escherichia coli causes several problems such as the toxicity of AMP to the host cell, its susceptibility to proteolytic degradation, and decreased antimicrobial activity due to the additional residue(s) introduced after cleavage of AMPs from fusion partners. To overcome these problems and produce a large quantity of a potent AMP histonin (RAGLQFPVGKLLKKLLKRLKR) in E. coli, an efficient expression system was developed, in which the toxicity of histonin was neutralized by a fusion partner F4 (a truncated fragment of PurF protein) and the productivity was increased by a multimeric expression of a histonin gene. The expression level of the fusion proteins reached a maximum with a 12-mer of a histonin gene. In addition, because of the RLKR residues present at the C terminus of histonin, furin cleavage of the multimeric histonin expressed produces an intact, natural histonin. The AMP activity of the histonin produced in E. coli was identical to that of a synthetic histonin. With our expression system, 167 mg of histonin was obtained from 1 l of E. coli culture. These results may lead to a cost-effective solution for the mass production of AMPs that are toxic to a host.

  4. The activating receptor NKG2D of natural killer cells promotes resistance against enterovirus-mediated inflammatory cardiomyopathy.

    Science.gov (United States)

    Klingel, Karin; Fabritius, Cornelia; Sauter, Martina; Göldner, Katrin; Stauch, Diana; Kandolf, Reinhard; Ettischer, Nicole; Gahlen, Sabine; Schönberger, Tanja; Ebner, Susanne; Makrigiannis, Andrew P; Bélanger, Simon; Diefenbach, Andreas; Polić, Bojan; Pratschke, Johann; Kotsch, Katja

    2014-10-01

    In enterovirus-induced cardiomyopathy, information regarding the detailed impact of natural killer (NK) cells on the outcome of the disease is limited. We therefore hypothesized that NK cells and certain NK cell receptors determine the different outcome of coxsackievirus B3 (CVB3) myocarditis. Here, we demonstrate in murine models that resistance to chronic CVB3 myocarditis in immunocompetent C57BL/6 mice is characterized by significantly more mature CD11b(high) NK cells, the presence of NKG2D on NK cells, and enhanced NKG2D-dependent cytotoxicity compared to CVB3-susceptible A.BY/SnJ mice. The highly protective role of NKG2D in myocarditis was further proven by in vivo neutralization of NKG2D as well as in NKG2D-deficient mice but was shown to be independent of CD8(+) T-cell-dependent immunity. Moreover, the adoptive transfer of immunocompetent C57BL/6 NK cells pre- (day -1) as well as post-infectionem (day +2) displayed the potential to prevent permissive A.BY/SnJ mice from a progressive outcome of CVB3 myocarditis reflected by significantly improved cardiopathology and heart function. Altogether, our results provide firm evidence for a protective role of NKG2D-activated NK cells in CVB3 myocarditis leading to an effective virus clearance, thus offering novel therapeutic options in the treatment of virus-induced myocarditis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. Enhanced viral production and virus-mediated mortality of bacterioplankton in a natural iron-fertilized bloom event above the Kerguelen Plateau

    Science.gov (United States)

    Malits, A.; Christaki, U.; Obernosterer, I.; Weinbauer, M. G.

    2014-12-01

    Above the Kerguelen Plateau in the Southern Ocean natural iron fertilization sustains a large phytoplankton bloom over 3 months during austral summer. During the KEOPS1 project (KErguelen Ocean and Plateau compared Study1) we sampled this phytoplankton bloom during its declining phase along with the surrounding high-nutrient-low-chlorophyll (HNLC) waters to study the effect of natural iron fertilization on the role of viruses in the microbial food web. Bacterial and viral abundances were 1.7 and 2.1 times, respectively, higher within the bloom than in HNLC waters. Viral production and virus-mediated mortality of bacterioplankton were 4.1 and 4.9 times, respectively, higher in the bloom, while the fraction of infected cells (FIC) and the fraction of lysogenic cells (FLC) showed no significant differences between environments. The present study suggests viruses to be more important for bacterial mortality within the bloom and dominate over grazing of heterotrophic nanoflagellates (HNFs) during the late bloom phase. As a consequence, at least at a late bloom stage, viral lysis shunts part of the photosynthetically fixed carbon in iron-fertilized regions into the dissolved organic matter (DOM) pool with potentially less particulate organic carbon transferred to larger members of the food web or exported.

  6. How Elementary Teachers' Beliefs About the Nature of Science Mediate Implementing Prescribed Science Curricula in Their Classrooms

    Science.gov (United States)

    Giglio, Kathleen Rose Fitzgerald

    This is an in depth study of two elementary school teachers, who are generalists because they teach multiple subjects to their classes, in addition to science, respectively in grade 3 and grade 6. The teachers taught and their students learned using a contemporary understanding of the nature of science (NOS), which they learned by actually doing science investigations, rather than being explicitly told about NOS (contrary to what some scholars claim). Neither teacher completed any formal/informal science training/experiences, especially connected to the construct NOS. Even though the teachers did not explicitly reference NOS in the classroom, their teaching about NOS was made possible through their implementation of the FOSS ( Full Option Science System) curriculum. Although their students enthusiastically demonstrated competence in both science process and content, as prescribed by the FOSS curriculum, the teachers' felt undermined by the state mandated assessments and the inclusion of student performance as a criterion for the state teacher evaluation system. This research was designed to answer the following questions: (1) What are elementary teachers' conceptions about NOS? (2) How are the teachers' NOS views manifested in their implementation of the FOSS program and their choices of instructional methods/materials? (3) What factors may have enhanced or hindered how the teachers sustained their NOS conceptions as they implemented the FOSS program? To explicate the relationship between teachers' views of NOS and the extent to which constructivist practices were employed in their science instruction, a multiple research methodology using grounded theory as the foundation and employing both quantitative and qualitative measures, was needed. Sources of quantitative data were written survey results using the Student Understanding of Science and Scientific Inquiry Questionnaire (SUSSI; Liang et al., 2008) Likert scale responses and constructed responses. Face

  7. Language, knowledge, and mystical mediation: magic, clergy and intervention on the nature in the quotidian and representations in Medieval West - doi: 10.4025/actascieduc.v34i1.15881

    OpenAIRE

    Rita de Cássia Mendes Pereira

    2012-01-01

    The Reading of documents of ecclesiastical source produced during Middle Ages provides the very clear percept of the presence of various categories of mediators between the natural world and mystical forces, in the daily routine of the western men. On the one hand, there were the wizards, expert supposedly endowed with special knowledge, who used as a resource various forms of exercise of divinatory arts and techniques of manipulation of elements of nature. During Middle Ages the ecclesiastic...

  8. Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function.

    Science.gov (United States)

    D'Ursi, Pasqualina; Orro, Alessandro; Morra, Giulia; Moscatelli, Marco; Trombetti, Gabriele; Milanesi, Luciano; Rovida, Ermanna

    2015-01-01

    Activated Protein C (APC) is a multifunctional serine protease, primarily known for its anticoagulant function in the coagulation system. Several studies have already elucidated its role in counteracting apoptosis and inflammation in cells, while significant effort is still ongoing for defining its involvement in sepsis. Earlier literature has shown that the antiseptic function of APC is mediated by its binding to leukocyte integrins, which is due to the presence of the integrin binding motif Arg-Gly-Asp at the N-terminus of the APC catalytic chain. Many natural mutants have been identified in patients with Protein C deficiency diagnosis including a variant of specificity pocket (Gly216Asp). In this work, we present a molecular model of the complex of APC with αVβ3 integrin obtained by protein-protein docking approach. A computational analysis of this variant is hereby presented, based on molecular dynamics and docking simulations, aiming at investigating the effects of the Gly216Asp mutation on the protein conformation and inferring its functional implications. Our study shows that such mutation is likely to impair the protease activity while preserving the overall protein fold. Moreover, superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding. Therapeutic applications could result in this APC mutant which retains antiseptic function without anticoagulant side effects.

  9. Northernmost record of the pantropical portunid crab Cronius ruber in the eastern Atlantic (Canary Islands: natural range extension or human-mediated introduction?

    Directory of Open Access Journals (Sweden)

    José A. González

    2017-03-01

    Full Text Available The pantropical crab Cronius ruber (Lamarck, 1818 (Brachyura: Portunidae is recorded for the first time from the Canary Islands. Previously known from off Cape Verde Islands and Senegal, this is the northernmost record of the species in the eastern Atlantic Ocean. Crabs have been caught by means of a collecting small trap for sampling in shallow waters, and then identified by both morphological characters and DNA barcoding (16S. Cytochrome c oxidase I partial sequence has been obtained for this species for the first time. This relatively large and very aggressive crab species seems to be rapidly occupying both hard substrates (sublittoral caves and soft substrates (sand with seagrass meadow adjacent to shallow rocky bottoms, at depths between 2 and 10 m, in the warm southern waters of Gran Canaria Island. The reasons for this species’ occurrence are discussed herein. Among them, natural range extension may be a consequence of tropicalization in the eastern Atlantic. Also, a human-mediated introduction could be based on the heavy traffic of ships (ballast waters or oil platforms arriving at the Canary Islands from African countries and from Brazil in the last decade.

  10. Effect of irradiation-induced intercellular adhesion molecule-1 expression on natural killer cell-mediated cytotoxicity toward human cancer cells.

    Science.gov (United States)

    Jeong, Jae-Uk; Uong, Tung Nguyen Thanh; Chung, Woong-Ki; Nam, Taek-Keun; Ahn, Sung-Ja; Song, Ju-Young; Kim, Sang-Ki; Shin, Dong-Jun; Cho, Eugene; Kim, Kyoung Won; Cho, Duck; Yoon, Mee Sun

    2018-03-20

    Irradiation enhances the adhesion between natural killer (NK) cells and target cells by up-regulating intercellular adhesion molecule-1 (ICAM-1) on target cells. Therefore, we investigated the effect of irradiation-induced ICAM-1 expression on human cancer cells on NK cell-mediated cytotoxicity. Expression levels of ICAM-1 on the target cell surface before and after irradiation of six human cancer cell lines (HL60, SKBR-3, T47D, HCT-116, U937 and U251) were analyzed by flow cytometry. Ex vivo expansion of NK cells from human peripheral blood mononuclear cells was performed by co-culture with irradiated K562 cells. The related adhesion molecule lymphocyte function-associated antigen 1 (LFA-1) on NK cells was analyzed by flow cytometry. An enzyme-linked immunosorbent assay was used to detect interferon-γ (IFN-γ), and WST-8 assays were performed to check NK cell cytotoxicity. Finally, blocking assays were performed using monoclonal antibodies against ICAM-1 or LFA-1. LFA-1 expression increased on NK cells after expansion (P cytotoxicity increased after irradiation of HL60 (P cytotoxicity against irradiated SKBR-3 (P cytotoxicity against irradiated HL60 (P cytotoxicity. Therefore, irradiation combined with NK cell therapy may improve the antitumor effects of NK cells. Copyright © 2018. Published by Elsevier Inc.

  11. Search for scalar top quark pair production in natural gauge mediated supersymmetry models with the ATLAS detector in pp collisions at $\\sqrt{s}$ = 7 TeV

    CERN Document Server

    Aad, Georges; Abdallah, Jalal; Abdel Khalek, Samah; Abdelalim, Ahmed Ali; Abdinov, Ovsat; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Acerbi, Emilio; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Addy, Tetteh; Adelman, Jahred; Adomeit, Stefanie; Adragna, Paolo; Adye, Tim; Aefsky, Scott; Aguilar-Saavedra, Juan Antonio; Aharrouche, Mohamed; Ahlen, Steven; Ahles, Florian; Ahmad, Ashfaq; Ahsan, Mahsana; Aielli, Giulio; Akdogan, Taylan; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Akiyama, Kunihiro; Alam, Mohammad; Alam, Muhammad Aftab; Albert, Justin; Albrand, Solveig; Aleksa, Martin; Aleksandrov, Igor; Alessandria, Franco; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Aliev, Malik; Alimonti, Gianluca; Alison, John; Allbrooke, Benedict; Allport, Phillip; Allwood-Spiers, Sarah; Almond, John; Aloisio, Alberto; Alon, Raz; Alonso, Alejandro; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amako, Katsuya; Amelung, Christoph; Ammosov, Vladimir; Amorim, Antonio; Amorós, Gabriel; Amram, Nir; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Anduaga, Xabier; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonaki, Ariadni; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoun, Sahar; Aperio Bella, Ludovica; Apolle, Rudi; Arabidze, Giorgi; Aracena, Ignacio; Arai, Yasuo; Arce, Ayana; Arfaoui, Samir; Arguin, Jean-Francois; Arik, Engin; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnault, Christian; Artamonov, Andrei; Artoni, Giacomo; Arutinov, David; Asai, Shoji; Asfandiyarov, Ruslan; Ask, Stefan; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astbury, Alan; Aubert, Bernard; Auge, Etienne; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Avramidou, Rachel Maria; Axen, David; Azuelos, Georges; Azuma, Yuya; Baak, Max; Baccaglioni, Giuseppe; Bacci, Cesare; Bach, Andre; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Badescu, Elisabeta; Bagnaia, Paolo; Bahinipati, Seema; Bai, Yu; Bailey, David; Bain, Travis; Baines, John; Baker, Oliver Keith; Baker, Mark; Baker, Sarah; Banas, Elzbieta; Banerjee, Piyali; Banerjee, Swagato; Banfi, Danilo; Bangert, Andrea Michelle; Bansal, Vikas; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barbaro Galtieri, Angela; Barber, Tom; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Bardin, Dmitri; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnett, Bruce; Barnett, Michael; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Barrillon, Pierre; Bartoldus, Rainer; Barton, Adam Edward; Bartsch, Valeria; Bates, Richard; Batkova, Lucia; Batley, Richard; Battaglia, Andreas; Battistin, Michele; Bauer, Florian; Bawa, Harinder Singh; Beale, Steven; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Sebastian; Beckingham, Matthew; Becks, Karl-Heinz; Beddall, Andrew; Beddall, Ayda; Bedikian, Sourpouhi; Bednyakov, Vadim; Bee, Christopher; Begel, Michael; Behar Harpaz, Silvia; Behera, Prafulla; Beimforde, Michael; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellina, Francesco; Bellomo, Massimiliano; Belloni, Alberto; Beloborodova, Olga; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Benoit, Mathieu; Bensinger, James; Benslama, Kamal; Bentvelsen, Stan; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Berglund, Elina; Beringer, Jürg; Bernat, Pauline; Bernhard, Ralf; Bernius, Catrin; Berry, Tracey; Bertella, Claudia; Bertin, Antonio; Bertolucci, Federico; Besana, Maria Ilaria; Besson, Nathalie; Bethke, Siegfried; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Bierwagen, Katharina; Biesiada, Jed; Biglietti, Michela; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Biscarat, Catherine; Bitenc, Urban; Black, Kevin; Blair, Robert; Blanchard, Jean-Baptiste; Blanchot, Georges; Blazek, Tomas; Blocker, Craig; Blocki, Jacek; Blondel, Alain; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Boddy, Christopher Richard; Boehler, Michael; Boek, Jennifer; Boelaert, Nele; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bogouch, Andrei; Bohm, Christian; Bohm, Jan; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Bolnet, Nayanka Myriam; Bomben, Marco; Bona, Marcella; Bondioli, Mario; Boonekamp, Maarten; Booth, Chris; Bordoni, Stefania; Borer, Claudia; Borisov, Anatoly; Borissov, Guennadi; Borjanovic, Iris; Borri, Marcello; Borroni, Sara; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boterenbrood, Hendrik; Botterill, David; Bouchami, Jihene; Boudreau, Joseph; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozhko, Nikolay; Bozovic-Jelisavcic, Ivanka; Bracinik, Juraj; Branchini, Paolo; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brelier, Bertrand; Bremer, Johan; Brendlinger, Kurt; Brenner, Richard; Bressler, Shikma; Britton, Dave; Brochu, Frederic; Brock, Ian; Brock, Raymond; Brodet, Eyal; Broggi, Francesco; Bromberg, Carl; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, William; Brown, Gareth; Brown, Heather; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Brunet, Sylvie; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Buanes, Trygve; Buat, Quentin; Bucci, Francesca; Buchanan, James; Buchholz, Peter; Buckingham, Ryan; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Budick, Burton; Büscher, Volker; Bugge, Lars; Bulekov, Oleg; Bundock, Aaron Colin; Bunse, Moritz; Buran, Torleiv; Burckhart, Helfried; Burdin, Sergey; Burgess, Thomas; Burke, Stephen; Busato, Emmanuel; Bussey, Peter; Buszello, Claus-Peter; Butler, Bart; Butler, John; Buttar, Craig; Butterworth, Jonathan; Buttinger, William; Cabrera Urbán, Susana; Caforio, Davide; Cakir, Orhan; Calafiura, Paolo; Calderini, Giovanni; Calfayan, Philippe; Calkins, Robert; Caloba, Luiz; Caloi, Rita; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarri, Paolo; Cameron, David; Caminada, Lea Michaela; Campana, Simone; Campanelli, Mario; Canale, Vincenzo; Canelli, Florencia; Canepa, Anadi; Cantero, Josu; Capasso, Luciano; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capriotti, Daniele; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Bryan; Caron, Sascha; Carquin, Edson; Carrillo Montoya, German D; Carter, Antony; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Cascella, Michele; Caso, Carlo; Castaneda Hernandez, Alfredo Martin; Castaneda-Miranda, Elizabeth; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Cataldi, Gabriella; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Cattani, Giordano; Caughron, Seth; Cauz, Diego; Cavalleri, Pietro; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chan, Kevin; Chapleau, Bertrand; Chapman, John Derek; Chapman, John Wehrley; Chareyre, Eve; Charlton, Dave; Chavda, Vikash; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Shenjian; Chen, Xin; Cheplakov, Alexander; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Cheung, Sing-Leung; Chevalier, Laurent; Chiefari, Giovanni; Chikovani, Leila; Childers, John Taylor; Chilingarov, Alexandre; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chizhov, Mihail; Choudalakis, Georgios; Chouridou, Sofia; Christidi, Illectra-Athanasia; Christov, Asen; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Ciapetti, Guido; Ciftci, Abbas Kenan; Ciftci, Rena; Cinca, Diane; Cindro, Vladimir; Ciocca, Claudia; Ciocio, Alessandra; Cirilli, Manuela; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Philip James; Cleland, Bill; Clemens, Jean-Claude; Clement, Benoit; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coe, Paul; Cogan, Joshua Godfrey; Coggeshall, James; Cogneras, Eric; Colas, Jacques; Colijn, Auke-Pieter; Collins, Neil; Collins-Tooth, Christopher; Collot, Johann; Colon, German; Conde Muiño, Patricia; Coniavitis, Elias; Conidi, Maria Chiara; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Costin, Tudor; Côté, David; Courneyea, Lorraine; Cowan, Glen; Cowden, Christopher; Cox, Brian; Cranmer, Kyle; Crescioli, Francesco; Cristinziani, Markus; Crosetti, Giovanni; Crupi, Roberto; Crépé-Renaudin, Sabine; Cuciuc, Constantin-Mihai; Cuenca Almenar, Cristóbal; Cuhadar Donszelmann, Tulay; Curatolo, Maria; Curtis, Chris; Cuthbert, Cameron; Cwetanski, Peter; Czirr, Hendrik; Czodrowski, Patrick; Czyczula, Zofia; D'Auria, Saverio; D'Onofrio, Monica; D'Orazio, Alessia; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dallapiccola, Carlo; Dam, Mogens; Dameri, Mauro; Damiani, Daniel; Danielsson, Hans Olof; Dao, Valerio; Darbo, Giovanni; Darlea, Georgiana Lavinia; Davey, Will; Davidek, Tomas; Davidson, Nadia; Davidson, Ruth; Davies, Eleanor; Davies, Merlin; Davison, Adam; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; de Graat, Julien; De Groot, Nicolo; de Jong, Paul; De La Taille, Christophe; De la Torre, Hector; De Lorenzi, Francesco; De Lotto, Barbara; de Mora, Lee; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; De Zorzi, Guido; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Degenhardt, James; Del Papa, Carlo; Del Peso, Jose; Del Prete, Tarcisio; Delemontex, Thomas; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; Demers, Sarah; Demichev, Mikhail; Demirkoz, Bilge; Deng, Jianrong; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Devetak, Erik; Deviveiros, Pier-Olivier; Dewhurst, Alastair; DeWilde, Burton; Dhaliwal, Saminder; Dhullipudi, Ramasudhakar; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Luise, Silvestro; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Diaz, Marco Aurelio; Diblen, Faruk; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dindar Yagci, Kamile; Dingfelder, Jochen; Dionisi, Carlo; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Barros do Vale, Maria Aline; Do Valle Wemans, André; Doan, Thi Kieu Oanh; Dobbs, Matt; Dobinson, Robert; Dobos, Daniel; Dobson, Ellie; Dodd, Jeremy; Doglioni, Caterina; Doherty, Tom; Doi, Yoshikuni; Dolejsi, Jiri; Dolenc, Irena; Dolezal, Zdenek; Dolgoshein, Boris; Dohmae, Takeshi; Donadelli, Marisilvia; Donega, Mauro; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dos Anjos, Andre; Dotti, Andrea; Dova, Maria-Teresa; Doxiadis, Alexander; Doyle, Tony; Dris, Manolis; Dubbert, Jörg; Dube, Sourabh; Duchovni, Ehud; Duckeck, Guenter; Dudarev, Alexey; Dudziak, Fanny; Dührssen, Michael; Duerdoth, Ian; Duflot, Laurent; Dufour, Marc-Andre; Dunford, Monica; Duran Yildiz, Hatice; Duxfield, Robert; Dwuznik, Michal; Dydak, Friedrich; Düren, Michael; Ebke, Johannes; Eckweiler, Sebastian; Edmonds, Keith; Edwards, Clive; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Eisenhandler, Eric; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Ellis, Katherine; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Engelmann, Roderich; Engl, Albert; Epp, Brigitte; Eppig, Andrew; Erdmann, Johannes; Ereditato, Antonio; Eriksson, Daniel; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Deborah; Errede, Steven; Ertel, Eugen; Escalier, Marc; Escobar, Carlos; Espinal Curull, Xavier; Esposito, Bellisario; Etienne, Francois; Etienvre, Anne-Isabelle; Etzion, Erez; Evangelakou, Despoina; Evans, Hal; Fabbri, Laura; Fabre, Caroline; Fakhrutdinov, Rinat; Falciano, Speranza; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farley, Jason; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassnacht, Patrick; Fassouliotis, Dimitrios; Fatholahzadeh, Baharak; Favareto, Andrea; Fayard, Louis; Fazio, Salvatore; Febbraro, Renato; Federic, Pavol; Fedin, Oleg; Fedorko, Woiciech; Fehling-Kaschek, Mirjam; Feligioni, Lorenzo; Fellmann, Denis; Feng, Cunfeng; Feng, Eric; Fenyuk, Alexander; Ferencei, Jozef; Fernando, Waruna; Ferrag, Samir; Ferrando, James; Ferrara, Valentina; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filthaut, Frank; Fincke-Keeler, Margret; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Gordon; Fisher, Matthew; Flechl, Martin; Fleck, Ivor; Fleckner, Johanna; Fleischmann, Philipp; Fleischmann, Sebastian; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Fonseca Martin, Teresa; Forbush, David Alan; Formica, Andrea; Forti, Alessandra; Fortin, Dominique; Fournier, Daniel; Fox, Harald; Francavilla, Paolo; Franchino, Silvia; Francis, David; Frank, Tal; Franklin, Melissa; Franz, Sebastien; Fraternali, Marco; Fratina, Sasa; French, Sky; Friedrich, Conrad; Friedrich, Felix; Froeschl, Robert; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gadfort, Thomas; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Gallas, Elizabeth; Gallo, Valentina Santina; Gallop, Bruce; Gallus, Petr; Gan, KK; Gao, Yongsheng; Gaponenko, Andrei; Garberson, Ford; Garcia-Sciveres, Maurice; García, Carmen; García Navarro, José Enrique; Gardner, Robert; Garelli, Nicoletta; Garitaonandia, Hegoi; Garonne, Vincent; Garvey, John; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gellerstedt, Karl; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerlach, Peter; Gershon, Avi; Geweniger, Christoph; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giakoumopoulou, Victoria; Giangiobbe, Vincent; Gianotti, Fabiola; Gibbard, Bruce; Gibson, Adam; Gibson, Stephen; Gillberg, Dag; Gillman, Tony; Gingrich, Douglas; Ginzburg, Jonatan; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Francesco Michelangelo; Giovannini, Paola; Giraud, Pierre-Francois; Giugni, Danilo; Giunta, Michele; Giusti, Paolo; Gjelsten, Børge Kile; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glazov, Alexandre; Glitza, Karl-Walter; Glonti, George; Goddard, Jack Robert; Godfrey, Jennifer; Godlewski, Jan; Goebel, Martin; Göpfert, Thomas; Goeringer, Christian; Gössling, Claus; Goldfarb, Steven; Golling, Tobias; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; Gonzalez, Saul; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez Silva, Laura; Gonzalez-Sevilla, Sergio; Goodson, Jeremiah Jet; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorfine, Grant; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Gosdzik, Bjoern; Goshaw, Alfred; Gosselink, Martijn; Gostkin, Mikhail Ivanovitch; Gough Eschrich, Ivo; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Gozpinar, Serdar; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Grancagnolo, Francesco; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Grau, Nathan; Gray, Heather; Gray, Julia Ann; Graziani, Enrico; Grebenyuk, Oleg; Greenshaw, Timothy; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grigalashvili, Nugzar; Grillo, Alexander; Grinstein, Sebastian; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Gross, Eilam; Grosse-Knetter, Joern; Groth-Jensen, Jacob; Grybel, Kai; Guest, Daniel; Guicheney, Christophe; Guida, Angelo; Guindon, Stefan; Guler, Hulya; Gunther, Jaroslav; Guo, Bin; Guo, Jun; Gushchin, Vladimir; Gutierrez, Phillip; Guttman, Nir; Gutzwiller, Olivier; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haas, Stefan; Haber, Carl; Hadavand, Haleh Khani; Hadley, David; Haefner, Petra; Hahn, Ferdinand; Haider, Stefan; Hajduk, Zbigniew; Hakobyan, Hrachya; Hall, David; Haller, Johannes; Hamacher, Klaus; Hamal, Petr; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Handel, Carsten; Hanke, Paul; Hansen, John Renner; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hansson, Per; Hara, Kazuhiko; Hare, Gabriel; Harenberg, Torsten; Harkusha, Siarhei; Harper, Devin; Harrington, Robert; Harris, Orin; Harrison, Karl; Hartert, Jochen; Hartjes, Fred; Haruyama, Tomiyoshi; Harvey, Alex; Hasegawa, Satoshi; Hasegawa, Yoji; Hassani, Samira; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hawkins, Donovan; Hayakawa, Takashi; Hayashi, Takayasu; Hayden, Daniel; Hayward, Helen; Haywood, Stephen; He, Mao; Head, Simon; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heinemann, Beate; Heisterkamp, Simon; Helary, Louis; Heller, Claudio; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, Robert; Henke, Michael; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Henry-Couannier, Frédéric; Hensel, Carsten; Henß, Tobias; Medina Hernandez, Carlos; Hernández Jiménez, Yesenia; Herrberg, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Higón-Rodriguez, Emilio; Hill, John; Hiller, Karl Heinz; Hillert, Sonja; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirsch, Florian; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoffman, Julia; Hoffmann, Dirk; Hohlfeld, Marc; Holder, Martin; Holmgren, Sven-Olof; Holy, Tomas; Holzbauer, Jenny; Hong, Tae Min; Hooft van Huysduynen, Loek; Horn, Claus; Horner, Stephan; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howarth, James; Hristova, Ivana; Hrivnac, Julius; Hruska, Ivan; Hryn'ova, Tetiana; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huettmann, Antje; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hurwitz, Martina; Husemann, Ulrich; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibbotson, Michael; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idarraga, John; Iengo, Paolo; Igonkina, Olga; Ikegami, Yoichi; Ikeno, Masahiro; Iliadis, Dimitrios; Ilic, Nikolina; Imori, Masatoshi; Ince, Tayfun; Inigo-Golfin, Joaquin; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishikawa, Akimasa; Ishino, Masaya; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Ivashin, Anton; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, John; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakubek, Jan; Jana, Dilip; Jansen, Eric; Jansen, Hendrik; Jantsch, Andreas; Janus, Michel; Jarlskog, Göran; Jeanty, Laura; Jen-La Plante, Imai; Jenni, Peter; Jeremie, Andrea; Jež, Pavel; Jézéquel, Stéphane; Jha, Manoj Kumar; Ji, Haoshuang; Ji, Weina; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinnouchi, Osamu; Joergensen, Morten Dam; Joffe, David; Johansen, Lars; Johansen, Marianne; Johansson, Erik; Johansson, Per; Johnert, Sebastian; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Joram, Christian; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Jovin, Tatjana; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Juranek, Vojtech; Jussel, Patrick; Juste Rozas, Aurelio; Kabana, Sonja; Kaci, Mohammed; Kaczmarska, Anna; Kadlecik, Peter; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kalinin, Sergey; Kalinovskaya, Lidia; Kama, Sami; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kanno, Takayuki; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kaplon, Jan; Kar, Deepak; Karagounis, Michael; Karnevskiy, Mikhail; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Mayuko; Kataoka, Yousuke; Katsoufis, Elias; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kayl, Manuel; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Kekelidze, George; Keller, John; Kennedy, John; Kenyon, Mike; Kepka, Oldrich; Kerschen, Nicolas; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharchenko, Dmitri; Khodinov, Alexander; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khoroshilov, Andrey; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hyeon Jin; Kim, Min Suk; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kittelmann, Thomas; Kiver, Andrey; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klemetti, Miika; Klier, Amit; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klinkby, Esben; Klioutchnikova, Tatiana; Klok, Peter; Klous, Sander; Kluge, Eike-Erik; Kluge, Thomas; Kluit, Peter; Kluth, Stefan; Knecht, Neil; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Ko, Byeong Rok; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Köneke, Karsten; König, Adriaan; Koenig, Sebastian; Köpke, Lutz; Koetsveld, Folkert; Koevesarki, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohn, Fabian; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolachev, Guennady; Kolanoski, Hermann; Kolesnikov, Vladimir; Koletsou, Iro; Koll, James; Kollefrath, Michael; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kono, Takanori; Kononov, Anatoly; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kootz, Andreas; Koperny, Stefan; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Sergey; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kral, Vlastimil; Kramarenko, Viktor; Kramberger, Gregor; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, James; Kraus, Jana; Krejci, Frantisek; Kretzschmar, Jan; Krieger, Nina; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kruth, Andre; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Thorsten; Kuhn, Dietmar; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kummer, Christian; Kuna, Marine; Kunkle, Joshua; Kupco, Alexander; Kurashige, Hisaya; Kurata, Masakazu; Kurochkin, Yurii; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwee, Regina; La Rosa, Alessandro; La Rotonda, Laura; Labarga, Luis; Labbe, Julien; Lablak, Said; Lacasta, Carlos; Lacava, Francesco; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laisne, Emmanuel; Lamanna, Massimo; Lambourne, Luke; Lampen, Caleb; Lampl, Walter; Lancon, Eric; Landgraf, Ulrich; Landon, Murrough; Lane, Jenna; Lange, Clemens; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Larner, Aimee; Lassnig, Mario; Laurelli, Paolo; Lavorini, Vincenzo; Lavrijsen, Wim; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Maner, Christophe; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Michel; Legendre, Marie; LeGeyt, Benjamin; Legger, Federica; Leggett, Charles; Lehmacher, Marc; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Lendermann, Victor; Leney, Katharine; Lenz, Tatiana; Lenzen, Georg; Lenzi, Bruno; Leonhardt, Kathrin; Leontsinis, Stefanos; Lepold, Florian; Leroy, Claude; Lessard, Jean-Raphael; Lester, Christopher; Lester, Christopher Michael; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bo; Li, Haifeng; Li, Shu; Li, Xuefei; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lichtnecker, Markus; Lie, Ki; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Limper, Maaike; Lin, Simon; Linde, Frank; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Chuanlei; Liu, Dong; Liu, Hao; Liu, Jianbei; Liu, Minghui; Liu, Yanwen; Livan, Michele; Livermore, Sarah; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loginov, Andrey; Loh, Chang Wei; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Lombardo, Vincenzo Paolo; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lo Sterzo, Francesco; Losty, Michael; Lou, Xinchou; Lounis, Abdenour; Loureiro, Karina; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Ludwig, Andreas; Ludwig, Dörthe; Ludwig, Inga; Ludwig, Jens; Luehring, Frederick; Luijckx, Guy; Lukas, Wolfgang; Lumb, Debra; Luminari, Lamberto; Lund, Esben; Lund-Jensen, Bengt; Lundberg, Björn; Lundberg, Johan; Lundquist, Johan; Lungwitz, Matthias; Lynn, David; Lytken, Else; Ma, Hong; Ma, Lian Liang; Macana Goia, Jorge Andres; Maccarrone, Giovanni; Macchiolo, Anna; Maček, Boštjan; Machado Miguens, Joana; Mackeprang, Rasmus; Madaras, Ronald; Mader, Wolfgang; Maenner, Reinhard; Maeno, Tadashi; Mättig, Peter; Mättig, Stefan; Magnoni, Luca; Magradze, Erekle; Mahboubi, Kambiz; Mahmoud, Sara; Mahout, Gilles; Maiani, Camilla; Maidantchik, Carmen; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Malecki, Piotr; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mameghani, Raphael; Mamuzic, Judita; Manabe, Atsushi; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Mangeard, Pierre-Simon; Manhaes de Andrade Filho, Luciano; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mapelli, Alessandro; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchese, Fabrizio; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marroquim, Fernando; Marshall, Zach; Martens, Kalen; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian Thomas; Martin, Jean-Pierre; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martin-Haugh, Stewart; Martinez, Mario; Martinez Outschoorn, Verena; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massaro, Graziano; Massol, Nicolas; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Matricon, Pierre; Matsunaga, Hiroyuki; Matsushita, Takashi; Mattravers, Carly; Maurer, Julien; Maxfield, Stephen; Mayne, Anna; Mazini, Rachid; Mazur, Michael; Mazzaferro, Luca; Mazzanti, Marcello; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; McGlone, Helen; Mchedlidze, Gvantsa; Mclaughlan, Tom; McMahon, Steve; McPherson, Robert; Meade, Andrew; Mechnich, Joerg; Mechtel, Markus; Medinnis, Mike; Meera-Lebbai, Razzak; Meguro, Tatsuma; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mendoza Navas, Luis; Meng, Zhaoxia; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer, Joerg; Meyer, Thomas Christian; Meyer, W Thomas; Miao, Jiayuan; Michal, Sebastien; Micu, Liliana; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Miller, David; Miller, Robert; Mills, Bill; Mills, Corrinne; Milov, Alexander; Milstead, David; Milstein, Dmitry; Minaenko, Andrey; Miñano Moya, Mercedes; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Mitrevski, Jovan; Mitsou, Vasiliki A; Mitsui, Shingo; Miyagawa, Paul; Miyazaki, Kazuki; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mockett, Paul; Moed, Shulamit; Moeller, Victoria; Mönig, Klaus; Möser, Nicolas; Mohapatra, Soumya; Mohr, Wolfgang; Moles-Valls, Regina; Molina-Perez, Jorge; Monk, James; Monnier, Emmanuel; Montesano, Simone; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Moorhead, Gareth; Mora Herrera, Clemencia; Moraes, Arthur; Morange, Nicolas; Morel, Julien; Morello, Gianfranco; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morin, Jerome; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Mueller, Felix; Mueller, James; Mueller, Klemens; Müller, Thomas; Mueller, Timo; Muenstermann, Daniel; Munwes, Yonathan; Murray, Bill; Mussche, Ido; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nadal, Jordi; Nagai, Koichi; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Nanava, Gizo; Napier, Austin; Narayan, Rohin; Nash, Michael; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negri, Guido; Nektarijevic, Snezana; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neusiedl, Andrea; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen Thi Hong, Van; Nickerson, Richard; Nicolaidou, Rosy; Nicolas, Ludovic; Nicquevert, Bertrand; Niedercorn, Francois; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsen, Henrik; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nishiyama, Tomonori; Nisius, Richard; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Nordberg, Markus; Norton, Peter; Novakova, Jana; Nozaki, Mitsuaki; Nozka, Libor; Nugent, Ian Michael; Nuncio-Quiroz, Adriana-Elizabeth; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; O'Brien, Brendan Joseph; O'Neale, Steve; O'Neil, Dugan; O'Shea, Val; Oakes, Louise Beth; Oakham, Gerald; Oberlack, Horst; Ocariz, Jose; Ochi, Atsuhiko; Oda, Susumu; Odaka, Shigeru; Odier, Jerome; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohshima, Takayoshi; Okada, Shogo; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira, Miguel Alfonso; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olivito, Dominick; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orlov, Iliya; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Osuna, Carlos; Otero y Garzon, Gustavo; Ottersbach, John; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Simon; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganis, Efstathios; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Paleari, Chiara; Palestini, Sandro; Pallin, Dominique; Palma, Alberto; Palmer, Jody; Pan, Yibin; Panagiotopoulou, Evgenia; Panikashvili, Natalia; Panitkin, Sergey; Pantea, Dan; Papadelis, Aras; Papadopoulou, Theodora; Paramonov, Alexander; Paredes Hernandez, Daniela; Park, Woochun; Parker, Andy; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pashapour, Shabnaz; Pasqualucci, Enrico; Passaggio, Stefano; Passeri, Antonio; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Patricelli, Sergio; Pauly, Thilo; Pecsy, Martin; Pedraza Morales, Maria Isabel; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penson, Alexander; Penwell, John; Perantoni, Marcelo; Perez, Kerstin; Perez Cavalcanti, Tiago; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perez Reale, Valeria; Perini, Laura; Pernegger, Heinz; Perrino, Roberto; Perrodo, Pascal; Persembe, Seda; Peshekhonov, Vladimir; Peters, Krisztian; Petersen, Brian; Petersen, Jorgen; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Petschull, Dennis; Petteni, Michele; Pezoa, Raquel; Phan, Anna; Phillips, Peter William; Piacquadio, Giacinto; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Piec, Sebastian Marcin; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinder, Alex; Pinfold, James; Pinto, Belmiro; Pizio, Caterina; Plamondon, Mathieu; Pleier, Marc-Andre; Plotnikova, Elena; Poblaguev, Andrei; Poddar, Sahill; Podlyski, Fabrice; Poggioli, Luc; Poghosyan, Tatevik; Pohl, Martin; Polci, Francesco; Polesello, Giacomo; Policicchio, Antonio; Polini, Alessandro; Poll, James; Polychronakos, Venetios; Pomarede, Daniel Marc; Pomeroy, Daniel; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Portell Bueso, Xavier; Pospelov, Guennady; Pospisil, Stanislav; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Prabhu, Robindra; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Pravahan, Rishiraj; Prell, Soeren; Pretzl, Klaus Peter; Price, Darren; Price, Joe; Price, Lawrence; Prieur, Damien; Primavera, Margherita; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Prudent, Xavier; Przybycien, Mariusz; Przysiezniak, Helenka; Psoroulas, Serena; Ptacek, Elizabeth; Pueschel, Elisa; Purdham, John; Purohit, Milind; Puzo, Patrick; Pylypchenko, Yuriy; Qian, Jianming; Qin, Zhonghua; Quadt, Arnulf; Quarrie, David; Quayle, William; Quinonez, Fernando; Raas, Marcel; Radescu, Voica; Radloff, Peter; Rador, Tonguc; Ragusa, Francesco; Rahal, Ghita; Rahimi, Amir; Rahm, David; Rajagopalan, Srinivasan; Rammensee, Michael; Rammes, Marcus; Randle-Conde, Aidan Sean; Randrianarivony, Koloina; Rauscher, Felix; Rave, Tobias Christian; Raymond, Michel; Read, Alexander Lincoln; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Reinherz-Aronis, Erez; Reinsch, Andreas; Reisinger, Ingo; Rembser, Christoph; Ren, Zhongliang; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Resende, Bernardo; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter-Was, Elzbieta; Ridel, Melissa; Rijpstra, Manouk; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Rios, Ryan Randy; Riu, Imma; Rivoltella, Giancesare; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocha de Lima, Jose Guilherme; Roda, Chiara; Roda Dos Santos, Denis; Rodriguez, Diego; Roe, Adam; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romeo, Gaston; Romero Adam, Elena; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Anthony; Rose, Matthew; Rosenbaum, Gabriel; Rosenberg, Eli; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rosselet, Laurent; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexander; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Ruckert, Benjamin; Ruckstuhl, Nicole; Rud, Viacheslav; Rudolph, Christian; Rudolph, Gerald; Rühr, Frederik; Ruggieri, Federico; Ruiz-Martinez, Aranzazu; Rumyantsev, Leonid; Runge, Kay; Rurikova, Zuzana; Rusakovich, Nikolai; Rutherfoord, John; Ruwiedel, Christoph; Ruzicka, Pavel; Ryabov, Yury; Ryan, Patrick; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sadeh, Iftach; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Sakamoto, Hiroshi; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvachua Ferrando, Belén; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Samset, Björn Hallvard; Sanchez, Arturo; Sanchez Martinez, Victoria; Sandaker, Heidi; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Tanya; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sansoni, Andrea; Santamarina Rios, Cibran; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Saraiva, João; Sarangi, Tapas; Sarkisyan-Grinbaum, Edward; Sarri, Francesca; Sartisohn, Georg; Sasaki, Osamu; Sasao, Noboru; Satsounkevitch, Igor; Sauvage, Gilles; Sauvan, Emmanuel; Sauvan, Jean-Baptiste; Savard, Pierre; Savinov, Vladimir; Savu, Dan Octavian; Sawyer, Lee; Saxon, David; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scallon, Olivia; Scannicchio, Diana; Scarcella, Mark; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schäfer, Uli; Schaepe, Steffen; Schaetzel, Sebastian; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R. Dean; Schamov, Andrey; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Scherzer, Max; Schiavi, Carlo; Schieck, Jochen; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitz, Martin; Schöning, André; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schram, Malachi; Schroeder, Christian; Schroer, Nicolai; Schultens, Martin Johannes; Schultes, Joachim; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Jan; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwemling, Philippe; Schwienhorst, Reinhard; Schwierz, Rainer; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciolla, Gabriella; Scott, Bill; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Sellden, Bjoern; Sellers, Graham; Seman, Michal; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Seuster, Rolf; Severini, Horst; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shank, James; Shao, Qi Tao; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Sherman, Daniel; Sherwood, Peter; Shibata, Akira; Shichi, Hideharu; Shimizu, Shima; Shimojima, Makoto; Shin, Taeksu; Shiyakova, Maria; Shmeleva, Alevtina; Shochet, Mel; Short, Daniel; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silbert, Ohad; Silva, José; Silver, Yiftah; Silverstein, Daniel; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simmons, Brinick; Simoniello, Rosa; Simonyan, Margar; Sinervo, Pekka; Sinev, Nikolai; Sipica, Valentin; Siragusa, Giovanni; Sircar, Anirvan; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinnari, Louise Anastasia; Skottowe, Hugh Philip; Skovpen, Kirill; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Ben Campbell; Smith, Douglas; Smith, Kenway; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snow, Steve; Snow, Joel; Snyder, Scott; Sobie, Randall; Sodomka, Jaromir; Soffer, Abner; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solfaroli Camillocci, Elena; Solodkov, Alexander; Solovyanov, Oleg; Soni, Nitesh; Sopko, Vit; Sopko, Bruno; Sosebee, Mark; Soualah, Rachik; Soukharev, Andrey; Spagnolo, Stefania; Spanò, Francesco; Spighi, Roberto; Spigo, Giancarlo; Spila, Federico; Spiwoks, Ralf; Spousta, Martin; Spreitzer, Teresa; Spurlock, Barry; St Denis, Richard Dante; Stahlman, Jonathan; Stamen, Rainer; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staude, Arnold; Stavina, Pavel; Steele, Genevieve; Steinbach, Peter; Steinberg, Peter; Stekl, Ivan; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoerig, Kathrin; Stoicea, Gabriel; Stonjek, Stefan; Strachota, Pavel; Stradling, Alden; Straessner, Arno; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strang, Michael; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Strong, John; Stroynowski, Ryszard; Strube, Jan; Stugu, Bjarne; Stumer, Iuliu; Stupak, John; Sturm, Philipp; Styles, Nicholas Adam; Soh, Dart-yin; Su, Dong; Subramania, Halasya Siva; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suita, Koichi; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Yu; Suzuki, Yuta; Svatos, Michal; Swedish, Stephen; Sykora, Ivan; Sykora, Tomas; Sánchez, Javier; Ta, Duc; Tackmann, Kerstin; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takahashi, Yuta; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tamsett, Matthew; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Satoshi; Tanaka, Shuji; Tanasijczuk, Andres Jorge; Tani, Kazutoshi; Tannoury, Nancy; Tapprogge, Stefan; Tardif, Dominique; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tassi, Enrico; Tatarkhanov, Mous; Tayalati, Yahya; Taylor, Christopher; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teinturier, Marthe; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Terada, Susumu; Terashi, Koji; Terron, Juan; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thioye, Moustapha; Thoma, Sascha; Thomas, Juergen; Thompson, Emily; Thompson, Paul; Thompson, Peter; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tian, Feng; Tibbetts, Mark James; Tic, Tomáš; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tique Aires Viegas, Florbela De Jes; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Toggerson, Brokk; Tojo, Junji; Tokár, Stanislav; Tokunaga, Kaoru; Tokushuku, Katsuo; Tollefson, Kirsten; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tonoyan, Arshak; Topfel, Cyril; Topilin, Nikolai; Torchiani, Ingo; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alesandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiakiris, Menelaos; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsung, Jieh-Wen; Tsuno, Soshi; Tsybychev, Dmitri; Tua, Alan; Tudorache, Alexandra; Tudorache, Valentina; Tuggle, Joseph; Turala, Michal; Turecek, Daniel; Turk Cakir, Ilkay; Turlay, Emmanuel; Turra, Ruggero; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Tzanakos, George; Uchida, Kirika; Ueda, Ikuo; Ueno, Ryuichi; Ugland, Maren; Uhlenbrock, Mathias; Uhrmacher, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Unno, Yoshinobu; Urbaniec, Dustin; Usai, Giulio; Uslenghi, Massimiliano; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vahsen, Sven; Valenta, Jan; Valente, Paolo; Valentinetti, Sara; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; van der Graaf, Harry; van der Kraaij, Erik; Van Der Leeuw, Robin; van der Poel, Egge; van der Ster, Daniel; van Eldik, Niels; van Gemmeren, Peter; van Vulpen, Ivo; Vanadia, Marco; Vandelli, Wainer; Vaniachine, Alexandre; Vankov, Peter; Vannucci, Francois; Vari, Riccardo; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vassilakopoulos, Vassilios; Vazeille, Francois; Vazquez Schroeder, Tamara; Vegni, Guido; Veillet, Jean-Jacques; Veloso, Filipe; Veness, Raymond; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinek, Elisabeth; Vinogradov, Vladimir; Virchaux, Marc; Virzi, Joseph; Vitells, Ofer; Viti, Michele; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Adrian; Vokac, Petr; Volpi, Guido; Volpi, Matteo; Volpini, Giovanni; von der Schmitt, Hans; von Loeben, Joerg; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorwerk, Volker; Vos, Marcel; Voss, Rudiger; Voss, Thorsten Tobias; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vu Anh, Tuan; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Wolfgang; Wagner, Peter; Wahlen, Helmut; Wahrmund, Sebastian; Wakabayashi, Jun; Walch, Shannon; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wall, Richard; Waller, Peter; Wang, Chiho; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Joshua C; Wang, Rui; Wang, Song-Ming; Wang, Tan; Warburton, Andreas; Ward, Patricia; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Anthony; Waugh, Ben; Weber, Marc; Weber, Michele; Weber, Pavel; Weidberg, Anthony; Weigell, Philipp; Weingarten, Jens; Weiser, Christian; Wellenstein, Hermann; Wells, Phillippa; Wenaus, Torre; Wendland, Dennis; Weng, Zhili; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Werth, Michael; Wessels, Martin; Wetter, Jeffrey; Weydert, Carole; Whalen, Kathleen; Wheeler-Ellis, Sarah Jane; White, Andrew; White, Martin; White, Sebastian; Whitehead, Samuel Robert; Whiteson, Daniel; Whittington, Denver; Wicek, Francois; Wicke, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wijeratne, Peter Alexander; Wildauer, Andreas; Wildt, Martin Andre; Wilhelm, Ivan; Wilkens, Henric George; Will, Jonas Zacharias; Williams, Eric; Williams, Hugh; Willis, William; Willocq, Stephane; Wilson, John; Wilson, Michael Galante; Wilson, Alan; Wingerter-Seez, Isabelle; Winkelmann, Stefan; Winklmeier, Frank; Wittgen, Matthias; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Wei-Cheng; Wooden, Gemma; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wraight, Kenneth; Wright, Catherine; Wright, Michael; Wrona, Bozydar; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wulf, Evan; Wynne, Benjamin; Xella, Stefania; Xiao, Meng; Xie, Song; Xu, Chao; Xu, Da; Yabsley, Bruce; Yacoob, Sahal; Yamada, Miho; Yamaguchi, Hiroshi; Yamamoto, Akira; Yamamoto, Kyoko; Yamamoto, Shimpei; Yamamura, Taiki; Yamanaka, Takashi; Yamaoka, Jared; Yamazaki, Takayuki; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Un-Ki; Yang, Yi; Yang, Zhaoyu; Yanush, Serguei; Yao, Liwen; Yao, Yushu; Yasu, Yoshiji; Ybeles Smit, Gabriel Valentijn; Ye, Jingbo; Ye, Shuwei; Yilmaz, Metin; Yoosoofmiya, Reza; Yorita, Kohei; Yoshida, Riktura; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, Dantong; Yu, Jaehoon; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zajacova, Zuzana; Zanello, Lucia; Zaytsev, Alexander; Zeitnitz, Christian; Zeller, Michael; Zeman, Martin; Zemla, Andrzej; Zendler, Carolin; Zenin, Oleg; Ženiš, Tibor; Zinonos, Zinonas; Zenz, Seth; Zerwas, Dirk; Zevi della Porta, Giovanni; Zhan, Zhichao; Zhang, Dongliang; Zhang, Huaqiao; Zhang, Jinlong; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Long; Zhao, Tianchi; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Ning; Zhou, Yue; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhuravlov, Vadym; Zieminska, Daria; Zimmermann, Robert; Zimmermann, Simone; Zimmermann, Stephanie; Ziolkowski, Michael; Zitoun, Robert; Živković, Lidija; Zmouchko, Viatcheslav; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zutshi, Vishnu; Zwalinski, Lukasz

    2013-07-16

    The results of a search for pair production of the lighter scalar partners of top quarks in 2.05 fb-1 of pp collisions at $\\sqrt{s}$ =7 TeV using the ATLAS experiment at the LHC are reported. Scalar top quarks are searched for in events with two same flavour opposite-sign leptons (electrons or muons) with invariant mass consistent with the Z boson mass, large missing transverse momentum and jets in the final state. At least one of the jets is identified as originating from a b-quark. No excess over Standard Model expectations is found. The results are interpreted in the framework of R-parity conserving, gauge mediated Supersymmetry breaking `natural' scenarios, where the neutralino is the next-to-lightest supersymmetric particle. Scalar top quark masses up to 310 GeV are excluded for the lightest neutralino mass between 115 GeV and 230 GeV at 95% confidence level, reaching an exclusion of the scalar top quark mass of 330 GeV for the lightest neutralino mass of 190 GeV. Scalar top quark masses below 240 GeV ar...

  12. Search for Scalar Top Quark Pair Production in Natural Gauge Mediated Supersymmetry Models with the ATLAS Detector in $pp$ Collisions at $\\sqrt{s}=$~7~TeV

    CERN Document Server

    The ATLAS collaboration

    2012-01-01

    The results of a search for pair production of the lighter scalar partners of top quarks ($\\tone$) in 2.05 fb-1 of $pp$ collisions at $\\sqrt{s}=7$~TeV using the ATLAS experiment are reported. Scalar top quarks are searched for in events with two same flavour opposite-sign leptons ($e,\\mu$) with invariant mass consistent with the $Z$ boson mass, large missing transverse momentum and jets in the final state. At least one of the jets is identified as originating from a $b$-quark. No excess over Standard Model expectations is found. The results are interpreted in the framework of $R$-parity conserving, gauge-mediated Supersymmetry breaking `natural' scenarios where the neutralino ($\\tilde{\\chi}_{1}^{0}$) is the next-to-lightest supersymmetric particle. Scalar top quark masses up to 310~GeV are excluded for 115~GeV~$< m_{\\tilde{\\chi}_{1}^{0}}<$~230~GeV at 95\\% confidence-level, reaching an exclusion of $m_{\\tone}<$~330~GeV for $m_{\\tilde{\\chi}_{1}^{0}}=190$~GeV.

  13. Impact of naturally spawning captive-bred Atlantic salmon on wild populations: depressed recruitment and increased risk of climate-mediated extinction.

    Science.gov (United States)

    McGinnity, Philip; Jennings, Eleanor; DeEyto, Elvira; Allott, Norman; Samuelsson, Patrick; Rogan, Gerard; Whelan, Ken; Cross, Tom

    2009-10-22

    The assessment report of the 4th International Panel on Climate Change confirms that global warming is strongly affecting biological systems and that 20-30% of species risk extinction from projected future increases in temperature. It is essential that any measures taken to conserve individual species and their constituent populations against climate-mediated declines are appropriate. The release of captive bred animals to augment wild populations is a widespread management strategy for many species but has proven controversial. Using a regression model based on a 37-year study of wild and sea ranched Atlantic salmon (Salmo salar) spawning together in the wild, we show that the escape of captive bred animals into the wild can substantially depress recruitment and more specifically disrupt the capacity of natural populations to adapt to higher winter water temperatures associated with climate variability. We speculate the mechanisms underlying this seasonal response and suggest that an explanation based on bio-energetic processes with physiological responses synchronized by photoperiod is plausible. Furthermore, we predict, by running the model forward using projected future climate scenarios, that these cultured fish substantially increase the risk of extinction for the studied population within 20 generations. In contrast, we show that positive outcomes to climate change are possible if captive bred animals are prevented from breeding in the wild. Rather than imposing an additional genetic load on wild populations by releasing maladapted captive bred animals, we propose that conservation efforts should focus on optimizing conditions for adaptation to occur by reducing exploitation and protecting critical habitats. Our findings are likely to hold true for most poikilothermic species where captive breeding programmes are used in population management.

  14. Intake of butter naturally enriched with cis9,trans11 conjugated linoleic acid reduces systemic inflammatory mediators in healthy young adults.

    Science.gov (United States)

    Penedo, Letícia A; Nunes, Juliana C; Gama, Marco Antônio S; Leite, Paulo Emilio C; Quirico-Santos, Thereza F; Torres, Alexandre G

    2013-12-01

    A conjugated linoleic acid (CLA) depletion-repletion study was carried out to investigate the effects of dietary c9,t11 CLA on C-reactive protein, transcription factor NFκB, metalloproteinases 2 and 9, inflammatory mediators (adiponectin, TNFα, IL-2, IL-4, IL-8, IL-10), body composition, and erythrocyte membrane composition in healthy normal-weight human adults. CLA depletion was achieved through an 8-week period of restricted dairy fat intake (depletion phase; CLA intake was 5.2±5.8 mg/day), followed by an 8-week period in which individuals consumed 20 g/day of butter naturally enriched with c9,t11 CLA (repletion phase; CLA intake of 1020±167 mg/day). The participants were 29 healthy adult volunteers (19 women and 10 men, aged 22 to 36 years), with body mass index between 18.0 and 29.9 kg m(-2). Blood samples were collected at baseline and at the end of both depletion and repletion phases. The content of CLA in erythrocytes decreased during CLA-depletion and increased during CLA-repletion. Intake of CLA-enriched butter increased the serum levels of anti-inflammatory IL-10 but reduced transcription factor NFκB in blood and serum levels of TNFα, IL-2, IL-8 and inactive metalloproteinase-9. Moreover, reduced activity of metalloproteinases 2 and 9 in serum was observed during the CLA-repletion period. In contrast, intake of CLA-enriched butter had no effects on body composition (DXA analysis) as well as on serum levels of adiponectin, C-reactive protein, and IL-4. Taken together, our results indicate that the intake of a c9,t11 CLA-enriched butter by normal-weight subjects induces beneficial changes in immune modulators associated with sub-clinical inflammation in overweight individuals. © 2013.

  15. Plant–plant interactions mediate the plastic and genotypic response of Plantago asiatica to CO2: an experiment with plant populations from naturally high CO2 areas

    Science.gov (United States)

    van Loon, Marloes P.; Rietkerk, Max; Dekker, Stefan C.; Hikosaka, Kouki; Ueda, Miki U.; Anten, Niels P. R.

    2016-01-01

    Background and Aims The rising atmospheric CO2 concentration ([CO2]) is a ubiquitous selective force that may strongly impact species distribution and vegetation functioning. Plant–plant interactions could mediate the trajectory of vegetation responses to elevated [CO2], because some plants may benefit more from [CO2] elevation than others. The relative contribution of plastic (within the plant’s lifetime) and genotypic (over several generations) responses to elevated [CO2] on plant performance was investigated and how these patterns are modified by plant–plant interactions was analysed. Methods Plantago asiatica seeds originating from natural CO2 springs and from ambient [CO2] sites were grown in mono stands of each one of the two origins as well as mixtures of both origins. In total, 1944 plants were grown in [CO2]-controlled walk-in climate rooms, under a [CO2] of 270, 450 and 750 ppm. A model was used for upscaling from leaf to whole-plant photosynthesis and for quantifying the influence of plastic and genotypic responses. Key Results It was shown that changes in canopy photosynthesis, specific leaf area (SLA) and stomatal conductance in response to changes in growth [CO2] were mainly determined by plastic and not by genotypic responses. We further found that plants originating from high [CO2] habitats performed better in terms of whole-plant photosynthesis, biomass and leaf area, than those from ambient [CO2] habitats at elevated [CO2] only when both genotypes competed. Similarly, plants from ambient [CO2] habitats performed better at low [CO2], also only when both genotypes competed. No difference in performance was found in mono stands. Conclusion The results indicate that natural selection under increasing [CO2] will be mainly driven by competitive interactions. This supports the notion that plant–plant interactions have an important influence on future vegetation functioning and species distribution. Furthermore, plant performance was mainly

  16. Plant-plant interactions mediate the plastic and genotypic response of Plantago asiatica to CO2 : an experiment with plant populations from naturally high CO2 areas

    NARCIS (Netherlands)

    van Loon, Marloes P; Rietkerk, Max; Dekker, Stefan C; Hikosaka, Kouki; Ueda, Miki U; Anten, Niels P R

    2016-01-01

    Background and Aims The rising atmospheric CO2 concentration ([CO2]) is a ubiquitous selective force that may strongly impact species distribution and vegetation functioning. Plant–plant interactions could mediate the trajectory of vegetation responses to elevated [CO2], because some plants may

  17. Characteristics of Cell-mediated, Anti-listerial Immunity Induced by A Naturally Avirulent Listeria monocytogenes Serotype 4a Strain HCC23

    Science.gov (United States)

    The characteristics of cell-mediated, anti-listerial immune response initiated by an avirulent Listeria monocytogenes serotype 4a strain HCC23 was assessed. Similar to virulent strain EGD, avirulent strain HCC23 grew readily within macrophage-like J774 cells, but nonhemolytic strain ATCC 15313 did n...

  18. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 × 2 factorial Mendelian randomization study.

    Science.gov (United States)

    Ference, Brian A; Majeed, Faisal; Penumetcha, Raju; Flack, John M; Brook, Robert D

    2015-04-21

    Considerable uncertainty exists as to whether lowering low-density lipoprotein cholesterol (LDL-C) by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) receptor with ezetimibe, either alone or in combination with a 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitor (statin), will reduce the risk of coronary heart disease (CHD). This study evaluated the effect of naturally random allocation to lower LDL-C mediated by polymorphisms in the NPC1L1 gene (target of ezetimibe), the HMGCR gene (target of statins), or both (target of combination therapy) on the risk of CHD. We constructed NPC1L1 and HMGCR genetic LDL-C scores to naturally randomize participants into 4 groups: reference, lower LDL-C mediated by NPC1L1 polymorphisms, lower LDL-C mediated by HMGCR polymorphisms, or lower LDL-C mediated by polymorphisms in both NPC1L1 and HMGCR. We compared the risk of CHD (fatal or nonfatal myocardial infarction) among each group using a 2 × 2 factorial mendelian randomization study design. A total of 108,376 persons (10,464 CHD events) from 14 studies were included. There were no significant differences in baseline characteristics among the 4 groups, thus confirming that allocation was random. Compared to the reference group, the NPC1L1 group had 2.4 mg/dl lower LDL-C and 4.8% lower risk of CHD (odds ratio [OR]: 0.952, 95% confidence interval [CI]: 0.920 to 0.985); whereas the HMGCR group had 2.9 mg/dl lower LDL-C and a similar 5.3% lower risk of CHD (OR: 0.947, 95% CI: 0.909 to 0.986). The group with lower LDL-C mediated by both NPC1L1 and HMGCR polymorphisms had 5.8 mg/dl additively lower LDL-C and a 10.8% log-linearly additive lower risk of CHD (OR: 0.892, 95% CI: 0.854 to 0.932). The effect of lower LDL-C on the risk of CHD mediated by polymorphisms in NPC1L1, HMGCR, or both is approximately the same per unit lower LDL-C and log-linearly proportional to the absolute exposure to lower LDL-C. Copyright © 2015 American College of Cardiology Foundation

  19. The use of simulated or concentrated natural solar radiation for the TiO2-mediated photodecomposition of Basagran, diquat, and diuron

    International Nuclear Information System (INIS)

    Kinkennon, A.E.; Green, D.B.; Hutchinson, B.

    1995-01-01

    Suspensions of TiO 2 were illuminated with simulated or concentrated solar radiation to mineralize solutions of the herbicides Basagran, Diquat, and Diuron. The design of a functional recirculating system is reported. Decomposition rates were significantly increased when concentrated solar radiation was used. Decomposition rates also depend on the compound studied. This study demonstrates the possibility of using high intensity concentrated solar radiation for the TiO 2 -mediated photocatalytic decomposition of water-borne organic wastes. (author)

  20. Peer Mediated Instruction and Intervention (PMII type Classwide Peer Tutoring (CWPT and Academics Ability of Natural Science-Biology in Vocational High School

    Directory of Open Access Journals (Sweden)

    Hamsiah Hamsiah

    2014-06-01

    Full Text Available Peer Mediated Instruction and Intervention (PMII tipe Classwide Peer Tutoring (CWPTdan Kemampuan Akademik pada Pembelajaran IPA Biologi SMK Abstract: Learning science in SMK 1 Bontang still dominated by conventional learning strategy is a method of learning with lecture. This has an impact on learning outcomes of cognitive science that tends biology is still low because the students have not been trained become independent learners, thus learning innovation PMII CWPT types can be used as a breakthrough to develop the cognitive learning. This study was conducted to determine the application CWPT strategies and academic skills in science teaching vocational Biology. Quasi-experimental research with pretest-posttest design Nonequivalent Control Group. Results of the study, namely: (1 there CWPT effect on the cognitive learning, (2 no influence academic ability to cognitive learning outcomes, and (3 there is no interaction effect between learning strategy and the academic ability toward the cognitive learning. Key Words: peer-mediated instruction and intervention, classwide peer tutoring, academic skills, cognitive learning outcomes Abstrak: Pembelajaran IPA di SMKN 1 Bontang masih didominasi dengan strategi belajar konvensio-nal yaitu metode belajar dengan ceramah. Hal ini berdampak terhadap hasil belajar kognitif IPA biolo-gi yang cendrung masih rendah karena siswa belum terlatih menjadi pebelajar yang mandiri, sehingga inovasi pembelajaran PMII tipe CWPT dapat digunakan sebagai terobosan untuk mengembangkan  hasil belajar kognitif. Penelitian ini dilakukan untuk mengetahui penerapan strategi CWPT dan kemam-puan akademik pada pembelajaran IPA Biologi SMK. Penelitian eksperimen semu dengan rancangan pretest-posttest Nonequivalent Control Group. Hasil penelitian, yaitu: (1 ada pengaruh CWPT ter-hadap hasil belajar kognitif,  (2 ada  pengaruh  kemampuan akademik terhadap hasil belajar kognitif, dan (3 tidak ada  pengaruh interaksi antara

  1. Differential effects of IL-2 and IL-21 on expansion of the CD4+ CD25+ Foxp3+ T regulatory cells with redundant roles in natural killer cell mediated antibody dependent cellular cytotoxicity in chronic lymphocytic leukemia.

    Science.gov (United States)

    Gowda, Aruna; Ramanunni, Asha; Cheney, Carolyn; Rozewski, Darlene; Kindsvogel, Wayne; Lehman, Amy; Jarjoura, David; Caligiuri, Michael; Byrd, John C; Muthusamy, Natarajan

    2010-01-01

    CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the novel common gamma chain cytokine interleukin (IL)-21 on primary B cells from CLL patients. Since members of this family of cytokines are known to exhibit their effects on diverse immune cells, we have examined the effects of IL-21 on CLL patient derived regulatory T cell (Treg) induction, expansion and the inhibitory effect on natural killer cells in vitro. We demonstrate here the expression of IL-21 receptor in CD4(+)CD25(High) regulatory cells from CLL patients. In contrast to IL-2, the IL-21 cytokine failed to mediate expansion of regulatory T cells or induced expression of Foxp3 in CD4(+)CD25(Intermediate) or CD4(+)CD25(Dim/-) T cells in whole blood derived from CLL patients. Interestingly, in contrast to their differential effects on expansion of the CD4(+)CD25(+)Foxp3(+)T cells, IL-2 and IL-21 exhibited a redundant role in Treg mediated suppression of NK cell mediated antibody dependent cytotoxicity function. Given the infusion related toxicities and pro-survival effect of IL-2 in CLL, these studies provide a rationale to explore IL-21 as an alternate gamma chain cytokine in CLL therapy.

  2. Language, knowledge, and mystical mediation: magic, clergy and intervention on the nature in the quotidian and representations in Medieval West - doi: 10.4025/actascieduc.v34i1.15881

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Mendes Pereira

    2012-05-01

    Full Text Available The Reading of documents of ecclesiastical source produced during Middle Ages provides the very clear percept of the presence of various categories of mediators between the natural world and mystical forces, in the daily routine of the western men. On the one hand, there were the wizards, expert supposedly endowed with special knowledge, who used as a resource various forms of exercise of divinatory arts and techniques of manipulation of elements of nature. During Middle Ages the ecclesiastical discourse searched opposing to their actions the knowledge and the achievements of the ‘true’ agents of sacred one, those who were organized in an ordo apart of the rest of society, ordoclericorum, enjoyed the privilege of access to the reading and writing of Latin. The concept of the clergy with which the Christian Church intended to qualify their members brought implicitly a cultural value which unified and distinguished them from the first ones. However, in the eyes of the people, the magical agents, as much as the clergies were endowed with specialized knowledge which granted to them the exercise of strange powers to the common mortals and made it possible for them controlling impersonal forces capable of altering the course of events. It is our intention to discuss the relationship between language, knowledge, and mystical Mediation in the current representations of magical agents and clergies in Middle Ages. 

  3. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

    Directory of Open Access Journals (Sweden)

    Klingelhoeffer Christoph

    2012-05-01

    Full Text Available Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L. The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50 values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L, was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L. Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves

  4. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

    Science.gov (United States)

    2012-01-01

    Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50) values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA) in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L), was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT) became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L). Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide

  5. NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton

    Directory of Open Access Journals (Sweden)

    Van Thai Ha

    2014-01-01

    Full Text Available AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO/prostaglandin (PG E2 production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2 in lipopolysaccharide- (LPS- treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS, cyclooxygenase- (COX- 2, and interleukin- (IL- 1β in LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBα and IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBα and AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation.

  6. Gluten-free diet does not influence the occurrence and the Th1/Th17-Th2 nature of immune-mediated diseases in patients with coeliac disease.

    Science.gov (United States)

    Imperatore, Nicola; Rispo, Antonio; Capone, Pietro; Donetto, Sara; De Palma, Giovanni Domenico; Gerbino, Nicolò; Rea, Matilde; Caporaso, Nicola; Tortora, Raffaella

    2016-07-01

    Coeliac disease (CD) is the most common Th1-mediated enteropathy, frequently associated with other immune-mediated disorders (IMD). To evaluate: (1) the prevalence of IMD at the time of and after CD diagnosis; (2) a possible change in immune response to gluten free diet (GFD); (3) the potential role of GFD in reducing and/or preventing IMD in CD. Prospective study including all consecutive adult CD patients who underwent investigations for Th1-Th17/Th2-IMD at the time of CD diagnosis and after a 5-year follow-up period. 1255 CD were enrolled. Of these, 257 patients (20.5%) showed IMD at the time of CD diagnosis, with 58.4% presenting a Th1/Th17-IMD. After a 5-year follow-up period, 682 patients (54.3%) showed new IMD despite GFD. Of these, 57.3% presented a Th1/Th17-IMD and 42.7% a Th2-IMD (p=0.8). When compared the prevalence of each type of IMD before and after CD diagnosis, we did not identify any significant "switch" from Th1/Th17- to Th2-IMD or vice versa. The number of patients with Th1/Th17- and/or Th2-IMD increased during the GFD period (20.5% vs 54.3%; p<0.01; OR 1.9). The prevalence of IMD at the time of CD diagnosis is high and it seems to increase in the follow-up period despite GFD. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  7. Hegel's conceptions of mediation

    OpenAIRE

    O'Connor, Brian

    1999-01-01

    Given its centrality to the intellectual thought processes through which the great structures of logic, nature, and spirit are unfolded it is clear that mediation is vital to the very possibility of Hegel's encyclopaedic philosophy. Yet Hegel gives little specific explanation of the concept of mediation. Surprisingly, it has been the subject of even less attention by scholars of Hegel. Nevertheless it is casually used in discussions of Hegel and post-Hegelian philosophy as though its meaning ...

  8. Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yufeng; Zhang, Xueshu; Zhao, Tuo; Li, Wei; Xiang, Jim, E-mail: jim.xiang@saskcancer.ca

    2013-08-16

    Highlights: •CD8{sup +}25{sup +} regulatory T cells secrete tolerogenic exosomes. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4{sup +}25{sup +} and CD8{sup +}25{sup +} regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8{sup +}25{sup +} Tr cells from C57BL/6 mouse naive CD8{sup +} T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO{sub Tr}) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO{sub Tr} had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC{sub OVA}) plus Tr cells or EXO{sub Tr}, and then assessed OVA-specific CD8{sup +} T cell responses using PE-H-2K{sup b}/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10{sub OVA} melanoma cells. We demonstrated that DC{sub OVA}-stimulated CD8{sup +} T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC{sub OVA} (p < 0.05) in immunized mice with co-injection of Tr cells and EXO{sub Tr}, respectively. Our results indicate that natural CD8{sup +}25{sup +} Tr cell-released EXOs, alike CD8{sup +}25{sup +} Tr cells, can inhibit CD8{sup +} T cell responses and antitumor immunity. Therefore, EXOs derived from

  9. Fremy’s Salt-Mediated Oxidative Addition. A New Approach in the Total Synthesis of Naturally Dipetalolactone and Its Immunomodulatory Activity

    Directory of Open Access Journals (Sweden)

    Yasser Selim

    2013-09-01

    Full Text Available The structure of the natural dipyranocoumarin dipetalolactone has been confirmed by an unambiguous synthetic route from resorcinol. This sequence was initiated by a pyran ring formation step which introduced the 3-chloro-3-methylbut-1-yne moiety. Then, the expected product undergoes a Fremy’s salt-meditated oxidative addition followed by ring closure to yield dipetalolactone. Dipetalolactone was also found to have immunological activity in a mouse carcinoma S180-bearing mice cell line.

  10. Staphylococcus-mediated T-cell activation and spontaneous natural killer cell activity in the absence of major histocompatibility complex class II molecules

    Science.gov (United States)

    Chapes, S. K.; Hoynowski, S. M.; Woods, K. M.; Armstrong, J. W.; Beharka, A. A.; Iandolo, J. J.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    We used major histocompatibility complex class II antigen-deficient transgenic mice to show that in vitro natural killer cell cytotoxicity and T-cell activation by staphylococcal exotoxins (superantigens) are not dependent upon the presence of major histocompatibility complex class II molecules. T cells can be activated by exotoxins in the presence of exogenously added interleukin 1 or 2 or in the presence of specific antibody without exogenously added cytokines.

  11. Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors

    Directory of Open Access Journals (Sweden)

    Floyd Hassenrück

    2018-01-01

    Full Text Available The antibody-dependent cell-mediated cytotoxicity (ADCC of the anti-CD20 monoclonal antibodies (mAbs rituximab and obinutuzumab against the cell line Raji and isolated CLL cells and its potential impairment by kinase inhibitors (KI was determined via lactate dehydrogenase release or calcein retention, respectively, using genetically modified NK92 cells expressing CD16-176V as effector cells. Compared to peripheral blood mononuclear cells, recombinant effector cell lines showed substantial alloreactivity-related cytotoxicity without addition of mAbs but afforded determination of ADCC with reduced interassay variability. The cytotoxicity owing to alloreactivity was less susceptible to interference by KI than the ADCC of anti-CD20 mAbs, which was markedly diminished by ibrutinib, but not by idelalisib. Compared to rituximab, the ADCC of obinutuzumab against primary CLL cells showed approximately 30% higher efficacy and less interference with KI. Irreversible BTK inhibitors at a clinically relevant concentration of 1 μM only weakly impaired the ADCC of anti-CD20 mAbs, with less influence in combinations with obinutuzumab than with rituximab and by acalabrutinib than by ibrutinib or tirabrutinib. In summary, NK cell line-based assays permitted the sensitive detection of ADCC of therapeutic anti-CD20 mAbs against CLL cells and of the interference of KI with this important killing mechanism.

  12. Effect of temperature on the microstructure of fat globules and the immunoglobulin-mediated interactions between fat and bacteria in natural raw milk creaming.

    Science.gov (United States)

    D'Incecco, P; Ong, L; Pellegrino, L; Faoro, F; Barbiroli, A; Gras, S

    2018-02-02

    Natural creaming of raw milk is the first step in production of Grana Padano and Parmigiano Reggiano Protected Denomination of Origin cheeses. This process decreases the fat content and plays an important role in the removal of clostridia species that may cause late-blowing defects in ripened cheeses. Partial coalescence of fat globules-that may influence fat behavior in cheese making and affect the microstructure of fat in the final cheese product-was observed at creaming temperatures higher than 22°C by confocal laser scanning microscopy. The widespread practice of heating of milk at 37°C before creaming at 8°C resulted in important changes in the size distribution of fat globules in raw milk, potentially altering the ability of fat to entrap clostridia spores. We investigated the role of immunoglobulin classes in both the clustering of fat globules and the agglutination of Clostridium tyrobutyricum to fat globules during creaming. Immunogold labeling and transmission electron microscopy showed that IgA and IgM but not IgG were involved in both clustering and agglutination. Both vegetative cells and spores were clearly shown to agglutinate to fat droplets, a process that was suppressed by thermal denaturation of the immunoglobulins. The debacterization of raw milk through natural creaming was improved by the addition of purified immunoglobulins. Overall, these findings provide not only a better understanding of the phenomena occurring during the natural creaming but also practical insights into how the process of creaming may be optimized in cheese production plants. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  13. Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells

    Science.gov (United States)

    Reyes-Zurita, Fernando J.; Rufino-Palomares, Eva E.; García-Salguero, Leticia; Peragón, Juan; Medina, Pedro P.; Parra, Andrés; Cascante, Marta; Lupiáñez, José A.

    2016-01-01

    Maslinic acid (MA) is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner. MA triggered a series of effects associated with apoptosis, including the cleavage of caspases -8 and -3, and increased the levels of t-Bid within a few hours of its addition to the culture medium. MA had no effect on the expression of the Bax protein, release of cytochrome-c or on the mitochondrial membrane potential. This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line. Our results suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells MA seems to work independently of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin. PMID:26751572

  14. Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro

    DEFF Research Database (Denmark)

    Feng, Shan; Madsen, Suzi H; Viller, Natasja N

    2015-01-01

    as well as to inflammatory sites associated with enhanced bone erosion, including the joints of patients with rheumatoid arthritis, little is known about the impact NK cells may have on mature osteoclasts and bone erosion. We studied the interaction between human NK cells and autologous monocyte......Osteoclasts reside on bone and are the main bone resorbing cells playing an important role in bone homeostasis, while natural killer (NK) cells are bone-marrow-derived cells known to play a crucial role in immune defence against viral infections. Although mature NK cells traffic through bone marrow...... decreased bone erosion. Suppression of bone erosion requires contact between NK cells and osteoclasts, but soluble factors also play a minor role. Antibodies masking leucocyte function-associated antigen-1, DNAX accessory molecule-1 or tumour necrosis factor-related apoptosis-inducing ligand enhance...

  15. Natural killer (NK) and NK-like cells at mucosal epithelia: Mediators of anti-microbial defense and maintenance of tissue integrity

    Science.gov (United States)

    Colonna, M.

    2011-01-01

    Natural killer (NK) cells are innate lymphocytes that play important roles in the defense against microbial pathogens through secretion of IFN-γ and recognition and lysis of virally or bacterially infected host cells. A recently identified population of NK-like cells that shares characteristics of both NK cells and lymphoid tissue inducer (LTi) cells promotes innate immune responses in epithelial tissue through the secretion of IL-22. In contrast to classical NK cells, NK-like cells are localized preferentially at mucosal sites, such as the intestinal mucosa. In this review, we consider the function of NK and NK-like cells in anti-microbial defense as well as the maintenance of tissue integrity in the mucosal epithelium of the intestine, lung, and female reproductive tract. Current experimental evidence supports an important protective role for IL-22-producing NK-like cells during intestinal infections, whereas classical NK cells are crucial in the early defense against many pathogens in the respiratory tract. NK cells isolated from the pregnant uterus differ significantly in phenotype and function from those at other tissue locations. Uterine NK cells clearly contribute to the tissue remodeling that takes place during placentation, but their role in anti-microbial defense remains largely undefined. PMID:24516732

  16. A requirement for CD45 distinguishes Ly49D-mediated cytokine and chemokine production from killing in primary natural killer cells

    Science.gov (United States)

    Huntington, Nicholas D.; Xu, Yuekang; Nutt, Stephen L.; Tarlinton, David M.

    2005-01-01

    Engagement of receptors on the surface of natural killer (NK) cells initiates a biochemical cascade ultimately triggering cytokine production and cytotoxicity, although the interrelationship between these two outcomes is currently unclear. In this study we investigate the role of the cell surface phosphatase CD45 in NK cell development and intracellular signaling from activating receptors. Stimulation via the major histocompatibility complex I–binding receptor, Ly49D on CD45 −/− primary NK cells resulted in the activation of phosphoinositide-3-kinase and normal cytotoxicity but failed to elicit a range of cytokines and chemokines. This blockage is associated with impaired phosphorylation of Syk, Vav1, JNK, and p38, which mimics data obtained using inhibitors of the src-family kinases (SFK). These data, supported by analogous findings after CD16 and NKG2D stimulation of CD45 −/− primary NK cells, place CD45 upstream of SFK in NK cells after stimulation via immunoreceptor tyrosine-based activation motif-containing receptors. Thus we identify CD45 as a pivotal enzyme in eliciting a precise subset of NK cell responses. PMID:15867094

  17. Flexible Mediation Analysis With Multiple Mediators.

    Science.gov (United States)

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. The natural compound codonolactone attenuates TGF-β1-mediated epithelial-to-mesenchymal transition and motility of breast cancer cells.

    Science.gov (United States)

    Fu, Jianjiang; Ke, Xiaoqin; Tan, Songlin; Liu, Ting; Wang, Shan; Ma, Junchao; Lu, Hong

    2016-01-01

    Codonolactone (CLT), a natural product, is the major bioactive component of Atractylodes lancea, and also found in a range of other medical herbs, such as Codonopsis pilosula, Chloranthus henryi Hemsl and Atractylodes macrocephala Koidz. This sesquiterpene lactone has been demonstrated to exhibit a range of activities, including anti-allergic activity, anti-inflammatory, anticancer, gastroprotective and neuroprotective activity. Previously, we found that CLT showed significant anti-metastatic properties in vitro and in vivo. In order to determine whether EMT-involved mechanisms contribute to the anti-metastatic effects of CLT, we checked the anti-EMT properties of CLT and its potential mechanisms. Here it was demonstrated that CLT inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, downregulation of TGF-β signaling was associated with the anti-EMT properties of CLT. Data from western blotting showed that, in breast cancer cells, TGF-β1 stimulated the activation of Runx2, and CLT blocked the activation of Runx2. Finally, to verify whether CLT-induced EMT inhibition leads to suppression of metastatic potential, the effects of CLT on cell invasion and migration were determined. It was found that TGF-β1-induced migration and invasion was significantly blocked by CLT in both MDA-MB-231 and MDA-MB-468 cells. Collectively, our findings demonstrated that CLT inhibited programming of EMT in vitro and in vivo, resulting in inhibition of motility of metastatic breast cancer cells. The inhibitory effect of CLT was due to its ability to inhibit TGF-β signaling and Runx2 phosphorylation.

  19. An RNA aptamer possessing a novel monovalent cation-mediated fold inhibits lysozyme catalysis by inhibiting the binding of long natural substrates.

    Science.gov (United States)

    Padlan, Camille S; Malashkevich, Vladimir N; Almo, Steve C; Levy, Matthew; Brenowitz, Michael; Girvin, Mark E

    2014-04-01

    RNA aptamers are being developed as inhibitors of macromolecular and cellular function, diagnostic tools, and potential therapeutics. Our understanding of the physical nature of this emerging class of nucleic acid-protein complexes is limited; few atomic resolution structures have been reported for aptamers bound to their protein target. Guided by chemical mapping, we systematically minimized an RNA aptamer (Lys1) selected against hen egg white lysozyme. The resultant 59-nucleotide compact aptamer (Lys1.2minE) retains nanomolar binding affinity and the ability to inhibit lysozyme's catalytic activity. Our 2.0-Å crystal structure of the aptamer-protein complex reveals a helical stem stabilizing two loops to form a protein binding platform that binds lysozyme distal to the catalytic cleft. This structure along with complementary solution analyses illuminate a novel protein-nucleic acid interface; (1) only 410 Å(2) of solvent accessible surface are buried by aptamer binding; (2) an unusually small fraction (∼18%) of the RNA-protein interaction is electrostatic, consistent with the limited protein phosphate backbone contacts observed in the structure; (3) a single Na(+) stabilizes the loops that constitute the protein-binding platform, and consistent with this observation, Lys1.2minE-lysozyme complex formation takes up rather than displaces cations at low ionic strength; (4) Lys1.2minE inhibits catalysis of large cell wall substrates but not catalysis of small model substrates; and (5) the helical stem of Lys1.2minE can be shortened to four base pairs (Lys1.2minF) without compromising binding affinity, yielding a 45-nucleotide aptamer whose structure may be an adaptable protein binding platform.

  20. Natural deep eutectic solvent mediated pretreatment of rice straw: bioanalytical characterization of lignin extract and enzymatic hydrolysis of pretreated biomass residue.

    Science.gov (United States)

    Kumar, Adepu K; Parikh, Bhumika S; Pravakar, Mohanty

    2016-05-01

    The present investigation demonstrated pretreatment of lignocellulosic biomass rice straw using natural deep eutectic solvents (NADESs), and separation of high-quality lignin and holocellulose in a single step. Qualitative analysis of the NADES extract showed that the extracted lignin was of high purity (>90 %), and quantitative analysis showed that nearly 60 ± 5 % (w/w) of total lignin was separated from the lignocellulosic biomass. Addition of 5.0 % (v/v) water during pretreatment significantly enhanced the total lignin extraction, and nearly 22 ± 3 % more lignin was released from the residual biomass into the NADES extract. X-ray diffraction studies of the untreated and pretreated rice straw biomass showed that the crystallinity index ratio was marginally decreased from 46.4 to 44.3 %, indicating subtle structural alterations in the crystalline and amorphous regions of the cellulosic fractions. Thermogravimetric analysis of the pretreated biomass residue revealed a slightly higher T dcp (295 °C) compared to the T dcp (285 °C) of untreated biomass. Among the tested NADES reagents, lactic acid/choline chloride at molar ratio of 5:1 extracted maximum lignin of 68 ± 4 mg g(-1) from the rice straw biomass, and subsequent enzymatic hydrolysis of the residual holocellulose enriched biomass showed maximum reducing sugars of 333 ± 11 mg g(-1) with a saccharification efficiency of 36.0 ± 3.2 % in 24 h at 10 % solids loading.

  1. Polyclonal type II natural killer T cells require PLZF and SAP for their development and contribute to CpG-mediated antitumor response

    Science.gov (United States)

    Zhao, Jie; Weng, Xiufang; Bagchi, Sreya; Wang, Chyung-Ru

    2014-01-01

    CD1d-restricted natural killer T (NKT) cells are innate-like T cells with potent immunomodulatory function via rapid production of both Th1 and Th2 cytokines. NKT cells comprise well-characterized type I NKT cells, which can be detected by α-galactosylceramide-loaded CD1d tetramers, and less-studied type II NKT cells, which do not recognize α-galactosylceramide. Here we characterized type II NKT cells on a polyclonal level by using a Jα18-deficient IL-4 reporter mouse model. This model allows us to track type II NTK cells by the GFP+TCRβ+ phenotype in the thymus and liver. We found type II NKT cells, like type I NKT cells, exhibit an activated phenotype and are dependent on the transcriptional regulator promyelocytic leukemia zinc finger (PLZF) and the adaptor molecule signaling lymphocyte activation molecule-associated protein (SAP) for their development. Type II NKT cells are potently activated by β-D-glucopyranosylceramide (β-GlcCer) but not sulfatide or phospholipids in a CD1d-dependent manner, with the stimulatory capacity of β-GlcCer influenced by acyl chain length. Compared with type I NKT cells, type II NKT cells produce lower levels of IFN-γ but comparable amounts of IL-13 in response to polyclonal T-cell receptor stimulation, suggesting they may play different roles in regulating immune responses. Furthermore, type II NKT cells can be activated by CpG oligodeoxynucletides to produce IFN-γ, but not IL-4 or IL-13. Importantly, CpG-activated type II NKT cells contribute to the antitumor effect of CpG in the B16 melanoma model. Taken together, our data reveal the characteristics of polyclonal type II NKT cells and their potential role in antitumor immunotherapy. PMID:24550295

  2. Natural gas; Gas Natural

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Carlos A.; Moraes, Claudia C.D. [Eletricidade de Sao Paulo S.A. (ELETROPAULO), Sao Paulo, SP (Brazil); Fonseca, Carlos H.F. [Centrais Eletricas de Santa Catarina S.A., Florianopolis, SC (Brazil); Silva, Clecio Fabricio da; Alves, Ricardo P. [Companhia Paranaense de Energia (COPEL), Curitiba, PR (Brazil); Sposito, Edivaldo Soares; Hulle, Lutero [Espirito Santo Centrais Eletricas S.A. (ESCELSA), Vitoria, ES (Brazil); S. Martins, Icaro da [Centrais Eletricas do Norte do Brasil S.A. (ELETRONORTE), Belem, PA (Brazil); Vilhena, Joao Luiz S. de [Companhia Energetica de Minas Gerais (CEMIG), Belo Horizonte, MG (Brazil); Fagundes, Zaluar Aquino [Companhia Estadual de Energia Eletrica do Estado do Rio Grande do Sul, Porto Alegre, RS (Brazil)

    1996-12-31

    An increase in the consumption of natural gas in Brazil is an expected fact in what concerns energetic planning. This work presents the existing situation in what concerns natural gas utilization in the main world economies, as well as an analysis of the participation of this fuel among the energy final consumption per sources. The Brazilian consumption of natural gas is also analysed as well as the international agreement between Brazil and Bolivia for natural gas commercialization. Some legal, institutional and political aspects related to natural gas commercialization are also discussed. Finally, several benefits to be brought by the utilization of natural gas are presented 10 refs., 3 tabs.

  3. Protective Effect of Panax notoginseng Root Water Extract against Influenza A Virus Infection by Enhancing Antiviral Interferon-Mediated Immune Responses and Natural Killer Cell Activity

    Directory of Open Access Journals (Sweden)

    Jang-Gi Choi

    2017-11-01

    Full Text Available Influenza is an acute respiratory illness caused by the influenza A virus, which causes economic losses and social disruption mainly by increasing hospitalization and mortality rates among the elderly and people with chronic diseases. Influenza vaccines are the most effective means of preventing seasonal influenza, but can be completely ineffective if there is an antigenic mismatch between the seasonal vaccine virus and the virus circulating in the community. In addition, influenza viruses resistant to antiviral drugs are emerging worldwide. Thus, there is an urgent need to develop new vaccines and antiviral drugs against these viruses. In this study, we conducted in vitro and in vivo analyses of the antiviral effect of Panax notoginseng root (PNR, which is used as an herbal medicine and nutritional supplement in Korea and China. We confirmed that PNR significantly prevented influenza virus infection in a concentration-dependent manner in mouse macrophages. In addition, PNR pretreatment inhibited viral protein (PB1, PB2, HA, NA, M1, PA, M2, and NP and viral mRNA (NS1, HA, PB2, PA, NP, M1, and M2 expression. PNR pretreatment also increased the secretion of pro-inflammatory cytokines [tumor necrosis factor alpha and interleukin 6] and interferon (IFN-beta and the phosphorylation of type-I IFN-related proteins (TANK-binding kinase 1, STAT1, and IRF3 in vitro. In mice exposed to the influenza A H1N1 virus, PNR treatment decreased mortality by 90% and prevented weight loss (by approximately 10% compared with the findings in untreated animals. In addition, splenocytes from PNR-administered mice displayed significantly enhanced natural killer (NK cell activity against YAC-1 cells. Taking these findings together, PNR stimulates an antiviral response in murine macrophages and mice that protects against viral infection, which may be attributable to its ability to stimulate NK cell activity. Further investigations are needed to reveal the molecular

  4. Mediatized Humanitarianism

    DEFF Research Database (Denmark)

    Vestergaard, Anne

    2014-01-01

    The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts to legiti......The article investigates the implications of mediatization for the legitimation strategies of humanitarian organizations. Based on a (full population) corpus of ~400 pages of brochure material from 1970 to 2007, the micro-textual processes involved in humanitarian organizations' efforts...... legitimation by accountancy, legitimation by institutionalization, and legitimation by compensation. The analysis relates these changes to a problem of trust associated with mediatization through processes of mediation....

  5. Further studies on the nature of postsynaptic dopamine uptake and metabolism in rat striatum: sodium dependency and investigation of a possible role for carrier-mediated uptake into serotonin neurons

    Energy Technology Data Exchange (ETDEWEB)

    Schoepp, D.D.; Azzaro, A.J.

    1985-06-01

    The nature of postsynaptic sites involved in the uptake and metabolism of striatal 3,4-dihydroxyphenylethylamine (dopamine, DA) was investigated. The accumulation of (/sup 3/H)DA (10(-7) M) into slices of rat striatum was found to be greatly dependent on the presence of sodium ion in the incubation medium. However, the formation of the (/sup 3/H)dihydroxyphenylacetic acid (DOPAC) and (/sup 3/H)homovanillic acid (HVA) was only partially reduced in the absence of sodium. Inhibition of carrier-mediated DA neuronal uptake with nomifensine significantly decreased DA accumulation (18% of control) and (/sup 3/H)DOPAC formation (62% of control), but enhanced (/sup 3/H)HVA production (143% of control). Inhibition of the 5-hydroxytryptamine (5-HT, serotonin) neuronal uptake system with fluoxetine (10(-6) M) or selective 5-HT neuronal lesions with 5,7-dihydroxytryptamine (5,7-DHT) had no effect on (/sup 3/H)DOPAC or (/sup 3/H)HVA formed from (/sup 3/H)DA in the presence or absence of nomifensine. These results demonstrate that the uptake and subsequent metabolism of striatal DA to DOPAC and HVA is only partially dependent on carrier-mediated uptake mechanism(s) requiring sodium ion. These data support our previous findings suggesting a significant role for synaptic glial cell deamination and O-methylation of striatal DA. Further, experiments with fluoxetine or 5,7-DHT suggest that 5-HT neurons do not significantly contribute in the synaptic uptake and metabolism of striatal DA.

  6. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  7. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...

  8. Mediation –Voluntary or Mandatory Procedure

    Directory of Open Access Journals (Sweden)

    Angelica ROSU

    2010-03-01

    Full Text Available Part of modifications brought through 370/2009 Act to the 192/2006 Law concerning mediation and structure of mediator profession have been interpreted as establishing a preliminary mediation procedure before intimating the courts of law, in civil and commercial matters. This interpretation is in excess of operative legal provisions. Although the law in modified form stipulates the compulsoriness of judicial authorities and other jurisdictional bodies to inform the parties about the possibility and the dvantages of using mediation procedure and the obligation to guide the parties to resort at mediation, this circumstances does not affect the mediation particular voluntary nature.

  9. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts....... In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  10. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  11. Axionic mirage mediation

    International Nuclear Information System (INIS)

    Nakamura, Shuntaro; Okumura, Ken-ichi; Yamaguchi, Masahiro

    2008-01-01

    Although mirage mediation is one of the most plausible mediation mechanisms of supersymmetry breaking, it suffers from two crucial problems. One is the μ/Bμ problem, and the second is the cosmological one. The former stems from the fact that the B parameter tends to be comparable with the gravitino mass, which is 2 orders of magnitude larger than the other soft masses. The latter problem is caused by the decay of the modulus whose branching ratio into the gravitino pair is sizable. In this paper, we propose a model of mirage mediation, in which Peccei-Quinn symmetry is incorporated. In this axionic mirage mediation, it is shown that the Peccei-Quinn symmetry breaking scale is dynamically determined around 10 10 GeV to 10 12 GeV due to the supersymmetry breaking effects, and the μ problem can be solved naturally. Furthermore, in our model, the lightest supersymmetric particle (LSP) is the axino, that is, the superpartner of the axion. The overabundance of the LSPs due to decays of the modulus/gravitino, which is the most serious cosmological difficulty in the mirage mediation, can be avoided if the axino is sufficiently light. The next-LSPs (NLSPs) produced by the gravitino decay eventually decay into the axino LSPs, yielding the dominant component of the axinos remaining today. It is shown that the axino with a mass of O(100) MeV is naturally realized, which can constitute the dark matter of the Universe, with a free-streaming length of the order of 0.1 Mpc. The saxion, the real scalar component of the axion supermultiplet, can also be cosmologically harmless due to the dilution of the modulus decay. The lifetime of the NLSP is relatively long, but much shorter than 1 sec, when the big-bang nucleosynthesis commences. The decay of the NLSP would provide intriguing collider signatures

  12. Platelet-derived TGF-β1 mediates the down-modulation of NKG2D expression and may be responsible for impaired natural killer (NK) cytotoxicity in women with endometriosis.

    Science.gov (United States)

    Guo, Sun-Wei; Du, Yanbo; Liu, Xishi

    2016-07-01

    when compared with that of women without endometriosis. Both the platelet activation rate and the TGF-β1 concentration in the PF correlated negatively with the NKG2D expression in NK cells isolated from the PF (r = -0.36, P cytotoxicity in freshly isolated NK cells were found to be significantly reduced if co-cultured with PF from women with endometriosis, but the TGF-β1 blockade effectively reverses the reduction. This study is limited by the cross-sectional nature of the study. NKG2D is known to potently activate NK cells, so potent that it even overrides inhibitory signals transduced by other inhibitory receptors. This is the first time we demonstrate that platelet-derived TGF-β1 may be responsible for reduced NKG2D expression as well as reduced cytotoxicity of NK cells in women with endometriosis. This study provides yet another piece of evidence that platelets play critical roles in the development of endometriosis, and anti-platelet treatment should improve NK cell functionality in treating endometriosis. Equally important, this study highlights the critical role of the lesion microenvironment in shaping NK cell-mediated anti-endometriotic immunity. This research was supported in part by grants 81270676 (S.-W.G.), 81471434 (S.-W.G.), 81530040 (S.-W.G.), and 81370695 (X.L.) from the National Natural Science Foundation of China, and grant 2013ZYJB0019 (X.L.) from Shanghai Municipal Commission of Health and Family Planning. None of the authors has anything to disclose. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Focus point supersymmetry in extended gauge mediation

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Ran [School of Physics, Nankai University,Tianjin 300071 (China); Li, Tianjun [State Key Laboratory of Theoretical Physics and Kavli Institute for Theoretical Physics (KITPC),Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190 (China); School of Physical Electronics, University of Electronic Science and Technology of China,Chengdu 610054 (China); Staub, Florian [Bethe Center for Theoretical Physics & Physikalisches Institut der Universität Bonn,Nußallee 12, 53115 Bonn (Germany); Zhu, Bin [School of Physics, Nankai University,Tianjin 300071 (China)

    2014-03-27

    We propose a small extension of the minimal gauge mediation through the combination of extended gauge mediation and conformal sequestering. We show that the focus point supersymmetry can be realized naturally, and the fine tuning is significantly reduced compared to the minimal gauge mediation and extended gauge mediation without focus point. The Higgs boson mass is around 125 GeV, the gauginos remain light, and the gluino is likely to be detected at the next run of the LHC. However, the multi-TeV squarks is out of the reach of the LHC. The numerical calculation for fine-tuning shows that this model remains natural.

  14. Focus point supersymmetry in extended gauge mediation

    International Nuclear Information System (INIS)

    Ding, Ran; Li, Tianjun; Staub, Florian; Zhu, Bin

    2014-01-01

    We propose a small extension of the minimal gauge mediation through the combination of extended gauge mediation and conformal sequestering. We show that the focus point supersymmetry can be realized naturally, and the fine tuning is significantly reduced compared to the minimal gauge mediation and extended gauge mediation without focus point. The Higgs boson mass is around 125 GeV, the gauginos remain light, and the gluino is likely to be detected at the next run of the LHC. However, the multi-TeV squarks is out of the reach of the LHC. The numerical calculation for fine-tuning shows that this model remains natural

  15. Natural killer cells in psoriasis.

    LENUS (Irish Health Repository)

    Tobin, A M

    2012-02-01

    Psoriasis is one of the most common immune-mediated disorders. There is evidence that it is mediated by Th1 and, more recently, Th17 cells. The cytokine pattern, particularly the dominance of TNF-alpha, implicates the innate immune system in psoriasis pathogenesis. Of the many components of the innate immune system known to be involved in psoriatic lesions, natural killer and natural killer T cells appear to have a unique role. We review the evidence supporting a role for natural killer cells in psoriasis.

  16. Natural soft leptogenesis

    International Nuclear Information System (INIS)

    Grossman, Yuval; Kitano, Ryuichiro; Murayama, Hitoshi

    2005-01-01

    Successful soft leptogenesis requires small B-terms for the right-handed sneutrinos and a large CP violating phase between the A- and B-terms. We show that this situation is realized naturally within the framework of gauge mediated supersymmetry breaking. The A-term is dominated by contribution from gauge mediation, while supergravity effects are more important for the B-term. The different origins naturally explain simultaneously the smallness of the B-term and the large CP violating phase. The most stringent bounds on the model come from the cosmological gravitino problem. We find a viable parameter region with very light gravitino m 3/2 ∼< 16 eV, providing a consistent framework for supersymmetry phenomenology, soft leptogenesis and cosmology

  17. PLURALIZING NATURE

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel

    2014-01-01

    not necessary mean planning for a one common nature. As exemplified by the River Aire Re-naturalization Project (2002-2015), landscape architecture might provide an alternative approach to nature restoration that is more site specific and allows for multiple interpretations to coexist. In the presentation...

  18. Natural resolution of inflammation.

    Science.gov (United States)

    Freire, Marcelo O; Van Dyke, Thomas E

    2013-10-01

    Inflammation is a protective response essential for maintaining human health and for fighting disease. As an active innate immune reaction to challenge, inflammation gives rise to clinical cardinal signs: rubor, calor, dolor, tumor and functio laesa. Termination of acute inflammation was previously recognized as a passive process; a natural decay of pro-inflammatory signals. We now understand that the natural resolution of inflammation involves well-integrated, active, biochemical programs that return tissues to homeostasis. This review focuses on recent advances in the understanding of the role of endogenous lipid mediators that modulate cellular fate and inflammation. Biosynthesis of eicosanoids and other lipids in exudates coincides with changes in the types of inflammatory cells. Resolution of inflammation is initiated by an active class switch in lipid mediators, such as classic prostaglandins and leukotrienes, to the production of proresolution mediators. Endogenous pro-resolving lipid mediators, including arachidonic acid-derived lipoxins, aspirin-triggered lipoxins, ω3-eicosapentaenoic acid-derived resolvins of the E-series, docosahexaenoic acid-derived resolvins of the D-series, protectins and maresins, are biosynthesized during the resolution phase of acute inflammation. Depending on the type of injury and the type of tissue, the initial cells that respond are polymorphonuclear leukocytes, monocytes/macrophages, epithelial cells or endothelial cells. The selective interaction of specific lipid mediators with G protein-coupled receptors expressed on innate immune cells (e.g. G protein-coupled receptor 32, lipoxin A4 receptor/formyl peptide receptor2, chemokine-like receptor 1, leukotriene B4 receptor type 1 and cabannoid receptor 2) induces cessation of leukocyte infiltration; vascular permeability/edema returns to normal with polymorphonuclear neutrophil death (mostly via apoptosis), the nonphlogistic infiltration of monocyte/macrophages and the removal

  19. Determination of natural and depleted uranium in urine at the ppt level: an interlaboratory analytical exercise

    International Nuclear Information System (INIS)

    D'Agostino, P.A.; Ough, E.A.; Glover, S.E.; Vallerand, A.L.

    2002-10-01

    An analytical exercise was initiated in order to determine those analytical procedures with the capacity to measure uranium isotope ratios ( 238 U/ 235 U) in urine samples containing less that 1μ uranium /L urine. A host laboratory was tasked with the preparation of six sets (12 samples per set) of synthetic urine samples spiked with varying amounts of natural and depleted (0.2% 235 U) uranium. The sets of samples contained total uranium in the range 25 ng U/L urine to 770 ng U/L urine, with isotope ratios ( 238 U/ 235 U) from 137.9 (natural uranium) to 215 (∼50% depleted uranium). Sets of samples were shipped to five testing laboratories (four Canadian and one European) for total and isotopic assay. The techniques employed in the analyses included sector field inductively coupled plasma mass spectrometry (ICP-SF-MS), quadrupole inductively coupled plasma mass spectrometry (ICP-Q-MS), thermal ionization mass spectrometry (TIMS) and neutron activation analysis (NAA). Full results were obtained from three testing labs (ICP-SF-MS, ICP-Q-MS and TIMS). Their results, plus partial results from the NAA lab, have been included in this report. Total uranium and isotope ratio results obtained from ICP-SF-MS and ICP-Q-MS were in good agreement with the host lab values. Neutron activation analysis and TIMS reported total uranium concentrations that differed from the host lab. An incomplete set of isotopic ratios was obtained from the NAA lab with some results reporting enriched uranium (% 235 U > 0.7). Based on the reported results, the four analytical procedures were ranked: ICP-SF-MS (1), ICP-Q-MS (2), TIMS (3) and NAA (4). (author)

  20. PLURALIZING NATURE

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel

    2014-01-01

    Denmark is widely recognised for its democratic approach to planning and the idea of planning for the common good. This interest in the common good and common values seems also to be reflected in the way which nature restoration is planned and managed – one common nature directed by the public...... authorities. But nature restoration is far from being a neural undertaking. Just like any other type of heritage production it can be the source of dissonance – ‘our’ nature is not necessary ‘their’ nature. Often this dissonance is managed in ways, which are not particular sensitive to site......-specificity. As exemplified by the Skjern River Restoration Project (1999-2003), one interpretation of the landscape sometimes suppresses other valid interpretations neglecting its diverse history. However, evidence from Switzerland suggests that planning for the common good, in the case of nature restoration, does...

  1. Temporal naturalism

    Science.gov (United States)

    Smolin, Lee

    2015-11-01

    Two people may claim both to be naturalists, but have divergent conceptions of basic elements of the natural world which lead them to mean different things when they talk about laws of nature, or states, or the role of mathematics in physics. These disagreements do not much affect the ordinary practice of science which is about small subsystems of the universe, described or explained against a background, idealized to be fixed. But these issues become crucial when we consider including the whole universe within our system, for then there is no fixed background to reference observables to. I argue here that the key issue responsible for divergent versions of naturalism and divergent approaches to cosmology is the conception of time. One version, which I call temporal naturalism, holds that time, in the sense of the succession of present moments, is real, and that laws of nature evolve in that time. This is contrasted with timeless naturalism, which holds that laws are immutable and the present moment and its passage are illusions. I argue that temporal naturalism is empirically more adequate than the alternatives, because it offers testable explanations for puzzles its rivals cannot address, and is likely a better basis for solving major puzzles that presently face cosmology and physics. This essay also addresses the problem of qualia and experience within naturalism and argues that only temporal naturalism can make a place for qualia as intrinsic qualities of matter.

  2. Natural Philosophy

    OpenAIRE

    Blair, Ann M.

    2006-01-01

    Natural philosophy” is often used by European historians as an umbrella term to designate the study of nature before it can easily be identified with what we call “science” today, to avoid the modern and potentially anachronistic connotations of that term. But “natural philosophy” (and its equivalents in different languages) was also an actor's category, a term commonly used throughout the early modern period and typically defined quite broadly as the study of natural bodies. As the central ...

  3. Bioethics mediation: the role and importance of nursing advocacy.

    Science.gov (United States)

    Schlairet, Maura C

    2009-01-01

    Ethics consultations are utilized in health care to identify and manage conflict, difficult decision-making, and ethical issues. In bioethics mediation, a more updated approach using interpersonal, mediative, conflict management, and dispute resolution skills is merged with ethical principles to manage dilemmas arising in healthcare settings. This article argues, based on a professional obligation to advocate for the good of the client, that nurses must assume leadership roles in mediation processes. Nurses can initiate and fully participate in formal bioethics mediation and other mediative interventions. Nurse administrators can work to evolve existing ethics consult models to mediation models. Nonetheless, mediative efforts of individual nurses must be grounded in realization of the multifactorial nature of conflict and dilemma in healthcare settings. Multidisciplinary mediative interventions, framed by sound institutional policies, may best serve the complex needs of ethically vulnerable clients. To best advocate for these at-risk clients, nurses must assume various leadership roles in mediation processes.

  4. Combined gauge-mediated and anomaly-mediated supersymmetry breaking and conformal sequestering

    International Nuclear Information System (INIS)

    Sundrum, Raman

    2005-01-01

    Anomaly-mediated supersymmetry breaking in the context of 4D conformally sequestered models is combined with Poppitz-Trivedi D-type gauge-mediation. The implementation of the two mediation mechanisms naturally leads to visible soft masses at the same scale so that they can cooperatively solve the μ and flavor problems of weak scale supersymmetry, as well as the tachyonic-slepton problem of pure anomaly-mediation. The tools are developed in a modular fashion for more readily fitting into the general program of optimizing supersymmetric dynamics in hunting for the most attractive weak scale phenomenologies combined with Planck-scale plausibility

  5. Framing nature

    NARCIS (Netherlands)

    Jansen, Peter

    2017-01-01

    This PhD thesis is about communication concerning nature in the Netherlands. The purpose of this exploratory study is to take both a theoretical and an empirical look at whether (implicit) religious elements play a role in this communication about nature in the Netherlands.

    In this PhD

  6. natural theology

    African Journals Online (AJOL)

    p1243322

    ancient Greece. The aim of this article is not to propose a new natural theology; nor does it seek to resurrect older models. It is necessary, however, to examine the extent to ... In studies like this one the South African context is relevant, as Barth is ... human reason to reach knowledge about God's nature and works insofar as.

  7. Nature Watch

    Indian Academy of Sciences (India)

    Nature Watch. When Dragons Fly ... K A Subramanian. A Natural History of Odonata. We have all held them by their wings, made them lift pebbles from our palms, tied their tails to paper flags and watched them flyaway, wondering all the while where and how they lived and what they did. I only knew that we called them ...

  8. Nature Detectives

    Science.gov (United States)

    Harr, Natalie; Lee, Richard E.; Jr.

    2010-01-01

    Richard Louv's "Last Child in the Woods" (2008) added to a growing consensus to get children outside and experiencing nature. Using ideas from place-based education, the authors present a simple year-long project that brings science, nature, and other curriculum standards to life right in your school yard. With a focus on journaling, this project…

  9. Matematica Natural.

    Science.gov (United States)

    Lozano, Patricia; Medearis, Linda

    Matematica Natural (Natural Mathematics) is a mathematics curriculum for young children based on the assumption that they learn mathematics through concrete, real life, relevant experiences and that educational differences rather than cultural differences influence math achievement. The curriculum uses hands-on materials and activities to teach…

  10. Natur formet

    DEFF Research Database (Denmark)

    Søberg, Martin

    2011-01-01

    Anmeldelse af Malene Hauxner, "Fra naturlig natur til SUPERNATUR – Europæisk landskabsarkitektur 1967-2007 set fra Danmark", Risskov: Ikaros Press, 2011.......Anmeldelse af Malene Hauxner, "Fra naturlig natur til SUPERNATUR – Europæisk landskabsarkitektur 1967-2007 set fra Danmark", Risskov: Ikaros Press, 2011....

  11. Framing nature

    NARCIS (Netherlands)

    Jansen, Peter

    2017-01-01

    This PhD thesis is about communication concerning nature in the Netherlands. The purpose of this exploratory study is to take both a theoretical and an empirical look at whether (implicit) religious elements play a role in this communication about nature in the Netherlands.   In this PhD thesis

  12. Dissonant Nature

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel

    2013-01-01

    Nature restoration is far from being a neural undertaking. Just like any other type of heritage production it can be the source of dissonance – ‘our’ nature is not necessary ‘their’ nature. Often this dissonance is managed in ways, which are not particular sensitive to site......-specificity. As exemplified by the Skjern River Restoration Project (1999-2003), one interpretation of the landscape sometimes suppresses other valid interpretations neglecting its diverse history. Landscape architecture might, however, provide an alternative approach to nature restoration that is more site specific...... and allows for multiple interpretations to coexist. Evidence can be found in the Re-naturalization of River Aire (2002-2015), a restoration project, which reveals approaches that could be labelled landscape architecture specific....

  13. Microbially mediated mineral carbonation

    Science.gov (United States)

    Power, I. M.; Wilson, S. A.; Dipple, G. M.; Southam, G.

    2010-12-01

    Mineral carbonation involves silicate dissolution and carbonate precipitation, which are both natural processes that microorganisms are able to mediate in near surface environments (Ferris et al., 1994; Eq. 1). (Ca,Mg)SiO3 + 2H2CO3 + H2O → (Ca,Mg)CO3 + H2O + H4SiO4 + O2 (1) Cyanobacteria are photoautotrophs with cell surface characteristics and metabolic processes involving inorganic carbon that can induce carbonate precipitation. This occurs partly by concentrating cations within their net-negative cell envelope and through the alkalinization of their microenvironment (Thompson & Ferris, 1990). Regions with mafic and ultramafic bedrock, such as near Atlin, British Columbia, Canada, represent the best potential sources of feedstocks for mineral carbonation. The hydromagnesite playas near Atlin are a natural biogeochemical model for the carbonation of magnesium silicate minerals (Power et al., 2009). Field-based studies at Atlin and corroborating laboratory experiments demonstrate the ability of a microbial consortium dominated by filamentous cyanobacteria to induce the precipitation of carbonate minerals. Phototrophic microbes, such as cyanobacteria, have been proposed as a means for producing biodiesel and other value added products because of their efficiency as solar collectors and low requirement for valuable, cultivable land in comparison to crops (Dismukes et al., 2008). Carbonate precipitation and biomass production could be facilitated using specifically designed ponds to collect waters rich in dissolved cations (e.g., Mg2+ and Ca2+), which would allow for evapoconcentration and provide an appropriate environment for growth of cyanobacteria. Microbially mediated carbonate precipitation does not require large quantities of energy or chemicals needed for industrial systems that have been proposed for rapid carbon capture and storage via mineral carbonation (e.g., Lackner et al., 1995). Therefore, this biogeochemical approach may represent a readily

  14. Writing Nature

    Directory of Open Access Journals (Sweden)

    Kristin Asdal

    2014-06-01

    Full Text Available This special issue of the Nordic Journal of Science and Technology Studies is interested in how nature, in different versions and forms, is invited into our studies, analyses, and stories. How is it that we “write nature”? How is it that we provide space for, and actually describe the actors, agents, or surroundings, in our stories and analyses? The articles in the issue each deal with different understandings of both the practices of writing and the introduction of various natures into these. In this introduction to the issue the editors engage with actor-network theory as a material semiotic resource for writing nature. We propose to foreground actor-network theory as a writing tool, at the expense of actor-network theory as a distinct vocabulary. In doing this and pointing out the semiotic origins to material-semiotics we also want to problematize a clear-cut material approach to writing nature.

  15. Natural Childbirth

    Science.gov (United States)

    ... Things That Help Feelings Expert Answers Q&A Movies & More for Teens Teens site Sitio para adolescentes ... the Pain? Print en español Parto natural Some women choose to give birth using no medications at ...

  16. Natural Communities

    Data.gov (United States)

    Kansas Data Access and Support Center — This dataset shows the locations of known tracts of high quality natural communities in Kansas, generalized to the PLSS section. It is not a compehensive dataset of...

  17. Pluralising Nature

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel

    2017-01-01

    Denmark is recognised for its democratic approach to planning, and for the idea of planning for the common good. This interest in the common good and in common values also seems to be reflected in the way that the restoration of nature is planned and managed, suggesting that there is one common...... “nature” that everyone can agree on. But nature restoration is far from being an unproblematic undertaking. As with any other type of heritage production, it can be the source of dissonance. As exemplified by the Skjern River Restoration Project, one perception of a landscape and its value as “nature” can...... suppress other valid perceptions, in conflict with the need for different groups of people to be able to identify with the same territory. However, planning for the common good, in the case of nature restoration, does not necessarily mean planning for one common nature. Understanding and working...

  18. Natural Propositions

    DEFF Research Database (Denmark)

    Stjernfelt, Frederik

    Preface -- Introduction -- The generality of signs -- Dicisigns -- Some consequences of the dicisign doctrine -- Dicisigns and cognition -- Natural propositions--the evolution of semiotic self-control -- Dicisigns beyond language -- Operational and optimal iconicity in Peirce's diagrammatology...

  19. Natural aphrodisiacs.

    Science.gov (United States)

    Shamloul, Rany

    2010-01-01

    The search for a remedy or a prescription that can enhance sexual function and/or treat male erectile dysfunction has been an obsession throughout known history. Whether it was an Eastern civilization or a Western one, religious or atheist, man's aspiration for a better or best "manhood" has been a history-time goal. This review will discuss the current research done on the most popular natural aphrodisiacs and examine the weight of evidence to support or discourage the use of any of these substances to enhance sexual desire and/or function. Review of the current evidence on the use of natural substances as aphrodisiacs. Efficacy of natural aphrodisiacs in enhancing sexual function in men and women. There is little evidence from literature to recommend the usage of natural aphrodisiacs for the enhancement of sexual desire and/or performance. Data on yohimbine's efficacy does not support the wide use of the drug, which has only mild effects in the treatment of psychogenic ED. Although there's a positive trend towards recommending ginseng as an effective aphrodisiac, however, more in depth studies involving large number of subjects and its mechanism of action are needed before definite conclusions could be reached. Data on the use of natural aphrodisiacs in women is limited. The current body of objective evidence does not support the use of any natural aphrodisiac as an effective treatment for male or female sexual dysfunctions. Potent men and men with ED will continue the search for natural aphrodisiacs despite the current disappointing data on their effectiveness. Care should be taken regarding the fraud addition of sildenafil analogues to natural aphrodisiacs.

  20. On the Sequence-Directed Nature of Human Gene Mutation: The Role of Genomic Architecture and the Local DNA Sequence Environment in Mediating Gene Mutations Underlying Human Inherited Disease

    Science.gov (United States)

    Cooper, David N.; Bacolla, Albino; Férec, Claude; Vasquez, Karen M.; Kehrer-Sawatzki, Hildegard; Chen, Jian-Min

    2011-01-01

    Different types of human gene mutation may vary in size, from structural variants (SVs) to single base-pair substitutions, but what they all have in common is that their nature, size and location are often determined either by specific characteristics of the local DNA sequence environment or by higher-order features of the genomic architecture. The human genome is now recognized to contain ‘pervasive architectural flaws’ in that certain DNA sequences are inherently mutation-prone by virtue of their base composition, sequence repetitivity and/or epigenetic modification. Here we explore how the nature, location and frequency of different types of mutation causing inherited disease are shaped in large part, and often in remarkably predictable ways, by the local DNA sequence environment. The mutability of a given gene or genomic region may also be influenced indirectly by a variety of non-canonical (non-B) secondary structures whose formation is facilitated by the underlying DNA sequence. Since these non-B DNA structures can interfere with subsequent DNA replication and repair, and may serve to increase mutation frequencies in generalized fashion (i.e. both in the context of subtle mutations and SVs), they have the potential to serve as a unifying concept in studies of mutational mechanisms underlying human inherited disease. PMID:21853507

  1. Nordic Mediation Reseach

    DEFF Research Database (Denmark)

    A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden.......A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden....

  2. Natural Disaster and Natural Selection

    OpenAIRE

    Uchida, Hirofumi; Miyakawa, Daisuke; Hosono, Kaoru; Ono, Arito; Uchino, Taisuke; Uesugi, Iichiro

    2013-01-01

    In this paper, we investigate whether a natural selection mechanism works for firm exit. By using data of firms after a devastating earthquake, the Greeat Tohoku Earthquake, we examine the impact of firm efficiency on firm exit both inside and outside the earthquake-affected areas. We find evidence suggesting that more efficeint firms are less likely to exit both inside and outside the affected areas, which supports the natural selection mechanism. However, we also find that the mechanism is ...

  3. Emancipating Nature

    DEFF Research Database (Denmark)

    Munk, Anders Kristian

    2012-01-01

    The issue of riverine flooding in the UK is closely tied up with computer simulations. Arguably, these modelling practices are ripe with the anticipation of nature. They aspire to pre-empt it, hence expect it to be ‘out there’, and ultimately work through formalized distillations of it – hydrodyn......The issue of riverine flooding in the UK is closely tied up with computer simulations. Arguably, these modelling practices are ripe with the anticipation of nature. They aspire to pre-empt it, hence expect it to be ‘out there’, and ultimately work through formalized distillations...... of it – hydrodynamic equations – which have their own anticipations and place their own demands on their modellers. Through the experience of a flood modelling apprenticeship I argue that the taking-place of such anticipations paradoxically relies on the birth of a hybrid, the model-modeller, and thus on a nature...

  4. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  5. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  6. Provincialising Nature

    DEFF Research Database (Denmark)

    Provincialising Nature: Multidisciplinary Approaches to the Politics of the Environment in Latin America offers a timely analysis of some of the crucial challenges, contradictions and promises within current environmental discourses and practices in the region. This book shows both challenging...... scenarios and original perspectives that have emerged in Latin America in relation to the globally urgent issues of climate change and the environmental crisis. Two interconnected analytical frameworks guide the discussions in the book: the relationship between nature, knowledge and identity and their role...

  7. Natural pedagogy.

    Science.gov (United States)

    Csibra, Gergely; Gergely, György

    2009-04-01

    We propose that human communication is specifically adapted to allow the transmission of generic knowledge between individuals. Such a communication system, which we call 'natural pedagogy', enables fast and efficient social learning of cognitively opaque cultural knowledge that would be hard to acquire relying on purely observational learning mechanisms alone. We argue that human infants are prepared to be at the receptive side of natural pedagogy (i) by being sensitive to ostensive signals that indicate that they are being addressed by communication, (ii) by developing referential expectations in ostensive contexts and (iii) by being biased to interpret ostensive-referential communication as conveying information that is kind-relevant and generalizable.

  8. Natural aerodynamics

    CERN Document Server

    Scorer, R S

    1958-01-01

    Natural Aerodynamics focuses on the mathematics of any problem in air motion.This book discusses the general form of the law of fluid motion, relationship between pressure and wind, production of vortex filaments, and conduction of vorticity by viscosity. The flow at moderate Reynolds numbers, turbulence in a stably stratified fluid, natural exploitation of atmospheric thermals, and plumes in turbulent crosswinds are also elaborated. This text likewise considers the waves produced by thermals, transformation of thin layer clouds, method of small perturbations, and dangers of extra-polation.Thi

  9. Veritable antiviral capacity of natural killer cells in chronic HBV infection: an argument for an earlier anti-virus treatment

    Directory of Open Access Journals (Sweden)

    Xiaoyan Li

    2017-10-01

    Full Text Available Abstract Background There is limited information on innate immunity, especially natural killer (NK cell function, in different chronic hepatitis B (CHB stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity. Methods A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ were classified according to the latest American Association for the Study of Liver Disease guidelines. Peripheral blood mononuclear cells from patients and healthy controls were tested for NK cell frequency, phenotype and function using flow cytometry. Results A significant decrease in activating receptor NKp44 and NKp46 expression and significant increase of exhaustion molecule Tim-3 expression were observed in NK cells from CHB patients. Reduced cytokine secretion and preserved or elevated cytotoxic function were also observed. Patients in the IT group exhibited comparable cytokine secretion and cytolytic capacity as age-matched IA patients. NK cell anti-viral functions were preserved in GZ patients. Some of the NK cell function in patients who were excluded from treatment by the current treatment guidelines was less compromised than patients who qualified for treatment. Conclusion Our findings provide evidence of veritable NK cell immunity during different natural history phases in treatment-naïve patients with chronic HBV Infection. Chronic HBV infection hindered NK cell function in CHB patients. However, the presumed IT and GZ statuses of CHB patients based on the clinical parameters may not accurately reflect the inner immune status of these patients and should be reconsidered. Some patients excluded from treatment by the current treatment guidelines may be able to be selected as candidates for treatment.

  10. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 2. Nature Watch Decline of a Montane Ecosystem. Kartik Shanker. Feature Article Volume 2 Issue 2 February 1997 pp 75-82. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/02/0075-0082 ...

  11. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 8. Nature Watch - Hornbills – Giants Among the Forest Birds. T R Shankar Raman Divya Mudappa. Feature Article Volume 3 Issue 8 August 1998 pp 56-65. Fulltext. Click here to view fulltext PDF. Permanent link:

  12. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 9; Issue 9. Nature Watch - Coral Reefs and their Fauna: An Underwater Fantasyland. Anuradha Bhat. Feature Article Volume 9 Issue 9 September 2004 pp 62-73. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Nature Watch

    Indian Academy of Sciences (India)

    Annual Meetings · Mid Year Meetings · Discussion Meetings · Public Lectures · Lecture Workshops · Refresher Courses · Symposia · Live Streaming. Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 7. Nature Watch - Tent-making Bats. N Gopukumar J Balasingh. Feature Article Volume 7 Issue ...

  14. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 3. Nature Watch Diversity of Bats. G Marimuthu. Feature Article Volume 1 Issue 3 March 1996 pp 103-110. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/001/03/0103-0110. Author Affiliations.

  15. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 5. Nature Watch Will the Meek Inherit the Earth? Kartik Shanker. Feature Article Volume 2 Issue 5 May 1997 pp 54-59. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/05/0054-0059 ...

  16. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 8. Nature Watch: On the Trail of Skinks of the Western Ghats. Anirudha Datta-Roy. Feature Article Volume 19 Issue 8 August 2014 pp 753-763. Fulltext. Click here to view fulltext PDF. Permanent link:

  17. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 3. Nature Watch Diversity of Bats. G Marimuthu. Feature Article Volume 1 Issue 3 March 1996 pp 103-110. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/001/03/0103-0110. Author Affiliations.

  18. Nature Watch

    Indian Academy of Sciences (India)

    After the 1960s man's attention was diverted towards the Thar ... effects also. The alluvial and inter-dunal plains have gypsiferous hard pen sediments, which are responsible for serious water logging and salinity-alkalinity problems. Moreover, natural surface drainage system is absent and the ground water is highly saline.

  19. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 8. Nature Watch - Secrets of the Shieldtails. Kartik Shanker. Feature Article Volume 1 Issue 8 August 1996 pp 64-70. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/001/08/0064-0070 ...

  20. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 7. Nature Watch - Singapore's Jurong BirdPark: A Study Model. Abraham Verghese. Feature Article Volume 6 Issue 7 July 2001 pp 74-88. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 7. Nature Watch - The Odyssey of the Olive Ridley. Kartik Shanker. Feature Article Volume 4 Issue 7 July 1999 pp 68-78. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/004/07/0068-0078 ...

  2. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 12. Nature Watch - Sarus Crane: On its Way to Extinction. Alok Kumar Mishra. Feature Article Volume 14 Issue 12 December 2009 pp 1206-1209. Fulltext. Click here to view fulltext PDF. Permanent link:

  3. Kritikkens natur

    DEFF Research Database (Denmark)

    Schatz-Jakobsen, Claus

    1999-01-01

    Artiklen introducerer det nye forskningsfelt inden for samtænkning af litteratur, kultur og natur, den såkaldt økologiske kritik, og kaster et kritisk blik på  dens brug af romantisk litteratur som proto-økologisk kanon....

  4. Nature Watch

    Indian Academy of Sciences (India)

    Nature Watch - Tracking Turtles through Time and Space. Kartik Shanker. General Article Volume 7 Issue 6 June 2002 ... Keywords. Turtles; animal navigation; conservation biology; nesting behaviour; telemetry. Author Affiliations. Kartik Shanker1. Wildlife Institute of India PO Box 18, Chandrabani Dehradun 248001, India.

  5. Nature Watch

    Indian Academy of Sciences (India)

    ... Lecture Workshops · Refresher Courses · Symposia · Live Streaming. Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 5. Nature Watch - Thinking Like a Tahr: When Males and Females go their Separate Ways. M D Madhusudan. Feature Article Volume 3 Issue 5 May 1998 pp 43-47 ...

  6. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 10. Nature Watch The Amazing Desert Gerbil. Ishwar Prakash. Feature Article Volume 2 Issue 10 October 1997 pp 54-61. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/10/0054-0061 ...

  7. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 3. Nature Watch: Symbiosis in Coastal Marine Communities. Neelam Pereira. Feature Article Volume 20 Issue 3 March 2015 pp 245-253. Fulltext. Click here to view fulltext PDF. Permanent link:

  8. Natural fibers

    Science.gov (United States)

    Craig M. Clemons; Daniel F. Caulfield

    2005-01-01

    The term “natural fibers” covers a broad range of vegetable, animal, and mineral fibers. However, in the composites industry, it usually refers to wood fiber and agrobased bast, leaf, seed, and stem fibers. These fibers often contribute greatly to the structural performance of the plant and, when used in plastic composites, can provide significant reinforcement. Below...

  9. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 8. Nature Watch - Secrets of the Shieldtails. Kartik Shanker. Feature Article Volume 1 Issue 8 August 1996 pp 64-70. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/001/08/0064-0070 ...

  10. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 10. Nature Watch - When Dragons Fly. K A Subramanian. Feature Article Volume 7 Issue 10 October 2002 pp 69-78. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/007/10/0069-0078 ...

  11. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 8. Nature Watch - The Treasures of the Night Sky. P N Shankar B S Shylaja. Feature Article Volume 6 Issue 8 August 2001 pp 82-89. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/006/08/0082- ...

  12. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 1. Nature Watch The Kokum Tree. M D Subash Chandran. Feature Article Volume 1 Issue 1 January 1996 pp 86-89. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/001/01/0086-0089 ...

  13. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 7. Nature Watch - On Observing the Night Sky. P N Shankar B S Shylaja. Feature Article Volume 6 Issue 7 July 2001 pp 89-96. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/006/07/0089-0096 ...

  14. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 4. Nature Watch The Ancient Mariners. Kartik Shanker. Feature Article Volume 1 Issue 4 April 1996 pp 50-57. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/001/04/0050-0057. Author Affiliations.

  15. Nature Watch

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... ... 20; Issue 1. Nature Watch: A Tale of Two Turtles. V Deepak. Feature Article Volume 20 Issue 1 January 2015 pp 47-54. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/020/01/0047-0054. Keywords. Ecology; endemic; India; turtles; tortoises; Western Ghats.

  16. Nature Watch

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 7. Nature Watch - The Odyssey of the Olive Ridley. Kartik Shanker. Feature Article Volume 4 Issue 7 July 1999 pp 68-78. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/004/07/0068-0078 ...

  17. General gauge mediation

    International Nuclear Information System (INIS)

    Meade, Patrick; Seiberg, Nathan; Shih, David

    2009-01-01

    We give a general definition of gauge mediated supersymmetry breaking which encompasses all the known gauge mediation models. In particular, it includes both models with messengers as well as direct mediation models. A formalism for computing the soft terms in the generic model is presented. Such a formalism is necessary in strongly-coupled direct mediation models where perturbation theory cannot be used. It allows us to identify features of the entire class of gauge mediation models and to distinguish them from specific signatures of various subclasses. (author)

  18. Bovine colostrum enhances natural killer cell activity and immune response in a mouse model of influenza infection and mediates intestinal immunity through toll-like receptors 2 and 4.

    Science.gov (United States)

    Wong, Eric B; Mallet, Jean-François; Duarte, Jairo; Matar, Chantal; Ritz, Barry W

    2014-04-01

    Oral administration of bovine colostrum affects intestinal immunity, including an increased percentage of natural killer (NK) cells. However, effects on NK cell cytotoxic activity and resistance to infection as well as a potential mechanism remain unclear. Therefore, we investigated the effects of bovine colostrum (La Belle, Inc, Bellingham, WA) on the NK cytotoxic response to influenza infection and on toll-like receptor (TLR) activity in a primary intestinal epithelial cell culture. We hypothesized that colostrum would increase NK cell activity and that TLR-2 and TLR-4 blocking would reduce interleukin 6 production by epithelial cells in response to contact stimulation with colostrum. Four-month-old female C57BL/6 mice were supplemented with 1 g of colostrum per kilogram of body weight before and after infection with influenza A virus (H1N1). Animals were assessed for weight loss, splenic NK cell activity, and lung virus titers. Colostrum-supplemented mice demonstrated less reduction in body weight after influenza infection, indicating a less severe infection, increased NK cell cytotoxicity, and less virus burden in the lungs compared with controls. Colostrum supplementation enhanced NK cell cytotoxicity and improved the immune response to primary influenza virus infection in mice. To investigate a potential mechanism, a primary culture of small intestine epithelial cells was then stimulated with colostrum. Direct activation of epithelial cells resulted in increased interleukin 6 production, which was inhibited with TLR-2 and TLR-4 blocking antibodies. The interaction between colostrum and immunity may be dependent, in part, on the interaction of colostrum components with innate receptors at the intestinal epithelium, including TLR-2 and TLR-4. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. IFN-α augments natural killer-mediated antibody-dependent cellular cytotoxicity of HIV-1-infected autologous CD4+ T cells regardless of major histocompatibility complex class 1 downregulation.

    Science.gov (United States)

    Tomescu, Costin; Tebas, Pablo; Montaner, Luis J

    2017-03-13

    We have previously shown that IFN-α stimulation augments direct natural killer (NK) cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon major histocompatibility complex class 1 (MHC-1) downregulation capacity. Here, we investigated if antibody-dependent cellular cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α prestimulation of NK cells could further enhance ADCC. Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1-infected patients (ART-suppressed or elite controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1-infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells. Total or NK-depleted peripheral blood mononuclear cells were used as effectors in the presence or absence of IFN-α prestimulation. Plasma from HIV-1-infected patients and monoclonal antibodies against gp120 could trigger NK-dependent ADCC lysis of viral isolates that were resistant to direct NK cell lysis following IFN-α stimulation. In contrast, viral isolates that exhibited potent MHC-I downregulation capacity could be lysed by NK cells through either IFN-α stimulated direct cytotoxicity or through ADCC. When utilized in combination, IFN-α prestimulation significantly augmented ADCC lysis of HIV-1-infected target cells and increased NK cell CD107a degranulation against gp120-coated ADCC targets (P cytotoxicity depending on MHC downregulation status.

  20. Unbounded Naturalism

    Directory of Open Access Journals (Sweden)

    Andrew Taggart

    2008-10-01

    Full Text Available nbsp;font face="Times, serif"font size="3"In the Anglo-American reception of John McDowellrsquo;s /font/fontfont face="Times, serif"font size="3"emMind and World/em/font/fontfont face="Times, serif"font size="3", there has been little attention paid to the developmental aspect of his lsquo;partially re-enchantedrsquo; naturalism. In lsquo;Naturalism Unboundedrsquo;, I argue that McDowellrsquo;s story of our normal upbringing (/font/fontfont face="Times, serif"font size="3"emBildung/em/font/fontfont face="Times, serif"font size="3" presents problems for his claim that we have a lsquo;standing obligationrsquo; to reflect on our perceptual experiences. I follow this critique up with a Hegelian-inspired attempt to retain and revise the vital points he makes about experience./font/font

  1. Jagtens natur

    DEFF Research Database (Denmark)

    Gjerris, Mickey; Borkfelt, Sune; Gamborg, Christian

    2017-01-01

    Jagt kan ses som en konfrontation mellem menneskeverdenen og den vilde natur. I dag kan det dog være svært at få øje på det vilde i naturen i et land som Danmark, hvor over 60 % af det samlede areal anvendes til landbrug, og kun få pletter er overladt til sig selv. Ikke desto mindre spiller naturen...... en stor rolle for både jægerne og for de, der forholder sig kritisk til jagt. Der er stor enighed mellem disse parter om, at naturen er noget, vi skal tage vare på – men når det kommer til, hvilken natur der sigtes til, og hvordan vi skal tage vare på den, skilles vandene. Det skal bemærkes, at vi i...

  2. Natural games

    International Nuclear Information System (INIS)

    Anttila, Jani; Annila, Arto

    2011-01-01

    A course of a game is formulated as a physical process that will consume free energy in the least time. Accordingly, the rate of entropy increase is the payoff function that will subsume all forms of free energy that motivate diverse decisions. Also other concepts of game theory are related to their profound physical counterparts. When the physical portrayal of behavior is mathematically analyzed, the course of a game is found to be inherently unpredictable because each move affects motives in the future. Despite the non-holonomic character of the natural process, the objective of consuming free energy in the least time will direct an extensive-form game toward a Lyapunov-stable point that satisfies the minimax theorem. -- Highlights: → Behavior in the context of game theory is described as a natural process. → The rate of entropy increase, derived from statistical physics of open systems, is identified as the payoff function. → Entropy as the payoff function also clarifies motives of collaboration and subjective nature of decision making. → Evolutionary equation of motion that accounts for the course of a game is inherently unpredictable.

  3. Practical guidance for conducting mediation analysis with multiple mediators using inverse odds ratio weighting.

    Science.gov (United States)

    Nguyen, Quynh C; Osypuk, Theresa L; Schmidt, Nicole M; Glymour, M Maria; Tchetgen Tchetgen, Eric J

    2015-03-01

    Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. A simple and efficient Agrobacterium-mediated procedure for ...

    Indian Academy of Sciences (India)

    Prakash

    , Agrobacterium-mediated plant transformation is the most extensively used method. It exploits the natural ability of Agrobacterium to transform plants to complete its own life cycle (Otoni et al. 2003). Tomato, a member of the Solanaceae family, ...

  5. Chemical and natural stressors combined:

    DEFF Research Database (Denmark)

    Gergs, André; Zenker, Armin; Grimm, Volker

    2013-01-01

    In addition to natural stressors, populations are increasingly exposed to chemical pollutants released into the environment. We experimentally demonstrate the loss of resilience for Daphnia magna populations that are exposed to a combination of natural and chemical stressors even though effects...... vulnerability to the toxicant which acts in a size selective manner. Moreover, population vulnerability to the toxicant increases with predator size and predation intensity whereas indirect trait-mediated interactions via predator kairomones may buffer chemical effects to a certain extent. Our study...... demonstrates that population size can be a poor endpoint for risk assessments of chemicals and that ignoring disturbance interactions can lead to severe underestimation of extinction risk...

  6. Immunologically mediated oral diseases

    OpenAIRE

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  7. Applied mediation analyses

    DEFF Research Database (Denmark)

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart...... disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation...

  8. Implementing general gauge mediation

    International Nuclear Information System (INIS)

    Carpenter, Linda M.; Dine, Michael; Festuccia, Guido; Mason, John D.

    2009-01-01

    Recently there has been much progress in building models of gauge mediation, often with predictions different than those of minimal gauge mediation. Meade, Seiberg, and Shih have characterized the most general spectrum which can arise in gauge-mediated models. We discuss some of the challenges of building models of general gauge mediation, especially the problem of messenger parity and issues connected with R symmetry breaking and CP violation. We build a variety of viable, weakly coupled models which exhibit some or all of the possible low energy parameters.

  9. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9...... complex, but our results did not exclude it completely either. Our attempts to demonstrate the presence of these two subunits in the Mediator complex remain inconclusive primarily due to the lack of proper expression of the tagged versions of the proteins. However, we have paved a way to further...

  10. Direct mediation, duality and unification

    International Nuclear Information System (INIS)

    Abel, Steven; Khoze, Valentin V.

    2008-01-01

    It is well-known that in scenarios with direct gauge mediation of supersymmetry breaking the messenger fields significantly affect the running of Standard Model couplings and introduce Landau poles which are difficult to avoid. Among other things, this appears to remove any possibility of a meaningful unification prediction and is often viewed as a strong argument against direct mediation. We propose two ways that Seiberg duality can circumvent this problem. In the first, which we call 'deflected-unification', the SUSY-breaking hidden sector is a magnetic theory which undergoes a Seiberg duality to an electric phase. Importantly, the electric version has fewer fundamental degrees of freedom coupled to the MSSM compared to the magnetic formulation. This changes the β-functions of the MSSM gauge couplings so as to push their Landau poles above the unification scale. We show that this scenario is realised for recently suggested models of gauge mediation based on a metastable SCQD-type hidden sector directly coupled to MSSM. The second possibility for avoiding Landau poles, which we call 'dual-unification', begins with the observation that, if the mediating fields fall into complete SU(5) multiplets, then the MSSM+messengers exhibits a fake unification at unphysical values of the gauge couplings. We show that, in known examples of electric/magnetic duals, such a fake unification in the magnetic theory reflects a real unification in the electric theory. We therefore propose that the Standard Model could itself be a magnetic dual of some unknown electric theory in which the true unification takes place. This scenario maintains the unification prediction (and unification scale) even in the presence of Landau poles in the magnetic theory below the GUT scale. We further note that this dual realization of grand unification can explain why Nature appears to unify, but the proton does not decay.

  11. Natural relaxation

    Science.gov (United States)

    Marzola, Luca; Raidal, Martti

    2016-11-01

    Motivated by natural inflation, we propose a relaxation mechanism consistent with inflationary cosmology that explains the hierarchy between the electroweak scale and Planck scale. This scenario is based on a selection mechanism that identifies the low-scale dynamics as the one that is screened from UV physics. The scenario also predicts the near-criticality and metastability of the Standard Model (SM) vacuum state, explaining the Higgs boson mass observed at the Large Hadron Collider (LHC). Once Majorana right-handed neutrinos are introduced to provide a viable reheating channel, our framework yields a corresponding mass scale that allows for the seesaw mechanism as well as for standard thermal leptogenesis. We argue that considering singlet scalar dark matter extensions of the proposed scenario could solve the vacuum stability problem and discuss how the cosmological constant problem is possibly addressed.

  12. Natural uranium

    International Nuclear Information System (INIS)

    Ammerich, Marc; Frot, Patricia; Gambini, Denis-Jean; Gauron, Christine; Moureaux, Patrick; Herbelet, Gilbert; Lahaye, Thierry; Pihet, Pascal; Rannou, Alain

    2014-08-01

    This sheet belongs to a collection which relates to the use of radionuclides essentially in unsealed sources. Its goal is to gather on a single document the most relevant information as well as the best prevention practices to be implemented. These sheets are made for the persons in charge of radiation protection: users, radioprotection-skill persons, labor physicians. Each sheet treats of: 1 - the radio-physical and biological properties; 2 - the main uses; 3 - the dosimetric parameters; 4 - the measurement; 5 - the protection means; 6 - the areas delimitation and monitoring; 7 - the personnel classification, training and monitoring; 8 - the effluents and wastes; 9 - the authorization and declaration administrative procedures; 10 - the transport; and 11 - the right conduct to adopt in case of incident or accident. This sheet deals specifically with natural uranium

  13. Natural isotopes

    International Nuclear Information System (INIS)

    Vogel, J.C.

    1986-01-01

    14 C dates between 600 and 900 AD were obtained for early Iron Age sites in Natal, and from 1300 to 1450 AD for rock engraving sites in Bushmanland. Palaeoenvironmental data derived from the dating of samples related to sedimentary and geomorphic features in the central and northern Namib Desert enabled the production of a tentative graph for the changes in humidity in the region over the past 40000 years. These results suggest that relatively humid conditions came to an end in the Namib at ±25000 BP (before present). The increased precision of the SIRA mass spectrometer enabled the remeasurement of 13 C and 18 O in the Cango stalagmite. This data confirmed that the environmental temperatures in the Southern Cape remained constant to within ±1 o C during the past 5500 years. Techniques and applications for environmental isotopes in hydrology were developed to determine the origin and movement of ground water. Isotopic fractionation effects in light elements in nature were investigated. The 15 N/ 14 N ratio in bones of animals and humans increases in proportion to the aridity of the environment. This suggests that 15 N in bone from dated archaeological sites could be used to detect changes in past climatic conditions as naturally formed nitrate minerals are higly soluble and are only preserved in special, very dry environments. The sources and sinks of CO 2 on the South African subcontinent were also determined. The 13 C/ 12 C ratios of air CO 2 obtained suggest that the vegetation provides the major proportion of respired CO 2 . 9 refs., 1 fig

  14. Laccase/Mediator Systems

    NARCIS (Netherlands)

    Hilgers, Roelant; Vincken, Jean Paul; Gruppen, Harry; Kabel, Mirjam A.

    2018-01-01

    Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it

  15. Music, radio and mediatization

    DEFF Research Database (Denmark)

    Michelsen, Morten; Krogh, Mads

    2016-01-01

    Mediatization has become a key concept for understanding the relations between media and other cultural and social fields. Contributing to the discussions related to the concept of mediatization, this article discusses how practices of radio and music(al life) influence each other. We follow Deacon......’s and Stanyer’s advice to supplement the concept of mediatization with ‘a series of additional concepts at lower levels of abstraction’ and suggest, in this respect, the notion of heterogeneous milieus of music–radio. Hereby, we turn away from the all-encompassing perspectives related to the concept...... of mediatization where media as such seem to be ascribed agency. Instead, we consider historical accounts of music–radio in order to address the complex nonlinearity of concrete processes of mediatization as they take place in the multiple meetings between a decentred notion of radio and musical life....

  16. Extended tree-level gauge mediation

    DEFF Research Database (Denmark)

    Monaco, M.; Nardecchia, M.; Romanino, A.

    2011-01-01

    Tree-level gauge mediation (TGM) is a scenario of SUSY breaking in which the tree-level exchange of heavy (possibly GUT) vector fields generates flavor-universal sfermion masses. In this work we extend this framework to the case of E(6) that is the natural extension of the minimal case studied so...... if the gauge group does not contain SU(5). If SUSY breaking is mediated purely by the U(1) generator that commutes with SO(10) we obtain universal sfermion masses and thus can derive the CMSSM boundary conditions in a novel scenario....

  17. Methods for Integrating Moderation and Mediation: A General Analytical Framework Using Moderated Path Analysis

    Science.gov (United States)

    Edwards, Jeffrey R.; Lambert, Lisa Schurer

    2007-01-01

    Studies that combine moderation and mediation are prevalent in basic and applied psychology research. Typically, these studies are framed in terms of moderated mediation or mediated moderation, both of which involve similar analytical approaches. Unfortunately, these approaches have important shortcomings that conceal the nature of the moderated…

  18. Linguagem, saberes e mediação sobrenatural: magia, clerezia e intervenção sobre a natureza no cotidiano e nas representações do Ocidente Medieval = Language, knowledge, and mystical mediation: magic, clergy and intervention on the nature in the quotidian and representations in Medieval West

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Mendes Pereira

    2012-01-01

    Full Text Available A leitura de documentos de origem eclesiástica produzidos durante a Idade Média proporciona a impressão muito clara da presença, no cotidiano dos homens do Ocidente, de inúmeras categorias de mediadores entre o mundo natural e as forças sobrenaturais. De um lado, usando como recurso diversas formas de exercício das artes divinatórias e técnicas de manipulação de elementos da natureza, encontravam-se os magos, especialistas pretensamente dotados de saberes especiais. Às suas ações, o discurso eclesiástico buscou, durante toda a Idade Média, opor o conhecimento e as realizações dos ‘verdadeiros’ agentes do sagrado, aqueles que, organizados em uma ordo à parte do restante da sociedade, a ordo clericorum, desfrutavam do privilégio do acesso à leitura e escrita do latim. O conceito de clerezia com o qual a Igreja Cristã pretendeu qualificar os seus membros trazia implícito um valor cultural que os unificava e distinguia dos primeiros. Entretanto, aos olhos da população, os agentes mágicos, tanto quanto os clérigos, estavam dotados de saberes especializados que lhes facultavam o exercício de poderes estranhos aos comuns dos mortais e lhes possibilitavam controlar forças impessoais capazes de modificar o rumo dos acontecimentos. É nosso propósito discutir a relação entre linguagem, saberes e mediação sobrenatural nas representações correntes sobre agentes mágicos e clérigos na Idade Média.The Reading of documents of ecclesiastical source produced during Middle Ages provides the very clear percept of the presence of various categories of mediators between the natural world and mystical forces, in the daily routine of the western men. On the one hand, there were the wizards, expert supposedly endowed with special knowledge, who used as a resource various forms of exercise of divinatory arts and techniques of manipulation of elements of nature. During Middle Ages the ecclesiastical discourse searched opposing to

  19. General resonance mediation

    International Nuclear Information System (INIS)

    McGarrie, Moritz

    2012-07-01

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for σ(visible → hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  20. Axionic Mirage Mediation

    International Nuclear Information System (INIS)

    Nakamura, Shuntaro; Okumura, Ken-ichi; Yamaguchi, Masahiro

    2008-01-01

    In this talk, we propose a model of mirage mediation, in which Peccei-Quinn symmetry is incorporated. In this axionic mirage mediation, it is shown that the Peccei-Quinn symmetry breaking scale is dynamically determined around 10 10 GeV to 10 12 GeV due to the supersymmetry breaking effects. The problems in the original mirage mediation such as the μ-problem and the moduli problem can be solved simultaneouly. Furthermore, in our model the axino, which is the superpartner of the axion, is the lightest sparticle.

  1. Polyarene mediators for mediated redox flow battery

    Energy Technology Data Exchange (ETDEWEB)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  2. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2004-01-01

    Implementation of new computer-mediated communication (CMC) systems in organizations is a complex socio-technical endeavour, involving the mutual adaptation of technology and organization over time. Drawing on the analytic concept of sensemaking, this paper provides a theoretical perspective...... that deepens our understanding of how organizations appropriate new electronic communication media. The paper analyzes how a group of mediators in a large, multinational company adapted a new web-based CMC technology (a virtual workspace) to the local organizational context (and vice versa) by modifying...... features of the technology, providing ongoing support for users, and promoting appropriate conventions of use. We found that these mediators exerted considerable influence on how the technology was established and used in the organization. The mediators were not neutral facilitators of a well...

  3. Making mediation work.

    Science.gov (United States)

    Arif, Zeba

    2016-10-26

    Mediation can be an effective way of solving conflict between staff members. It signifies a willingness for people to work together to discuss their differences in a constructive way, before going down the official grievance route.

  4. Nature and nature values in organic agriculture

    DEFF Research Database (Denmark)

    Hansen, Lene; Noe, Egon; Højring, Katrine

    2006-01-01

    The relationship between agriculture and nature is a centra issue in the current agricultural debate. Organic farming has ambitions and a special potential in relation to nature. Consideration for nature is part of the guiding principals of organic farming and many organic farmers are committed...... to protecting natural qualities. However, the issue of nature, landscape, and land use is not straightforward. Nature is an ambiguous concept that involves multiple interests and actors reaching far beyond farmers. The Danish research project ......

  5. Understanding Mediation Support

    OpenAIRE

    Lanz, David; Pring, Jamie; von Burg, Corinne; Zeller, Mathias

    2017-01-01

    Recent decades have witnessed increasing institutionalization of mediation support through the establishment of mediation support structures (MSS) within foreign ministries and secretariats of multilateral organizations. This study sheds light on this trend and aims to better understand the emergence, design and development of different MSS. This study analyzes six MSS, namely those established in the United Nations (UN), the Organization for Security and Co-operation in Europe (OSCE), the Eu...

  6. Neurally Mediated Syncope

    OpenAIRE

    Zaqqa, Munir; Massumi, Ali

    2000-01-01

    Neurally mediated syncope is a disorder of the autonomic regulation of postural tone, which results in hypotension, bradycardia, and loss of consciousness. A wide variety of stimuli can trigger this reflex, the most common stimulus being orthostatic stress. Typically, a patient with neurally mediated syncope experiences nausea, lightheadedness, a feeling of warmth, and pallor before abruptly losing consciousness. If the cause of syncope is unclear, a stepwise approach is necessary to arrive a...

  7. Diversity Oriented Synthesis of Natural 2-Arylbenzofuran, Moracin F

    International Nuclear Information System (INIS)

    Yun, So-Ra; Jun, Jong-Gab

    2016-01-01

    Diversity oriented synthesis of natural 2-arylbenzofuran, moracin F (1) has been carried out from the commercially available starting materials using Sonogashira coupling, Suzuki coupling, neutral Al 2 O 3 mediated cyclization, and intramolecular Wittig reaction as key steps.

  8. Hydrological models are mediating models

    Science.gov (United States)

    Babel, L. V.; Karssenberg, D.

    2013-08-01

    Despite the increasing role of models in hydrological research and decision-making processes, only few accounts of the nature and function of models exist in hydrology. Earlier considerations have traditionally been conducted while making a clear distinction between physically-based and conceptual models. A new philosophical account, primarily based on the fields of physics and economics, transcends classes of models and scientific disciplines by considering models as "mediators" between theory and observations. The core of this approach lies in identifying models as (1) being only partially dependent on theory and observations, (2) integrating non-deductive elements in their construction, and (3) carrying the role of instruments of scientific enquiry about both theory and the world. The applicability of this approach to hydrology is evaluated in the present article. Three widely used hydrological models, each showing a different degree of apparent physicality, are confronted to the main characteristics of the "mediating models" concept. We argue that irrespective of their kind, hydrological models depend on both theory and observations, rather than merely on one of these two domains. Their construction is additionally involving a large number of miscellaneous, external ingredients, such as past experiences, model objectives, knowledge and preferences of the modeller, as well as hardware and software resources. We show that hydrological models convey the role of instruments in scientific practice by mediating between theory and the world. It results from these considerations that the traditional distinction between physically-based and conceptual models is necessarily too simplistic and refers at best to the stage at which theory and observations are steering model construction. The large variety of ingredients involved in model construction would deserve closer attention, for being rarely explicitly presented in peer-reviewed literature. We believe that devoting

  9. The Multitalented MEDIATOR25

    Directory of Open Access Journals (Sweden)

    Kemal Kazan

    2017-06-01

    Full Text Available The multi-subunit Mediator complex, which links DNA-bound transcription factors to RNA Pol II during transcription, is an essential regulator of gene expression in all eukaryotes. Individual subunits of the Mediator complex integrate numerous endogenous and exogenous signals. In this paper, diverse regulatory functions performed by MEDIATOR25 (MED25, one of the subunits of the plant Mediator complex are reviewed. MED25 was first identified as a regulator of flowering time and named PHYTOCHROME AND FLOWERING TIME1 (PFT1. Since then, MED25 has been implicated in a range of other plant functions that vary from hormone signaling (JA, ABA, ethylene, and IAA to biotic and abiotic stress tolerance and plant development. MED25 physically interacts with transcriptional activators (e.g., AP2/ERFs, MYCs, and ARFs, repressors (e.g., JAZs and Aux/IAAs, and other Mediator subunits (MED13 and MED16. In addition, various genetic and epigenetic interactions involving MED25 have been reported. These features make MED25 one of the most multifunctional Mediator subunits and provide new insights into the transcriptional control of gene expression in plants.

  10. DISPUTE RESOLUTION AND MEDIATION ON CAPITAL MARKET

    Directory of Open Access Journals (Sweden)

    CRISTIAN GHEORGHE

    2011-04-01

    Full Text Available Capital Market is usually depicted as a place for experts, for people with high trading skills. This is a half truth. There are entities established and functioning under strict scrutiny of Romanian National Securities Commission (RNSC, in compliance with Capital Market Law and regulations. There are also the investors, in many cases individuals involved in shares/financial instruments trade. In both cases disputes can rise. Disputes are inevitable a part of human interaction, hence the need for dispute resolution. First option is the judicial court system. Alternative dispute resolution comprises arbitration and mediation. Arbitration is an alternative choice to provide simpler, speedier and more accessible justice than ordinary courts as well as expertise in matters that are technical in nature and require special knowledge to adjudicate upon. Capital Market environment provides an institutional arbitration court for all participants, including investors. In many cases the agreement executed between participants under RNSC scrutiny The other option for settling disputes outside the court is mediation. Mediation can provide a much cheaper and quick extrajudicial resolution of disputes in commercial matters without time consuming procedures and rigid rules. Agreements resulting from mediation are more likely to be complied with voluntarily and are more likely to foster the commercial relationship between the parties. The interaction between investors and brokerage houses is based on investment services agreement concluded by parties. This is the usual framework for disputes between parties and the usual “landscape” for mediation on capital market.

  11. Analysis of multiparty mediation processes

    NARCIS (Netherlands)

    Vuković, Siniša

    2013-01-01

    Crucial challenges for multiparty mediation processes include the achievement of adequate cooperation among the mediators and consequent coordination of their activities in the mediation process. Existing literature goes only as far as to make it clear that successful mediation requires necessary

  12. Place attachment and natural environmental risk

    DEFF Research Database (Denmark)

    Bonaiuto, Marino; Alves, Susana; De Dominicis, Stefano

    2016-01-01

    Little is known about place attachment affecting natural environmental risk perception and coping. A systematic search of social science databases revealed 31 works (1996–2016) directly addressing place attachment in relation to different types of natural hazard risks (e.g., seismic, volcanic, etc.......). Across different contexts, the research shows: (a) positive and/or negative relationships between place attachment and natural environmental risk perception; (b) positive and/or negative relationships between place attachment and risk coping; and (c) mediating and moderating relationships. In particular......, results show that: (a) highly attached individuals perceive natural environmental risks but underestimate their potential effects; (b) highly attached individuals are unwilling to relocate when facing natural environmental risks and more likely to return to risky areas after a natural environmental...

  13. Mediation: The Wise Advocacy

    Directory of Open Access Journals (Sweden)

    Towseef Ahmad

    2016-01-01

    Full Text Available AbstractAdversarial litigation is not the only means of resolving disputes and settling of claims. There are various options. Alternative means of dispute resolution can save money and time, and can help to anchor and resolve the dispute while exploring valuable good offices, amicable approaches and facilitation. Mediation, as used in law, is a process of managing negotiation by a neutral third party in the form of Alternative Dispute Resolution (ADR, as a convenient way of resolving disputes between two or more parties with speediation processes. On the sidelines typically, a neutral third party, the mediator assists the parties to negotiate a settlement. The term “mediation” broadly refers to any instance in which a neutral third party helps others to reach an amicable and mutually acceptable agreement. More specifically, mediation has a structure, timetable and dynamic approaches that “ordinary” negotiations usually lack. The process helps the parties to flourish the healthy ideas which are different and distinct from the legal rights in a Court of law. It is well known in International Law also and disputants can submit their disputes to mediation in a variety of matters such as commercial, legal, diplomatic, workplace, community and family matters, which assumes a great significance and it is bricolaged within the framework of this article.Keywords: Adversarial, Litigation, Mediation, Negotiation and Amicable.

  14. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    , respectively. The paper thus takes on aesthetics and the social in a manner closely related to a core argument of STS - namely that the scientific fact, and the social processes of constructing, distributing, and using that fact, are co-constructed (Callon, 1986; Latour, 1993). The paper thus contributes......, it is an important ambition of this paper to go into a methodological discussion of how "that which effectively happens" can be approached. To this end, the paper will combine Hennion's term of the "mediator" with John Laws methodological term of "method assemblages". Method assemblages is a suggested as a way...... of handling multiple, fluid realities with multiple, fluid methods. Empirically, the paper works with mediation in fashion - that is efforts the active shaping of relations between producer and consumer through communication, marketing and PR. Fashion mediation is by no means simple, but organise complex...

  15. Immunologically mediated oral diseases.

    Science.gov (United States)

    Jimson, Sudha; Balachader, N; Anita, N; Babu, R

    2015-04-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  16. Immunologically mediated oral diseases

    Directory of Open Access Journals (Sweden)

    Sudha Jimson

    2015-01-01

    Full Text Available Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  17. Mediation and Legal Assistance

    Directory of Open Access Journals (Sweden)

    Larisa Zaitseva

    2014-01-01

    Full Text Available The development of alternative dispute resolution procedures raises a number of new problems and questions for jurisprudence and legal practice. Many of these are closely related to the implementation of mediation procedures. Significant attention has been paid in the legal literature to the need for mediators’ legal education. Nowadays a professional lawyer usually performs the functions of a mediator. Nevertheless, in some countries the competence of mediators can be limited. In fact, such persons may be prohibited from providing any legal assistance to the parties. A direct prohibition of this kind exists in Russian legislation. To what degree is this prohibition realistic and reasonable? Different countries enjoy different approaches to the possibility of providing disputing parties with a mediator’s legal assistance in addressing issues requiring legal advice or in the drafting of legal documents. Different approaches to this issue have appeared for various reasons. The absence of consensus is caused by a contradiction between the principle of mediator neutrality in the conflict resolution process and the goals of dispute settlement in which a legally competent intermediary is involved. To ensure the effectiveness of the mediation process, legislators should seek out more flexible ways of regulating procedure. Mandatory regulation itself contradicts the spirit of ‘semi-formal’ alternative (extrajudicial methods for conflict resolution. As such, the presence of direct prohibitions or severe restrictions may not only become challenging in the performance of law but such peremptory norms can also make mediation unattractive and ineffective for some particular types of dispute, such as labor disputes. The principle of preserving a mediator’s neutrality is possible if exercised within the framework of a balanced approach to reasonable limits and discretionary rules for the provision of certain types of legal assistance to disputing

  18. Mediated intimacy in families

    DEFF Research Database (Denmark)

    Stougaard, Malthe Kirkhoff

    2006-01-01

    Mediating intimacy between children and their parents is still limited investigated and at the same time, we find that, emerging technologies are about to change and affect the way we interact with each other. In this paper, we report from an empirical study where we investigated the social...... with other types of intimate relations such as strong-tie intimacy (couples cohabiting). However, we also identified several issues of intimacy unique to the special relation between children and their parents. These unique acts of intimacy propose challenges when designing technologies for mediated intimacy...

  19. Focus point gauge mediation in product group unification

    International Nuclear Information System (INIS)

    Brümmer, Felix; Ibe, Masahiro; Yanagida, Tsutomu T.

    2013-01-01

    In certain models of gauge-mediated supersymmetry breaking with messenger fields in incomplete GUT multiplets, the radiative corrections to the Higgs potential cancel out during renormalization group running. This allows for relatively heavy superpartners and for a 125 GeV Higgs while the fine-tuning remains modest. In this Letter, we show that such gauge mediation models with “focus point” behaviour can be naturally embedded into a model of SU(5)×U(3) product group unification

  20. Focus point gauge mediation in product group unification

    International Nuclear Information System (INIS)

    Bruemmer, Felix; Ibe, Masahiro; Tokyo Univ., Kashiwa; Yanagida, Tsutomu T.

    2013-03-01

    In certain models of gauge-mediated supersymmetry breaking with messenger fields in incomplete GUT multiplets, the radiative corrections to the Higgs potential cancel out during renormalization group running. This allows for relatively heavy superpartners and for a 125 GeV Higgs while the ne-tuning remains modest. In this paper, we show that such gauge mediation models with ''focus point'' behaviour can be naturally embedded into a model of SU(5) x U(3) product group unification.

  1. Deflected Mirage Mediation: A Framework for Generalized Supersymmetry Breaking

    International Nuclear Information System (INIS)

    Kim, Ian-Woo

    2008-01-01

    We present a model of supersymmetry breaking in which the contributions from gravity/modulus, anomaly, and gauge mediation are all comparable. We term this scenario 'deflected mirage mediation', which is a generalization of the KKLT-motivated mirage mediation scenario to include gauge mediated contributions. These contributions deflect the gaugino mass unification scale and alter the pattern of soft parameters at low energies. Competitive gauge-mediated terms can naturally appear within phenomenological models based on the KKLT setup by the stabilization of the gauge singlet field responsible for the masses of the messenger fields. We analyze the renormalization group evolution of the supersymmetry breaking terms and the resulting low energy mass spectra.

  2. Mediation skills for conflict resolution in nursing education.

    Science.gov (United States)

    Cheng, Fung Kei

    2015-07-01

    Encountering conflicts among family members in hospital produces burnout among nurses, implying a need for alternative dispute resolution training. However, current nursing education pays more attention to counselling skills training than to mediation. The present report examines the fundamental concepts of mediation, including its nature, basic assumptions and values, and compares those with counselling. Its implications may open a discussion on enhancing contemporary nursing education by providing mediation training in the workplace to nurses so that they can deal more effectively with disputes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Non-minimal gauge mediation and moduli stabilization

    International Nuclear Information System (INIS)

    Jelinski, T.; Lalak, Z.; Pawelczyk, J.

    2010-01-01

    In this Letter we consider U(1) A -gauged Polonyi model with two spurions coupled to a twisted closed string modulus. This offers a consistent setup for metastable SUSY breakdown which allows for moduli stabilization and naturally leads to gauge or hybrid gauge/gravitational mediation mechanism. Due to the presence of the second spurion one can arrange for a solution of the μ and B μ problems in a version of modified Giudice-Masiero mechanism, which works both in the limit of pure gauge mediation and in the mixed regime of hybrid mediation.

  4. Cultural mediation in museums

    Directory of Open Access Journals (Sweden)

    Gherghina Boda

    2017-12-01

    Full Text Available If we perceive the museum not only as a place of storing and conserving the patrimony, but also of transmitting it, then we can also see it as a mediator through which cultures can become collective patrimony. Tightly connected to patrimonial appropriation, mediation appears from this perspective as a process and not an end, as it manifests itself in animation, communication and making knowledge popular in relation to a precise patrimony. That is why we can see cultural mediation as a transmission, as a transformation, as an action or social project which aims at creating social bonds, the museum thus being not only a place of meeting for the public with the objects exposed, but also as a place of meeting between different cultures. Thus, cultural mediation presents itself as the most efficient means for access to culture of all categories of the public, situated as the crossroads of culture, continuous education and entertainment and is inscribed in the field of informal education.

  5. Bradykinin-mediated angioedema.

    Science.gov (United States)

    Obtułowicz, Krystyna

    2016-01-01

    Angioedema and urticaria often constitute a challenge in daily clinical practice. They may either co- -occur or present as independent conditions. They are characterized by a complex pathomechanism, and their symptoms may be triggered by diverse factors. These differences are crucial for developing a successful treatment regimen. Both conditions may have an allergic origin (immunoglobulin [Ig] E and non-IgE-related), usually induced by histamine, or a nonallergic one, such as bradykinin-mediated angioedema in patients with C1 inhibitor (C1-INH) deficiency or angioedema induced by certain drugs (eg, angiotensin-converting enzyme inhibitors). Currently, we distinguish 5 types of nonallergic angioedema: hereditary angioedema (HAE) due to C1-INH deficiency, acquired angioedema (AAE), and angioedema induced by the renin-angiotensin-aldosterone system, all of which are mediated by bradykinin, as well as pseudoallergic angioedema and idiopathic angioedema. Bradykinin-mediated angioedema (eg, laryngeal angioedema) may be life-threatening because of resistance to corticosteroids and antihistamine drugs. C1-INH concentrates are the drugs of choice in the treatment of HAE and AAE. In recent years, some new drugs have been introduced in the treatment of bradykinin-mediated angioedema, such as bradykinin B2-receptor antagonist, icatibant, and kallikrein inhibitor, ecallantide, which allow to improve treatment outcomes.

  6. The Bensberg Mediation Model

    Directory of Open Access Journals (Sweden)

    Raluca - Marilena Mihalcioiu

    2011-05-01

    Full Text Available The basis of the conflict through the mediation represents the objectives and procedures ofmediation, mediation of a conflict. The conflict will not be disclosed to others, but the parties will be creditedthe authority to resolve the conflict, the conflict among themselves with the help of a mediator. The disputeshould be resolved by the parties with help of a third party. The parties in conflict (it may be several personsare jointly responsible for the solution. They seek together a way that leads to long-term settlement of theconflict. The assumption of responsibility in this process strengthens the confidence and the importance oftheir decision. Important is that losers usually have no peace, because they are out for revenge. Winners don’tneed peace. If both parties lose, remains disappointing, with the understanding of which the conflict isresolved, will understand each other better developed. Reconciliation is therefore a longer-term goal.Conflicts also help to clarify roles. The paper presents Bensberg Model of Mediation, because this isdeveloped as a win win solution and his possible implementation in Romanian schools.

  7. Den sundhedsfremmende mediator

    DEFF Research Database (Denmark)

    Læssøe, Jeppe

    2009-01-01

    mediering samt mellem forskellige mediator-roller og tilhørsforhold. Det er også vigtigt at være bevidst om de centrale kvaliteter, risici og dilemmaer, som mediering indebærer i forhold til involvering af borgerne. Denne artikel rummer et bud på en sådan nuanceret begrebsliggørelse og refleksion, relateret...

  8. Expanding mediation theory

    NARCIS (Netherlands)

    Verbeek, Peter P.C.C.

    2012-01-01

    In his article In Between Us, Yoni van den Eede expands existing theories of mediation into the realm of the social and the political, focusing on the notions of opacity and transparency. His approach is rich and promising, but two pitfalls should be avoided. First, his concept of ‘in-between’ runs

  9. Nature and nature values in organic agriculture

    DEFF Research Database (Denmark)

    Hansen, Lene; Noe, Egon; Højring, Katrine

    2006-01-01

    The relationship between agriculture and nature is a centra issue in the current agricultural debate. Organic farming has ambitions and a special potential in relation to nature. Consideration for nature is part of the guiding principals of organic farming and many organic farmers are committed t...

  10. SUSY breaking mediation by throat fields

    International Nuclear Information System (INIS)

    Bruemmer, F.; Hebecker, A.; Trapletti, M.

    2006-01-01

    We investigate, in the general framework of KKLT, the mediation of supersymmetry breaking by fields propagating in the strongly warped region of the compactification manifold ('throat fields'). Such fields can couple both to the supersymmetry breaking sector at the IR end of the throat and to the visible sector at the UV end. We model the supersymmetry breaking sector by a chiral superfield which develops an F term vacuum expectation value (also responsible for the uplift). It turns out that the mediation effect of vector multiplets propagating in the throat can compete with modulus-anomaly mediation. Moreover, such vector fields are naturally present as the gauge fields arising from isometries of the throat (most notably the SO(4) isometry of the Klebanov-Strassler solution). Their mediation effect is important in spite of their large 4d mass. The latter is due to the breaking of the throat isometry by the compact manifold at the UV end of the throat. The contribution from heavy chiral superfields is found to be subdominant

  11. SPECIAL ISSUES REGARDING THE MEDIATION PROCESS IN THE COMMERCIAL FIELD

    Directory of Open Access Journals (Sweden)

    SEPTIMIU STOICA

    2012-05-01

    Full Text Available The purpose of the research subject to this paper is to find proper solutions for the increase of the volume and efficiency in the field of commercial mediation. Starting from practical remarks, after an analysis of the substance, a new concept is suggested to be included and put into operation, namely the special commercial mediation, and a plead is made for its use in the current activity of alternative dispute resolution. The first major objective of this paper is to demonstrate once again the need and utility of mediation in the commercial field, insisting though on its remarkable specific nature. The second objective is, starting from the outlined differences between the commercial mediation and the classical mediation, to define and to conceptualize the special commercial mediation, as a separate branch of mediation. The third objective of this paper is to draw the regime of the newly defined category of commercial mediation from a regulatory point of view, of the implementation structure and techniques as foreseen.

  12. Natural gas trends

    International Nuclear Information System (INIS)

    Anderson, A.

    1991-01-01

    This book provides data on many facets of the natural gas industry. Topics include: Canadian, Mexican; US natural gas reserves and production; Mexican and US natural gas consumption; market conditions for natural gas in the US; and Canadian natural gas exports

  13. Current Directions in Mediation Analysis

    Science.gov (United States)

    MacKinnon, David P.; Fairchild, Amanda J.

    2010-01-01

    Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables. PMID:20157637

  14. [Mediation in schools].

    Science.gov (United States)

    Mickley, Angela

    2006-01-01

    In this article the guiding questions concern the objectives and effectiveness of introducing mediation into an existing school culture of dominance, competition and selection. In addition the necessity will be shown of combining conflict resolution with organisational development and the introduction of a consensual ethics and behaviour code to attain sustainable results in creating a constructive and healthy school environment. Given scarce resources and little time the decisive role of artistic methods will be looked at in providing young people with flexible methods of expressing and negotiating their interests in a changing environment of values and power structures. Some aspects of the development of nonviolent communication, conflict resolution and mediation methods in schools in Germany will be focused on with special emphasis on the type of intervention used and its long term sustainable effects.

  15. Church mediation - een vak apart

    NARCIS (Netherlands)

    Annelies Klinefelter; dr Hans A.J. Jonker

    2009-01-01

    Welke rol kan mediation in de kerk spelen in de diverse geledingen en specifieke activiteiten? In dit artikel wordt ingegaan op kerkelijke conflicten, gelaagdheid in church mediation, en specifieke dilemma's van church mediation. Daarnaast komen enkele benaderingen aan bod zoals: helende

  16. Neurally-mediated sincope.

    Science.gov (United States)

    Can, I; Cytron, J; Jhanjee, R; Nguyen, J; Benditt, D G

    2009-08-01

    Syncope is a syndrome characterized by a relatively sudden, temporary and self-terminating loss of consciousness; the causes may vary, but they have in common a temporary inadequacy of cerebral nutrient flow, usually due to a fall in systemic arterial pressure. However, while syncope is a common problem, it is only one explanation for episodic transient loss of consciousness (TLOC). Consequently, diagnostic evaluation should start with a broad consideration of real or seemingly real TLOC. Among those patients in whom TLOC is deemed to be due to ''true syncope'', the focus may then reasonably turn to assessing the various possible causes; in this regard, the neurally-mediated syncope syndromes are among the most frequently encountered. There are three common variations: vasovagal syncope (often termed the ''common'' faint), carotid sinus syndrome, and the so-called ''situational faints''. Defining whether the cause is due to a neurally-mediated reflex relies heavily on careful history taking and selected testing (e.g., tilt-test, carotid massage). These steps are important. Despite the fact that neurally-mediated faints are usually relatively benign from a mortality perspective, they are nevertheless only infrequently an isolated event; neurally-mediated syncope tends to recur, and physical injury resulting from falls or accidents, diminished quality-of-life, and possible restriction from employment or avocation are real concerns. Consequently, defining the specific form and developing an effective treatment strategy are crucial. In every case the goal should be to determine the cause of syncope with sufficient confidence to provide patients and family members with a reliable assessment of prognosis, recurrence risk, and treatment options.

  17. Teachers as mediators

    DEFF Research Database (Denmark)

    Dorf, Hans; Kelly, Peter; Hohmann, Ulrike

    2012-01-01

    Within the context of lower secondary English teaching in South West England, this study identifies in broad terms the competing goals between which English teachers mediate and the explicit and hidden tensions that result. To understand the interactions of competing goals, teachers’ goal...... and cultural influences on practice. Yet the teachers observed moved smoothly between goal-oriented behaviours in a continuous and comfortable style, easily and without reflecting any tensions between them. Thus, this article elaborates an account of situated English teaching....

  18. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  19. Lopsided Gauge Mediation

    CERN Document Server

    De Simone, Andrea; Giudice, Gian Francesco; Pappadopulo, Duccio; Rattazzi, Riccardo

    2011-01-01

    It has been recently pointed out that the unavoidable tuning among supersymmetric parameters required to raise the Higgs boson mass beyond its experimental limit opens up new avenues for dealing with the so called $\\mu$-$B_\\mu$ problem of gauge mediation. In fact, it allows for accommodating, with no further parameter tuning, large values of $B_\\mu$ and of the other Higgs-sector soft masses, as predicted in models where both $\\mu$ and $B_\\mu$ are generated at one-loop order. This class of models, called Lopsided Gauge Mediation, offers an interesting alternative to conventional gauge mediation and is characterized by a strikingly different phenomenology, with light higgsinos, very large Higgs pseudoscalar mass, and moderately light sleptons. We discuss general parametric relations involving the fine-tuning of the model and various observables such as the chargino mass and the value of $\\tan\\beta$. We build an explicit model and we study the constraints coming from LEP and Tevatron. We show that in spite of ne...

  20. Natural Colorants: Food Colorants from Natural Sources.

    Science.gov (United States)

    Sigurdson, Gregory T; Tang, Peipei; Giusti, M Mónica

    2017-02-28

    The color of food is often associated with the flavor, safety, and nutritional value of the product. Synthetic food colorants have been used because of their high stability and low cost. However, consumer perception and demand have driven the replacement of synthetic colorants with naturally derived alternatives. Natural pigment applications can be limited by lower stability, weaker tinctorial strength, interactions with food ingredients, and inability to match desired hues. Therefore, no single naturally derived colorant can serve as a universal alternative for a specified synthetic colorant in all applications. This review summarizes major environmental and biological sources for natural colorants as well as nature-identical counterparts. Chemical characteristics of prevalent pigments, including anthocyanins, carotenoids, betalains, and chlorophylls, are described. The possible applications and hues (warm, cool, and achromatic) of currently used natural pigments, such as anthocyanins as red and blue colorants, and possible future alternatives, such as purple violacein and red pyranoanthocyanins, are also discussed.

  1. Regularities, Natural Patterns and Laws of Nature

    Directory of Open Access Journals (Sweden)

    Stathis Psillos

    2014-02-01

    Full Text Available  The goal of this paper is to sketch an empiricist metaphysics of laws of nature. The key idea is that there are regularities without regularity-enforcers. Differently put, there are natural laws without law-makers of a distinct metaphysical kind. This sketch will rely on the concept of a natural pattern and more significantly on the existence of a network of natural patterns in nature. The relation between a regularity and a pattern will be analysed in terms of mereology.  Here is the road map. In section 2, I will briefly discuss the relation between empiricism and metaphysics, aiming to show that an empiricist metaphysics is possible. In section 3, I will offer arguments against stronger metaphysical views of laws. Then, in section 4 I will motivate nomic objectivism. In section 5, I will address the question ‘what is a regularity?’ and will develop a novel answer to it, based on the notion of a natural pattern. In section 6, I will raise the question: ‘what is a law of nature?’, the answer to which will be: a law of nature is a regularity that is characterised by the unity of a natural pattern.

  2. G-computation demonstration in causal mediation analysis.

    Science.gov (United States)

    Wang, Aolin; Arah, Onyebuchi A

    2015-10-01

    Recent work has considerably advanced the definition, identification and estimation of controlled direct, and natural direct and indirect effects in causal mediation analysis. Despite the various estimation methods and statistical routines being developed, a unified approach for effect estimation under different effect decomposition scenarios is still needed for epidemiologic research. G-computation offers such unification and has been used for total effect and joint controlled direct effect estimation settings, involving different types of exposure and outcome variables. In this study, we demonstrate the utility of parametric g-computation in estimating various components of the total effect, including (1) natural direct and indirect effects, (2) standard and stochastic controlled direct effects, and (3) reference and mediated interaction effects, using Monte Carlo simulations in standard statistical software. For each study subject, we estimated their nested potential outcomes corresponding to the (mediated) effects of an intervention on the exposure wherein the mediator was allowed to attain the value it would have under a possible counterfactual exposure intervention, under a pre-specified distribution of the mediator independent of any causes, or under a fixed controlled value. A final regression of the potential outcome on the exposure intervention variable was used to compute point estimates and bootstrap was used to obtain confidence intervals. Through contrasting different potential outcomes, this analytical framework provides an intuitive way of estimating effects under the recently introduced 3- and 4-way effect decomposition. This framework can be extended to complex multivariable and longitudinal mediation settings.

  3. G-computation demonstration in causal mediation analysis

    International Nuclear Information System (INIS)

    Wang, Aolin; Arah, Onyebuchi A.

    2015-01-01

    Recent work has considerably advanced the definition, identification and estimation of controlled direct, and natural direct and indirect effects in causal mediation analysis. Despite the various estimation methods and statistical routines being developed, a unified approach for effect estimation under different effect decomposition scenarios is still needed for epidemiologic research. G-computation offers such unification and has been used for total effect and joint controlled direct effect estimation settings, involving different types of exposure and outcome variables. In this study, we demonstrate the utility of parametric g-computation in estimating various components of the total effect, including (1) natural direct and indirect effects, (2) standard and stochastic controlled direct effects, and (3) reference and mediated interaction effects, using Monte Carlo simulations in standard statistical software. For each study subject, we estimated their nested potential outcomes corresponding to the (mediated) effects of an intervention on the exposure wherein the mediator was allowed to attain the value it would have under a possible counterfactual exposure intervention, under a pre-specified distribution of the mediator independent of any causes, or under a fixed controlled value. A final regression of the potential outcome on the exposure intervention variable was used to compute point estimates and bootstrap was used to obtain confidence intervals. Through contrasting different potential outcomes, this analytical framework provides an intuitive way of estimating effects under the recently introduced 3- and 4-way effect decomposition. This framework can be extended to complex multivariable and longitudinal mediation settings

  4. Incorporating nonlinearity into mediation analyses.

    Science.gov (United States)

    Knafl, George J; Knafl, Kathleen A; Grey, Margaret; Dixon, Jane; Deatrick, Janet A; Gallo, Agatha M

    2017-03-21

    Mediation is an important issue considered in the behavioral, medical, and social sciences. It addresses situations where the effect of a predictor variable X on an outcome variable Y is explained to some extent by an intervening, mediator variable M. Methods for addressing mediation have been available for some time. While these methods continue to undergo refinement, the relationships underlying mediation are commonly treated as linear in the outcome Y, the predictor X, and the mediator M. These relationships, however, can be nonlinear. Methods are needed for assessing when mediation relationships can be treated as linear and for estimating them when they are nonlinear. Existing adaptive regression methods based on fractional polynomials are extended here to address nonlinearity in mediation relationships, but assuming those relationships are monotonic as would be consistent with theories about directionality of such relationships. Example monotonic mediation analyses are provided assessing linear and monotonic mediation of the effect of family functioning (X) on a child's adaptation (Y) to a chronic condition by the difficulty (M) for the family in managing the child's condition. Example moderated monotonic mediation and simulation analyses are also presented. Adaptive methods provide an effective way to incorporate possibly nonlinear monotonicity into mediation relationships.

  5. Incorporating nonlinearity into mediation analyses

    Directory of Open Access Journals (Sweden)

    George J. Knafl

    2017-03-01

    Full Text Available Abstract Background Mediation is an important issue considered in the behavioral, medical, and social sciences. It addresses situations where the effect of a predictor variable X on an outcome variable Y is explained to some extent by an intervening, mediator variable M. Methods for addressing mediation have been available for some time. While these methods continue to undergo refinement, the relationships underlying mediation are commonly treated as linear in the outcome Y, the predictor X, and the mediator M. These relationships, however, can be nonlinear. Methods are needed for assessing when mediation relationships can be treated as linear and for estimating them when they are nonlinear. Methods Existing adaptive regression methods based on fractional polynomials are extended here to address nonlinearity in mediation relationships, but assuming those relationships are monotonic as would be consistent with theories about directionality of such relationships. Results Example monotonic mediation analyses are provided assessing linear and monotonic mediation of the effect of family functioning (X on a child’s adaptation (Y to a chronic condition by the difficulty (M for the family in managing the child's condition. Example moderated monotonic mediation and simulation analyses are also presented. Conclusions Adaptive methods provide an effective way to incorporate possibly nonlinear monotonicity into mediation relationships.

  6. What carries a mediation process? Configural analysis of mediation.

    Science.gov (United States)

    von Eye, Alexander; Mun, Eun Young; Mair, Patrick

    2009-09-01

    Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

  7. Agrobacterium-mediated transformation: rice transformation.

    Science.gov (United States)

    Slamet-Loedin, Inez H; Chadha-Mohanty, Prabhjit; Torrizo, Lina

    2014-01-01

    Agrobacterium is a common soil bacterium with natural capacity for trans-kingdom transfer of genetic information by transferring its T-DNA into the eukaryotic genome. In agricultural plant biotechnology, combination of non-phytopathogenic strain of Agrobacterium tumefaciens with modified T-DNA and vir-genes in a binary vector system is the most widely utilized system for genetic improvement in diverse plant species and for gene function validation. Here we have described a highly efficient A. tumefaciens-mediated transformation system for indica and japonica rice cultivars based on an immature embryo system.

  8. What is 'Natural'in Natural Selection?

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 5. What is 'Natural' in Natural Selection? Abhijeet S Bardapurkar. Classroom Volume 18 Issue 5 May 2013 pp 475-482. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/018/05/0475-0482. Keywords.

  9. Natural and near natural tropical forest values

    Science.gov (United States)

    Daniel H. Henning

    2011-01-01

    This paper identifies and describes some of the values associated with tropical rain forests in their natural and near-natural conditions. Tropical rain forests are moist forests in the humid tropics where temperature and rainfall are high and the dry season is short. These closed (non-logged) and broad-leaved forests are a global resource. Located almost entirely in...

  10. Learning from nature: Nature-inspired algorithms

    DEFF Research Database (Denmark)

    Albeanu, Grigore; Madsen, Henrik; Popentiu-Vladicescu, Florin

    2016-01-01

    During last decade, the nature has inspired researchers to develop new algorithms. The largest collection of nature-inspired algorithms is biology-inspired: swarm intelligence (particle swarm optimization, ant colony optimization, cuckoo search, bees' algorithm, bat algorithm, firefly algorithm etc...

  11. Three Sorts of Naturalism

    DEFF Research Database (Denmark)

    Fink, Hans

    2006-01-01

    In "Two sorts of Naturalism" John McDowell is sketching his own sort of naturalism in ethics as an alternative to "bald naturalism". In this paper I distinguish materialist, idealist and absolute conceptions of nature and of naturalism in order to provide a framework for a clearer understanding...... of what McDowell's own naturalism amounts to. I argue that nothing short of an absolute naturalism will do for a number of McDowell's own purposes, but that it is far from obvious that this is his position. If he directly denies that it is, he seems to be left with some rather awkward choices....

  12. Three Sorts of Naturalism

    OpenAIRE

    Fink, Hans

    2006-01-01

    In "Two sorts of Naturalism" John McDowell is sketching his own sort of naturalism in ethics as an alternative to "bald naturalism". In this paper I distinguish materialist, idealist and absolute conceptions of nature and of naturalism in order to provide a framework for a clearer understanding of what McDowell's own naturalism amounts to. I argue that nothing short of an absolute naturalism will do for a number of McDowell's own purposes, but that it is far from obvious that this is his posi...

  13. Translation as cultural mediator

    Directory of Open Access Journals (Sweden)

    Roxana Petcu

    2009-01-01

    Full Text Available The aim of this paper is to analyze the role that translation plays as cultural mediator, as it already widely accepted that translation involves not just two languages, but two cultures, two worlds that are brought into close contact with each other. Obviously, between the two cultures, the two worlds that translation compares and contrasts there are both similarities and dissimilarities. What is of interest to us is the way in which dissimilarities should be approached in the process of translation, whether they should be domesticated or foreignized as Venuti put it, whether the reader should be brought closer to the text or the text closer to the reader.

  14. Holographic Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Benini, Francesco; /Princeton U.; Dymarsky, Anatoly; /Stanford U., ITP; Franco, Sebastian; /Santa Barbara, KITP; Kachru, Shamit; Simic, Dusan; /Stanford U., ITP /SLAC; Verlinde, Herman; /Princeton, Inst. Advanced Study

    2009-06-19

    We discuss gravitational backgrounds where supersymmetry is broken at the end of a warped throat, and the SUSY-breaking is transmitted to the Standard Model via gauginos which live in (part of) the bulk of the throat geometry. We find that the leading effect arises from splittings of certain 'messenger mesons,' which are adjoint KK-modes of the D-branes supporting the Standard Model gauge group. This picture is a gravity dual of a strongly coupled field theory where SUSY is broken in a hidden sector and transmitted to the Standard Model via a relative of semi-direct gauge mediation.

  15. Urban Songlines as Mediator

    DEFF Research Database (Denmark)

    Corlin, Anne

    2016-01-01

    The aim of this paper is to present an investigation of the method The Urban Songlines Book and how it works as a mediator for mapping the experienced space. The method contains a combination of aerial maps, photographs, and interviews as a way to understand the respondent´s use, relations...... and experiences of their neighborhood and the city. Through a presentation of the origin of the method, a description of the conducted study, and an analysis of the process in relation to theories about participatory design, social design, ANT and architectural sociology, the paper reveals how this method...

  16. 45 CFR 16.18 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 16.18 Section 16.18 Public Welfare... BOARD § 16.18 Mediation. (a) In cases pending before the Board. If the Board decides that mediation... mediation techniques and will provide or assist in selecting a mediator. The mediator may take any steps...

  17. Hypothesis test of mediation effect in causal mediation model with high-dimensional continuous mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Pan, Wen-Chi

    2016-06-01

    Causal mediation modeling has become a popular approach for studying the effect of an exposure on an outcome through a mediator. However, current methods are not applicable to the setting with a large number of mediators. We propose a testing procedure for mediation effects of high-dimensional continuous mediators. We characterize the marginal mediation effect, the multivariate component-wise mediation effects, and the L2 norm of the component-wise effects, and develop a Monte-Carlo procedure for evaluating their statistical significance. To accommodate the setting with a large number of mediators and a small sample size, we further propose a transformation model using the spectral decomposition. Under the transformation model, mediation effects can be estimated using a series of regression models with a univariate transformed mediator, and examined by our proposed testing procedure. Extensive simulation studies are conducted to assess the performance of our methods for continuous and dichotomous outcomes. We apply the methods to analyze genomic data investigating the effect of microRNA miR-223 on a dichotomous survival status of patients with glioblastoma multiforme (GBM). We identify nine gene ontology sets with expression values that significantly mediate the effect of miR-223 on GBM survival. © 2015, The International Biometric Society.

  18. A fragrant neighborhood: Volatile mediated bacterial interactions in soil

    NARCIS (Netherlands)

    Schulz-Bohm, K.; Zweers, H.; Boer, de W.; Garbeva, P.

    2015-01-01

    There is increasing evidence that volatile organic compounds play essential roles in communication and competition between soil microorganisms. Here we assessed volatile-mediated interactions of a synthetic microbial community in a model system that mimics the natural conditions in the heterogeneous

  19. SPSS and SAS programming for the testing of mediation models.

    Science.gov (United States)

    Dudley, William N; Benuzillo, Jose G; Carrico, Mineh S

    2004-01-01

    Mediation modeling can explain the nature of the relation among three or more variables. In addition, it can be used to show how a variable mediates the relation between levels of intervention and outcome. The Sobel test, developed in 1990, provides a statistical method for determining the influence of a mediator on an intervention or outcome. Although interactive Web-based and stand-alone methods exist for computing the Sobel test, SPSS and SAS programs that automatically run the required regression analyses and computations increase the accessibility of mediation modeling to nursing researchers. To illustrate the utility of the Sobel test and to make this programming available to the Nursing Research audience in both SAS and SPSS. The history, logic, and technical aspects of mediation testing are introduced. The syntax files sobel.sps and sobel.sas, created to automate the computation of the regression analysis and test statistic, are available from the corresponding author. The reported programming allows the user to complete mediation testing with the user's own data in a single-step fashion. A technical manual included with the programming provides instruction on program use and interpretation of the output. Mediation modeling is a useful tool for describing the relation between three or more variables. Programming and manuals for using this model are made available.

  20. The Nature of Natural Hazards Communication (Invited)

    Science.gov (United States)

    Kontar, Y. Y.

    2013-12-01

    Some of the many issues of interest to natural hazards professionals include the analysis of proactive approaches to the governance of risk from natural hazards and approaches to broaden the scope of public policies related to the management of risks from natural hazards, as well as including emergency and environmental management, community development and spatial planning related to natural hazards. During the talk we will present results of scientific review, analysis and synthesis, which emphasize same new trends in communication of the natural hazards theories and practices within an up-to-the-minute context of new environmental and climate change issues, new technologies, and a new focus on resiliency. The presentation is divided into five sections that focus on natural hazards communication in terms of education, risk management, public discourse, engaging the public, theoretical perspectives, and new media. It includes results of case studies and best practices. It delves into natural hazards communication theories, including diffusion, argumentation, and constructivism, to name a few. The presentation will provide information about: (1) A manual of natural hazards communication for scientists, policymakers, and media; (2) An up-to-the-minute context of environmental hazards, new technologies & political landscape; (3) A work by natural hazards scientists for geoscientists working with social scientists and communication principles; (4) A work underpinned by key natural hazards communication theories and interspersed with pragmatic solutions; (5) A work that crosses traditional natural hazards boundaries: international, interdisciplinary, theoretical/applied. We will further explore how spatial planning can contribute to risk governance by influencing the occupation of natural hazard-prone areas, and review the central role of emergency management in risk policy. The goal of this presentation is to contribute to the augmentation of the conceptual framework

  1. Nanotoxicity of natural minerals: an emerging area of nanotoxicology.

    Science.gov (United States)

    Ahmad, Iqbal

    2011-02-01

    Nanotoxicity of two natural minerals, talc and silica were evaluated in vitro studying their effects on cell viability, LDH leakage, LPO induction, ROS production, GSH depletion, modulation of GR and GPx activities. Both mineral particles mediated their toxicity through oxidative stress. Differently, silica nanoparticles showed insignificant effect on GSH depletion. Talc nanoparticles significantly enhanced transcription and translation of TNF-alpha which was mediated by both ERK1/2 and P38. This aspect of study on silica nanoparticles is in progress.

  2. The impact of ruxolitinib treatment on inflammation-mediated comorbidities in myelofibrosis and related neoplasms

    DEFF Research Database (Denmark)

    Bjørn, Mads Emil; Hasselbalch, Hans Carl

    2015-01-01

    The inflammation-mediated comorbidities in myelofibrosis (MF) and related neoplasms (MPNs) likely reflect the concurrent immune deregulation and systemic inflammatory nature of the MPNs, emphasizing the link between chronic systemic inflammation, immune deregulation, and the malignant clone. JAK1......-2 inhibitors in MF-patients reduce constitutional symptoms and splenomegaly, but also taget autoimmune and inflammation-mediated comorbidities....

  3. Agrobacterium-mediated and electroporation-mediated transformation of Chlamydomonas reinhardtii: a comparative study.

    Science.gov (United States)

    Mini, Paola; Demurtas, Olivia Costantina; Valentini, Silvia; Pallara, Patrizia; Aprea, Giuseppe; Ferrante, Paola; Giuliano, Giovanni

    2018-02-17

    Chlamydomonas reinhardtii is an unicellular green alga used for functional genomics studies and heterologous protein expression. A major hindrance in these studies is the low level and instability of expression of nuclear transgenes, due to their rearrangement and/or silencing over time. We constructed dedicated vectors for Agrobacterium-mediated transformation carrying, within the T-DNA borders, the Paromomycin (Paro) selectable marker and an expression cassette containing the Luciferase (Luc) reporter gene. These vectors and newly developed co-cultivation methods were used to compare the efficiency, stability and insertion sites of Agrobacterium- versus electroporation-mediated transformation. The influence of different transformation methods, of the cell wall, of the virulence of different Agrobacterium strains, and of transgene orientation with respect to T-DNA borders were assessed. False positive transformants were more frequent in Agrobacterium-mediated transformation compared to electroporation, compensating for the slightly lower proportion of silenced transformants observed in Agrobacterium-mediated transformation than in electroporation. The proportion of silenced transformants remained stable after 20 cycles of subculture in selective medium. Next generation sequencing confirmed the nuclear insertion points, which occurred in exons or untraslated regions (UTRs) for 10 out of 10 Agrobacterium-mediated and 9 out of 13 of electroporation-mediated insertions. Electroporation also resulted in higher numbers of insertions at multiple loci. Due to its labor-intensive nature, Agrobacterium transformation of Chlamydomonas does not present significant advantages over electroporation, with the possible exception of its use in insertional mutagenesis, due to the higher proportion of within-gene, single-locus insertions. Our data indirectly support the hypothesis that rearrangement of transforming DNA occurs in the Chlamydomonas cell, rather than in the

  4. The practice of mediation to resolve clinical, bioethical, and medical malpractice disputes.

    Science.gov (United States)

    Lee, Danny W H; Lai, Paul B S

    2015-12-01

    Mediation is a voluntary process whereby a neutral and impartial third party-t-he mediator--is present to facilitate communication and negotiation between the disputing parties so that amicable settlements can be agreed. Being confidential and non-adversarial in nature, the mediation process and skills are particularly applicable in clinical practice to facilitate challenging communications following adverse events, to assist bioethical decision making and to resolve disputes. Mediation is also a more effective and efficient means of dispute resolution in medical malpractice claims when compared with civil litigation. Health care mediation teams should be set up at individual facilities to provide education and consultation services to frontline staff and patients. At a community level, the Government, the mediation community, and the health care professionals should join forces to promote mediation as a means to settle medical malpractice claims outside of the courtroom.

  5. Interpreter-mediated dentistry.

    Science.gov (United States)

    Bridges, Susan; Drew, Paul; Zayts, Olga; McGrath, Colman; Yiu, Cynthia K Y; Wong, H M; Au, T K F

    2015-05-01

    The global movements of healthcare professionals and patient populations have increased the complexities of medical interactions at the point of service. This study examines interpreter mediated talk in cross-cultural general dentistry in Hong Kong where assisting para-professionals, in this case bilingual or multilingual Dental Surgery Assistants (DSAs), perform the dual capabilities of clinical assistant and interpreter. An initial language use survey was conducted with Polyclinic DSAs (n = 41) using a logbook approach to provide self-report data on language use in clinics. Frequencies of mean scores using a 10-point visual analogue scale (VAS) indicated that the majority of DSAs spoke mainly Cantonese in clinics and interpreted for postgraduates and professors. Conversation Analysis (CA) examined recipient design across a corpus (n = 23) of video-recorded review consultations between non-Cantonese speaking expatriate dentists and their Cantonese L1 patients. Three patterns of mediated interpreting indicated were: dentist designated expansions; dentist initiated interpretations; and assistant initiated interpretations to both the dentist and patient. The third, rather than being perceived as negative, was found to be framed either in response to patient difficulties or within the specific task routines of general dentistry. The findings illustrate trends in dentistry towards personalized care and patient empowerment as a reaction to product delivery approaches to patient management. Implications are indicated for both treatment adherence and the education of dental professionals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Kyllinga brevifolia mediated greener silver nanoparticles

    Science.gov (United States)

    Isa, Norain; Bakhari, Nor Aziyah; Sarijo, Siti Halimah; Aziz, Azizan; Lockman, Zainovia

    2017-12-01

    Kyllinga brevifolia extract (KBE) was studied in this research as capping as well as reducing agent for the synthesis of greener plant mediated silver nanoparticles. This research was conducted in order to identify the compounds in the KBE that probable to work as reductant for the synthesis of Kyllinga brevifolia-mediated silver nanoparticles (AgNPs). Screening test such as Thin Layer Chromatography (TLC), Fourier Transform Infra-Red (FTIR), Carlo Erba Elemental analysis and Gas Chromatography-Mass Spectroscopy (GCMS) were used in identifying the natural compounds in KBE. The as-prepared AgNPs were characterized by UV-vis spectroscopy (UV-vis), Transmission Electron Microscope (TEM) and X-ray Diffraction (XRD). The TEM images showed that the as-synthesized silver have quasi-spherical particles are distributed uniformly with a narrow distribution from 5 nm to 40 nm. The XRD results demonstrated that the obtained AgNPs were face centre-cubic (FCC) structure. The catalytic activity of AgNPs on reduction of methylene blue (MB) using sodium borohydride (SB) was analyzed using UV-vis spectroscopy. This study showed that the efficacy of mediated AgNPs in catalysing the reduction of MB.

  7. Neural mechanisms mediating degrees of strategic uncertainty.

    Science.gov (United States)

    Nagel, Rosemarie; Brovelli, Andrea; Heinemann, Frank; Coricelli, Giorgio

    2018-01-01

    In social interactions, strategic uncertainty arises when the outcome of one's choice depends on the choices of others. An important question is whether strategic uncertainty can be resolved by assessing subjective probabilities to the counterparts' behavior, as if playing against nature, and thus transforming the strategic interaction into a risky (individual) situation. By means of functional magnetic resonance imaging with human participants we tested the hypothesis that choices under strategic uncertainty are supported by the neural circuits mediating choices under individual risk and deliberation in social settings (i.e. strategic thinking). Participants were confronted with risky lotteries and two types of coordination games requiring different degrees of strategic thinking of the kind 'I think that you think that I think etc.' We found that the brain network mediating risk during lotteries (anterior insula, dorsomedial prefrontal cortex and parietal cortex) is also engaged in the processing of strategic uncertainty in games. In social settings, activity in this network is modulated by the level of strategic thinking that is reflected in the activity of the dorsomedial and dorsolateral prefrontal cortex. These results suggest that strategic uncertainty is resolved by the interplay between the neural circuits mediating risk and higher order beliefs (i.e. beliefs about others' beliefs). © The Author(s) (2017). Published by Oxford University Press.

  8. The four-principle formulation of common morality is at the core of bioethics mediation method.

    Science.gov (United States)

    Ahmadi Nasab Emran, Shahram

    2015-08-01

    Bioethics mediation is increasingly used as a method in clinical ethics cases. My goal in this paper is to examine the implicit theoretical assumptions of the bioethics mediation method developed by Dubler and Liebman. According to them, the distinguishing feature of bioethics mediation is that the method is useful in most cases of clinical ethics in which conflict is the main issue, which implies that there is either no real ethical issue or if there were, they are not the key to finding a resolution. I question the tacit assumption of non-normativity of the mediation method in bioethics by examining the various senses in which bioethics mediation might be non-normative or neutral. The major normative assumption of the mediation method is the existence of common morality. In addition, the four-principle formulation of the theory articulated by Beauchamp and Childress implicitly provides the normative content for the method. Full acknowledgement of the theoretical and normative assumptions of bioethics mediation helps clinical ethicists better understand the nature of their job. In addition, the need for a robust philosophical background even in what appears to be a purely practical method of mediation cannot be overemphasized. Acknowledgement of the normative nature of bioethics mediation method necessitates a more critical attitude of the bioethics mediators towards the norms they usually take for granted uncritically as valid.

  9. Comments on General Gauge Mediation

    OpenAIRE

    Intriligator, Kenneth; Sudano, Matthew

    2008-01-01

    There has been interest in generalizing models of gauge mediation of supersymmetry breaking. As shown by Meade, Seiberg, and Shih (MSS), the soft masses of general gauge mediation can be expressed in terms of the current two-point functions of the susy-breaking sector. We here give a simple extension of their result which provides, for general gauge mediation, the full effective potential for squark pseudo-D-flat directions. The effective potential reduces to the sfermion soft masses near the...

  10. Mediating Trust in Terrorism Coverage

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    Mass mediated risk communication can contribute to perceptions of threats and fear of “others” and/or to perceptions of trust in fellow citizens and society to overcome problems. This paper outlines a cross-disciplinary holistic framework for research in mediated trust building during an acute...... crisis. While the framework is presented in the context of television coverage of a terror-related crisis situation, it can equally be used in connection with all other forms of mediated trust. Key words: National crisis, risk communication, crisis management, television coverage, mediated trust....

  11. Substrate mediated enzyme prodrug therapy

    DEFF Research Database (Denmark)

    Fejerskov, Betina; Jarlstad Olesen, Morten T; Zelikin, Alexander N

    2017-01-01

    Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug administra......Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug...

  12. Inflammatory mediators and intestinal injury.

    Science.gov (United States)

    Caplan, M S; MacKendrick, W

    1994-06-01

    Although the causes of necrotizing enterocolitis (NEC) are not well understood, there is compelling evidence to suggest that the inflammatory mediators play an important role in the pathophysiology of the disease. This article examines the role of platelet-activating factor (PAF) and other mediators on the development of NEC, and attempts to explain the association of the putative NEC risk factors with altered mediator production and subsequent intestinal injury. The authors hypothesize that PAF is a key mediator in the final common pathway leading to NEC.

  13. When Memories are Mediated

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    that are mediated through stories: told and retold as oral stories through generations, as myths or sagas, or remediated as contemporary documentary film accounts or more fictional film accounts. In these processes of retelling acts of violence, transformations of meanings across time, cultural, social...... and political contexts and media platforms take place and become contexts for audience reception. This paper explores two examples of narratives that construct memories of acts of mass violence: “Gzim Rewind” (Sweden, 2011, director Knutte Wester) about 1990’s Kosovo, and “The Act of Killing” (Denmark, 2012......, director Joshua Oppenheimer) about 1960’s Indonesia. The two films, in very different ways, focus on persons who tell about their involvement in acts of mass violence. Both films use live action footage in combination with fictional elements and settings, and both films also convey personal relationships...

  14. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    ’ [Shaviro, S., 2010. Post-cinematic affect. Winchester: Zero Books]. These intensity effects mediate between the age of terror's ecology of fear [Massumi, Brian, 2002. Parables for the virtual: movement, affect, sensation. Durham: Duke University Press] and our bodies. Rather than producing fear, action....... Adey, M. Whitehead, and A.J. Williams, eds. From above: war, violence and verticality. London: Hurst & Company]. Through a sensory assault of intense bass soundtracks, kinetic camera movements, and intense CGI effects action movies work to produce what Steven Shaviro has termed ‘intensity effects....... Robin James significantly posits a drone atmosphere where our perceptual limit reconfigures through ‘droning’ – the creation of an affective timbre [James, R., 2013. Drones, sound, and super-panoptic surveillance. Cyborgology]. As James argues, ‘[d]roning rivets you to material conditions, affects...

  15. Mediated Cultural Memories

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    (A revised, full paper will be published in the journal Mediekultur, spring 2014) This paper explores two examples of narratives representing memories of acts of mass violence: Gzim Rewind (Sweden, 2011, director Knutte Wester) about 1990’s Kosovo, and The Act of Killing (Denmark, 2012, director...... perspectives of semiosis (meaning-making) in relation to the films as redefining genres and what sorts of meanings different audiences create about the films. Acts of mass violence, including murder on civilians, genocide, and wars, can be seen as seeds for memories of the involved persons and following...... generations. Acts of mass violence also construct a sort of looking glass of culturally dominant memories that are mediated through stories: retold as oral stories through generations, as myths or sagas, or remediated in contemporary documentary or fiction films. In these processes of retelling acts...

  16. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    Social actors see exposure in the news media as attractive for publicity purposes and are under pressure to adapt their press work to a “media logic” to be attractive sources for journalists and editors. This article investigates the European Parliament’s press officers’ professional practices...... in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs......” in their communication efforts, and that they face a daily professional challenge as they attempt to promote the European Parliament and its activities to the news media in a way that will not compromise their credibility as government sources. The study provides new insights into communicative aspects of EU governance...

  17. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    relations between individuals and social contexts, aesthetics and production, distribution and consumption, as well as relations between fluidity and stability. By addressing the field of fashion, the paper proposes to shed light on an empirical setting which has so far been studied either as a purely......This paper discusses relations between aesthetics of fashion and the sociality of fashion. It takes as its premise that aesthetics and sociality are co-constructed, and cannot be regarded as separate - although this has been the norm in the academic traditions of aesthetics and sociology...... to STS literature by expanding one of its central debates to a new empirical setting; fashion specifically, and the aesthetic-cultural field on a more general level. In trying to make a theoretical connection between aesthetics and sociality of fashion, the paper suggests the term of "mediator" (Hennion...

  18. Endosome-mediated autophagy

    Science.gov (United States)

    Kondylis, Vangelis; van Nispen tot Pannerden, Hezder E.; van Dijk, Suzanne; ten Broeke, Toine; Wubbolts, Richard; Geerts, Willie J.; Seinen, Cor; Mutis, Tuna; Heijnen, Harry F.G.

    2013-01-01

    Activation of TLR signaling has been shown to induce autophagy in antigen-presenting cells (APCs). Using high-resolution microscopy approaches, we show that in LPS-stimulated dendritic cells (DCs), autophagosomes emerge from MHC class II compartments (MIICs) and harbor both the molecular machinery for antigen processing and the autophagosome markers LC3 and ATG16L1. This ENdosome-Mediated Autophagy (ENMA) appears to be the major type of autophagy in DCs, as similar structures were observed upon established autophagy-inducing conditions (nutrient deprivation, rapamycin) and under basal conditions in the presence of bafilomycin A1. Autophagosome formation was not significantly affected in DCs expressing ATG4BC74A mutant and atg4b−/− bone marrow DCs, but the degradation of the autophagy substrate SQSTM1/p62 was largely impaired. Furthermore, we demonstrate that the previously described DC aggresome-like LPS-induced structures (DALIS) contain vesicular membranes, and in addition to SQSTM1 and ubiquitin, they are positive for LC3. LC3 localization on DALIS is independent of its lipidation. MIIC-driven autophagosomes preferentially engulf the LPS-induced SQSTM1-positive DALIS, which become later degraded in autolysosomes. DALIS-associated membranes also contain ATG16L1, ATG9 and the Q-SNARE VTI1B, suggesting that they may represent (at least in part) a membrane reservoir for autophagosome expansion. We propose that ENMA constitutes an unconventional, APC-specific type of autophagy, which mediates the processing and presentation of cytosolic antigens by MHC class II machinery, and/or the selective clearance of toxic by-products of elevated ROS/RNS production in activated DCs, thereby promoting their survival. PMID:23481895

  19. Natural short sleeper

    Science.gov (United States)

    Sleep - natural short sleeper ... 7 to 9 hours of sleep each night. Short sleepers sleep less than 75% of what is normal for their age. Natural short sleepers are different from people who chronically do ...

  20. Natural gas annual 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    This document provides information on the supply and disposition of natural gas to a wide audience. The 1996 data are presented in a sequence that follows natural gas from it`s production to it`s end use.

  1. Vermont Natural Resources Atlas

    Data.gov (United States)

    Vermont Center for Geographic Information — The purpose of the�Natural Resources Atlas�is to provide geographic information about environmental features and sites that the Vermont Agency of Natural Resources...

  2. Natural Weathering Exposure Station

    Data.gov (United States)

    Federal Laboratory Consortium — The Corps of Engineers' Treat Island Natural Weathering Exposure Station is a long-term natural weathering facility used to study concrete durability. Located on the...

  3. Natural Language Processing

    OpenAIRE

    Preeti; BrahmaleenKaurSidhu

    2013-01-01

    Natural language processing (NLP) work began more than sixty years ago; it is a field of computer science and linguistics devoted to creating computer systems that use human (natural) language. Natural Language Processing holds great promise for making computer interfaces that are easier to use for people, since people will be able to talk to the computer in their own language, rather than learn a specialized language of computer commands. Natural Language processing techniques can make possi...

  4. Natural gas annual 1993

    International Nuclear Information System (INIS)

    1994-01-01

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1993 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. Tables summarizing natural gas supply and disposition from 1989 to 1993 are given for each Census Division and each State. Annual historical data are shown at the national level

  5. Natural gas annual 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-17

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1994 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1990 to 1994 for each Census Division and each State. Annual historical data are shown at the national level.

  6. Natural gas annual 1995

    International Nuclear Information System (INIS)

    1996-11-01

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1995 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1991 to 1995 for each Census Division and each State. Annual historical data are shown at the national level

  7. Natural gas annual 1991

    International Nuclear Information System (INIS)

    1992-01-01

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1991 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. Tables summarizing natural gas supply and disposition form 1987 to 1991 are given for each Census Division and each State. Annual historical data are shown at the national level

  8. Natural Gas Basics

    Energy Technology Data Exchange (ETDEWEB)

    2016-06-01

    Natural gas powers about 150,000 vehicles in the United States and roughly 22 million vehicles worldwide. Natural gas vehicles (NGVs) are a good choice for high-mileage fleets -- such as buses, taxis, and refuse vehicles -- that are centrally fueled or operate within a limited area or along a route with natural gas fueling stations. This brochure highlights the advantages of natural gas as an alternative fuel, including its domestic availability, established distribution network, relatively low cost, and emissions benefits.

  9. Natural Gas Basics

    Energy Technology Data Exchange (ETDEWEB)

    None

    2016-06-08

    Natural gas powers about 150,000 vehicles in the United States and roughly 22 million vehicles worldwide. Natural gas vehicles (NGVs) are a good choice for high-mileage fleets -- such as buses, taxis, and refuse vehicles -- that are centrally fueled or operate within a limited area or along a route with natural gas fueling stations. This brochure highlights the advantages of natural gas as an alternative fuel, including its domestic availability, established distribution network, relatively low cost, and emissions benefits.

  10. The mediation procedure in Romania

    Directory of Open Access Journals (Sweden)

    Alexandrina Zaharia

    2009-06-01

    Full Text Available The mediation activity as an alternative way of solving conflicts occupies an important place in modernsociety. Currently, the mediation reached its maturity worldwide being adopted without reservations.The future of solving conflicts is undoubtedly closely related to mediation. XXth century is the century of solvingconflicts amiably outside the court room. In Romania and the mediation profession were regulated by the Law no.192/2006, on the basis of the idea that mediation is one of the major themes of the reform strategy of the judicialsystem 2005-2007. By adopting the mentioned law it was followed the idea of reducing the volume of activitycourts, and therefore, relieve them of as many cases, with the direct effect on the quality of justice. Mediation is avoluntary process in which the parties with a neutral and impartial third party, without power of decision - themediator - who is qualified to assist the parties to negotiate, facilitating the communication between them andhelping them to reach a unanimous effective and sustainable agreement. The parties may resort to mediation beforeor after triggering a trial. Mediation can be applied, in principle, on any type of conflict. However, theRomanian legislator has established special stipulations on conflict mediation in criminal, civil and familylaw. Although not expressly provided, the stipulations regarding the civil conflicts and also apply to commercialconflicts. Therefore, the mediation is applicable to most types of lawsuits, except those relating to personalrights. As a "win- win" principle, the mediation does not convert any of the parties defeated or victorious; allthose involved have gained by applying this procedure.

  11. Natural gas annual 1991

    International Nuclear Information System (INIS)

    1993-01-01

    The Natural Gas Annual 1991 provides information on the supply and disposition of natural gas to a wide audience including industry, consumers Federal and State agencies, and education institutions. This report, the Natural Gas Annual 1991 Supplement: Company Profiles, presents a detailed profile of selected companies

  12. Naturalisms and religion

    NARCIS (Netherlands)

    Drees, Willem

    1997-01-01

    Such terms as materialism, naturalism, and near synonyms evoke strong negative reactions among many believers. However, the notion of naturalism has various meanings; implications for religion differ for the several varieties of naturalism. In this paper I analyze epistemological and ontological

  13. Natural gas for vehicles

    International Nuclear Information System (INIS)

    Prieur, A.

    2006-01-01

    Following a decade-long upsurge in the use of natural gas in the energy sector (heating and especially electricity), new outlets for natural gas are being developed in the transport sector. For countries endowed with substantial local resources, development in this sector can help reduce oil dependence. In addition, natural gas is often used to reduce pollution, particularly in cities

  14. Nature and Health

    NARCIS (Netherlands)

    Hartig, T.; Mitchell, R.; Vries, de S.; Frumkin, H.

    2014-01-01

    Urbanization, resource exploitation, and lifestyle changes have diminished possibilities for human contact with nature in urbanized societies. Concern about the loss has helped motivate research on the health benefits of contact with nature. Reviewing that research here, we focus on nature as

  15. Identifying Sources of Clinical Conflict: A Tool for Practice and Training in Bioethics Mediation.

    Science.gov (United States)

    Bergman, Edward J

    2015-01-01

    Bioethics mediators manage a wide range of clinical conflict emanating from diverse sources. Parties to clinical conflict are often not fully aware of, nor willing to express, the true nature and scope of their conflict. As such, a significant task of the bioethics mediator is to help define that conflict. The ability to assess and apply the tools necessary for an effective mediation process can be facilitated by each mediator's creation of a personal compendium of sources that generate clinical conflict, to provide an orientation for the successful management of complex dilemmatic cases. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

  16. Capturing Nature's Diversity

    Science.gov (United States)

    Pascolutti, Mauro; Campitelli, Marc; Nguyen, Bao; Pham, Ngoc; Gorse, Alain-Dominique; Quinn, Ronald J.

    2015-01-01

    Natural products are universally recognized to contribute valuable chemical diversity to the design of molecular screening libraries. The analysis undertaken in this work, provides a foundation for the generation of fragment screening libraries that capture the diverse range of molecular recognition building blocks embedded within natural products. Physicochemical properties were used to select fragment-sized natural products from a database of known natural products (Dictionary of Natural Products). PCA analysis was used to illustrate the positioning of the fragment subset within the property space of the non-fragment sized natural products in the dataset. Structural diversity was analysed by three distinct methods: atom function analysis, using pharmacophore fingerprints, atom type analysis, using radial fingerprints, and scaffold analysis. Small pharmacophore triplets, representing the range of chemical features present in natural products that are capable of engaging in molecular interactions with small, contiguous areas of protein binding surfaces, were analysed. We demonstrate that fragment-sized natural products capture more than half of the small pharmacophore triplet diversity observed in non fragment-sized natural product datasets. Atom type analysis using radial fingerprints was represented by a self-organizing map. We examined the structural diversity of non-flat fragment-sized natural product scaffolds, rich in sp3 configured centres. From these results we demonstrate that 2-ring fragment-sized natural products effectively balance the opposing characteristics of minimal complexity and broad structural diversity when compared to the larger, more complex fragment-like natural products. These naturally-derived fragments could be used as the starting point for the generation of a highly diverse library with the scope for further medicinal chemistry elaboration due to their minimal structural complexity. This study highlights the possibility to capture a

  17. Theorizing with/out "Mediators".

    Science.gov (United States)

    Roth, Wolff-Michael; Jornet, Alfredo

    2017-01-05

    Mediation is one of the most often cited concepts in current cultural-historical theory literature, in which cultural actions and artifacts are often characterized as mediators standing between situational stimuli and behavioral responses. Most often presented as a means to overcome Cartesian dualism between subject and object, and between individual and society, some scholars have nonetheless raised criticism suggesting that such mediators are problematic for a dialectical psychology that takes a unit analysis (monist) approach. In fact, Spinoza develops a monist theory of mind and body that goes without and even excludes every form of mediation. In this study, we follow up on the latter criticisms and explore what we consider to be problematic uses of the notion of mediation as an analytical construct in the literature. We elaborate an empirically grounded discussion on the ways the concept of mediation may lead to dualistic readings; and we offer an alternative account where the notion of mediator is not needed. We conclude discussing prospects for and implications of a cultural-historical theory where the notion of mediation no longer is invoked to account for human action and development.

  18. Nature in Preschool

    DEFF Research Database (Denmark)

    Husted, Mia; Frøkjær, Thorleif

    Nature and nature phenomena’ has formed a specific curriculum theme in Danish preschool since early childhood curriculum was prescribed by law in 2004. However, recent evaluations show that the implementation of an early childhood curriculum has not produced an increased pedagogical focus...... on ‘nature and nature phenomena’ in preschools (EVA 2012). This finding, along with an increased political interest in goals and measurable outcome of early childhood curriculum (Broström 2012), will be the starting point in our ambition to carry out a more thorough qualitative investigation into links...... between preschool teachers’ understanding and interest in teaching nature and the rather poor evaluation....

  19. Natural gas marketing II

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    This book covers all aspects of gas marketing, from the basic regulatory structure to the latest developments in negotiating agreements and locating markets. Topics include: Federal regulation of the gas industry; Fundamentals of gas marketing contracts; FERC actions encouraging competitive markets; Marketing conditions from the pipelines' perspective; State non-utility regulation of natural gas production, transportation, and marketing; Natural gas wellhead agreements and tariffs; Natural gas processing agreements; Effective management of producer's natural gas contracts; Producer-pipeline litigation; Natural gas purchasing from the perspective of industrial gas users; Gas marketing by co-owners: problems of disproportionate sales, gas balancing, and accounting to royalty owners; Alternatives and new directions in marketing

  20. Practical Guide to Civil Mediation

    CERN Multimedia

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of International Organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreem...

  1. Practical Guide to Civil Mediation

    CERN Multimedia

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of international organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreeme...

  2. Comments on general gauge mediation

    International Nuclear Information System (INIS)

    Intriligator, Kenneth; Sudano, Matthew

    2008-01-01

    There has been interest in generalizing models of gauge mediation of supersymmetry breaking. As shown by Meade, Seiberg, and Shih (MSS), the soft masses of general gauge mediation can be expressed in terms of the current two-point functions of the susy-breaking sector. We here give a simple extension of their result which provides, for general gauge mediation, the full effective potential for squark pseudo-D-flat directions. The effective potential reduces to the sfermion soft masses near the origin, and the full potential, away from the origin, can be useful for cosmological applications. We also generalize the soft masses and effective potential to allow for general gauge mediation by Higgsed gauge groups. Finally, we discuss general gauge mediation in the limit of small F-terms, and how the results of MSS connect with the analytic continuation in superspace results, based on a spurion analysis.

  3. Psoriasis: epidemiology, natural history, and differential diagnosis

    Directory of Open Access Journals (Sweden)

    Basko-Plluska JL

    2012-09-01

    Full Text Available Juliana L Basko-Plluska, Vesna Petronic-RosicDepartment of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USAAbstract: Psoriasis is a chronic, immune-mediated, inflammatory disease which affects primarily the skin and joints. It occurs worldwide, but its prevalence varies considerably between different regions of the world. Genetic susceptibility as well as environmental factors play an important role in determining the development and prognosis of psoriasis. Genome-wide association studies have identified many genetic loci as potential psoriasis susceptibility regions, including PSORS1 through PSORS7. Histocompatibility antigen (HLA studies have also identified several HLA antigens, with HLA-Cw6 being the most frequently associated antigen. Epidemiological studies identified several modifiable risk factors that may predispose individuals to developing psoriasis or exacerbate pre-existing disease. These include smoking, obesity, alcohol consumption, diet, infections, medications and stressful life events. The exact mechanism by which they trigger psoriasis remains to be elucidated; however, existing data suggest that they are linked through Th1-mediated immunological pathways. The natural history of psoriasis varies depending on the clinical subtype as well as special circumstances, including pregnancy and HIV infection. In general, psoriasis is a chronic disease with intermittent remissions and exacerbations. The differential diagnosis is vast and includes many other immune-mediated, inflammatory disorders.Keywords: psoriasis, epidemiology, natural history, differential diagnosis

  4. Mediated Communities in the Age of Electronic Communication

    Directory of Open Access Journals (Sweden)

    Gábor Szécsi

    2012-01-01

    Full Text Available The electronically mediated communication has transformed our notionof the relation between place and community. With a greater proportionof our communicative acts taking place via electronic media, physical co-presence, the co-located interpersonal relations are diminishing as determinants of the nature of human interactions. This paper argues that the electronically mediated communication contributes to the construction of new, mediated forms of communities which are based on the interaction or operational synthesis of virtual and physical communities. The appearance of these new forms of communitiesleads to a new conceptualization of the relation between self and community. The aim of this paper is to show that the medium of the mediatization and new conceptualization of community is a specific pictorial language of electronically mediated communication, the semantic structure of which offers new opportunities to grasp and understand the complex notion of new mediated communities and to adopt the idea of a new global, community building language in local and national communities.

  5. IgE-mediated reaction to local anaesthetics

    International Nuclear Information System (INIS)

    Kartal, O.; Gulec, M.; Sener, O.; Caliskaner, A.Z.

    2013-01-01

    Local anaesthetics (LAs) are essential agents in daily practices of dentistry, minor surgery and dermatology. Although they have an impressive history of safety and efficacy, LAs also have the potential to produce adverse events, which are mainly of non-immune nature. The true IgE-mediated allergies are quite rare, but are more considerable in terms of ability to cause life-threatening outcomes. In this report, we present a case of IgE-mediated systemic reaction to LAs occurring during epidural anaesthesia for Cesarean section. (author)

  6. On nature and bioethics.

    Science.gov (United States)

    Peterson, Paul Silas

    2010-01-01

    The account of nature and humanity's relationship to nature are of central importance for bioethics. The Scientific Revolution was a critical development in the history of this question and many contemporary accounts of nature find their beginnings here. While the innovative approach to nature going out of the seventeenth century was reliant upon accounts of nature from the early modern period, the Middle Ages, late-antiquity and antiquity, it also parted ways with some of the understandings of nature from these epochs. Here I analyze this development and suggests that some of the insights from older understandings of nature may be helpful for bioethics today, even if there can be no simple return to them.

  7. 34 CFR 81.13 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 81.13 Section 81.13 Education Office of the... Mediation. (a) Voluntary mediation is available for proceedings that are pending before the OALJ. (b) A... mediation by filing a motion with the ALJ assigned to the case. The OALJ arranges for a mediator if the...

  8. 24 CFR 3288.35 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Mediation. 3288.35 Section 3288.35...-Administered States § 3288.35 Mediation. (a) Mediator. The dispute resolution provider will provide for the... identifies any other party that should be included in the mediation, the mediator will contact the other...

  9. 44 CFR 7.942 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Mediation. 7.942 Section 7..., Conciliation, and Enforcement Procedures § 7.942 Mediation. (a) FEMA will promptly refer to a mediation agency... participate in the mediation process to the extent necessary to reach an agreement or for the mediator to make...

  10. 29 CFR 1202.1 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation. 1202.1 Section 1202.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.1 Mediation. The mediation..., or where conferences are refused. The National Mediation Board may proffer its services in case any...

  11. 29 CFR 35.32 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Mediation. 35.32 Section 35.32 Labor Office of the Secretary... Mediation. (a) Referral to mediation. CRC will promptly refer to the Federal Mediation and Conciliation Service or the mediation agency designated by the Secretary of Health and Human Services under 45 CFR part...

  12. 29 CFR 1203.1 - Mediation services.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation services. 1203.1 Section 1203.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD APPLICATIONS FOR SERVICE § 1203.1 Mediation services. Applications for the mediation services of the National Mediation Board under section 5, First, of the Railway...

  13. 22 CFR 143.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 143.33 Section 143.33 Foreign... Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and... participate in the mediation process to the extent necessary to reach an agreement or make an informed...

  14. 32 CFR 776.38 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Mediation. 776.38 Section 776.38 National... Professional Conduct § 776.38 Mediation. (a) Mediation: (1) A covered attorney may act as a mediator between... mediation, including the advantages and risks involved, and the effect on the attorney-client...

  15. Chaperone-Mediated Autophagy

    Science.gov (United States)

    Bejarano, Eloy; Cuervo, Ana Maria

    2010-01-01

    Continuous renewal of intracellular components is required to preserve cellular functionality. In fact, failure to timely turnover proteins and organelles leads often to cell death and disease. Different pathways contribute to the degradation of intracellular components in lysosomes or autophagy. In this review, we focus on chaperone-mediated autophagy (CMA), a selective form of autophagy that modulates the turnover of a specific pool of soluble cytosolic proteins. Selectivity in CMA is conferred by the presence of a targeting motif in the cytosolic substrates that, upon recognition by a cytosolic chaperone, determines delivery to the lysosomal surface. Substrate proteins undergo unfolding and translocation across the lysosomal membrane before reaching the lumen, where they are rapidly degraded. Better molecular characterization of the different components of this pathway in recent years, along with the development of transgenic models with modified CMA activity and the identification of CMA dysfunction in different severe human pathologies and in aging, are all behind the recent regained interest in this catabolic pathway. PMID:20160146

  16. Caspases: An apoptosis mediator

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Palai

    2015-03-01

    Full Text Available The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy - dependent biochemical mechanisms. Apoptosis is a widely conserved phenomenon helping many processes, including normal cell turnover, proper development and functioning of the immune system, hormone dependent atrophy etc. Inappropriate apoptosis (either low level or high level leads to many developmental abnormalities like, neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. To use cells for therapeutic purposes through generating cell lines, it is critical to study the cell cycle machinery and signalling pathways that controls cell death and apoptosis. Apoptotic pathways provide a fundamental protective mechanism that decreases cellular sensitivity to damaging events and allow proper developmental process in multi-cellular organisms. Major mediator of apoptosis is a family of proteins known as caspases. There are mainly fourteen types of caspases but out of them only ten caspasese have got essential role in controlling the process of apoptosis. These ten caspases have been categorized into either initiator caspases (caspase 2, 8, 9, 10 or executioner caspases (caspase 3, 6, 7. Although various types of caspases have been identified so far, the exact mechanisms of action of these groups of proteins is still to be fully understood. The aim of this review is to provide a detail overview of role of different caspases in regulating the process of apoptosis.

  17. What's nature got to do with it? A situated historical perspective on socio-natural commodities.

    Science.gov (United States)

    Peluso, Nancy Lee

    2012-01-01

    Nature(s) have been commodified since the early days of capitalism, but through processes and socio-natural relationships mediated by their times, histories and localities. While the conditions under which nature's commodities are being trademarked today may be new, their potential for commodification is not. Commodifications of nature should not come as a surprise to environmental social scientists and activists. In this article, I argue that commodification of ‘nature's products, places and processes’ produces new sorts of socio-natures. Situated histories of rubber are particularly relevant because, like carbon, ecosystem services and other recently commodified natures, rubber sits comfortably on the line between a fictitious commodity and a commodity produced explicitly for market: the latex alone has almost no use value, and to give it any exchange value, it requires processing. Yet analytically, it is still considered a ‘natural commodity’, different from ‘synthetic rubber’ and other tradable tree latexes in qualities and socio-natural characteristics. However, it is the social relations constituting rubber's production and trade in various rainforest and agro-forestry environments that have given it a positive or negative connotation, rather than its natural properties or the ecological contexts within which it has been produced. By situating rubber in three of its globally important temporal and spatial contexts, I show how it has been subjected to fairy-tale-like stories that masked and naturalized its commodity lives of the moment. Understanding how history is told or remains untold is thus an essential part of the politics of knowledge production, but also of human experience and mobilization for change. It should be part of any political ecology analysis.

  18. Nature as Dissonant Heritage

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel

    2014-01-01

    Many former sites of land reclamation, where rivers and wetlands have been cultivated for the purpose of modern agriculture, are now subject to projects of nature restoration. In this context nature is often referred to as ‘the nature’ or simply ‘nature’ as it was something objective and self......-evident. But who define and decide what kind of nature to restore? And is nature restoration not a contradiction in terms in our deeply cultivated landscapes? To examine these questions it makes sense to draw parallels between nature restoration and the concept of ‘dissonant heritage’ (Ashworth 2010), which...... concerns situations of mismatch between people and their heritage. The aim of the paper is to uncover the latent cultural dissonance in relation to nature restoration and to explain how landscape architecture could play an important role in the management of this dissonance. If one accepts that heritage...

  19. Nature and health.

    Science.gov (United States)

    Hartig, Terry; Mitchell, Richard; de Vries, Sjerp; Frumkin, Howard

    2014-01-01

    Urbanization, resource exploitation, and lifestyle changes have diminished possibilities for human contact with nature in urbanized societies. Concern about the loss has helped motivate research on the health benefits of contact with nature. Reviewing that research here, we focus on nature as represented by aspects of the physical environment relevant to planning, design, and policy measures that serve broad segments of urbanized societies. We discuss difficulties in defining "nature" and reasons for the current expansion of the research field, and we assess available reviews. We then consider research on pathways between nature and health involving air quality, physical activity, social cohesion, and stress reduction. Finally, we discuss methodological issues and priorities for future research. The extant research does describe an array of benefits of contact with nature, and evidence regarding some benefits is strong; however, some findings indicate caution is needed in applying beliefs about those benefits, and substantial gaps in knowledge remain.

  20. Mediation of information and educational mediation: conceptual discussions

    Directory of Open Access Journals (Sweden)

    Helena Célia de Souza Sacerdote

    2016-04-01

    Full Text Available Introduction: This is systematization of theoretical and methodological contributions related to the concepts of mediation information and pedagogical mediation in the literature. Objective: To understand possible intersection of information science and Online Education with regard to these concepts to check that both can be considered as analogous in its essence and practice. Methodology: Literature review based on literature by consulting the scientific productions selected in search of SciELO.ORG databases and EBSCO Host, the portal of CAPES / MEC and Google Scholar. Results: The most cited concepts in information science and education were de Almeida Junior (2009 and Masetto (2013, respectively. Conclusion: It is observed that the concept of mediation can move interchangeably between both areas. This is because the evidence found in the productions of the last five years indicate that the concept of information of mediation seems to have found its bases in education (educational psychology.

  1. Doing statistical mediation and moderation

    CERN Document Server

    Jose, Paul E

    2013-01-01

    Written in a friendly, conversational style, this book offers a hands-on approach to statistical mediation and moderation for both beginning researchers and those familiar with modeling. Starting with a gentle review of regression-based analysis, Paul Jose covers basic mediation and moderation techniques before moving on to advanced topics in multilevel modeling, structural equation modeling, and hybrid combinations, such as moderated mediation. User-friendly features include numerous graphs and carefully worked-through examples; ""Helpful Suggestions"" about procedures and pitfalls; ""Knowled

  2. Assay of mast cell mediators

    DEFF Research Database (Denmark)

    Rådinger, Madeleine; Jensen, Bettina M; Swindle, Emily

    2015-01-01

    Mediator release from activated mast cells is a major initiator of the symptomology associated with allergic disorders such as anaphylaxis and asthma. Thus, methods to monitor the generation and release of such mediators have widespread applicability in studies designed to understand the processes...... regulating mast cell activation and for the identification of therapeutic approaches to block mast cell-driven disease. In this chapter, we discuss approaches used for the determination of mast cell degranulation, lipid-derived inflammatory mediator production, and cytokine/chemokine gene expression as well...

  3. The mediatization of ethical consumption

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2013-01-01

    Over the years, mediatization studies have investigated the influence of media in numerous sections of contemporary society. One area that has received limited attention is the mediatization of consumption, particularly issues concerning ethical consumption. This article presents a study of how...... mediatization is transforming modern consumption and contributing to the mainstreaming of ethical consumption. Based on a study of a Danish online eco-store, the article argues that modern ethical consumption increasingly depends on new media practices to present sustainable consumption as practical...

  4. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Science.gov (United States)

    Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

  5. Natural gas annual 1997

    International Nuclear Information System (INIS)

    1998-10-01

    The Natural Gas Annual provides information on the supply and disposition of natural gas to a wide audience including industry, consumers, Federal and State agencies, and educational institutions. The 1997 data are presented in a sequence that follows natural gas (including supplemental supplies) from its production to its end use. This is followed by tables summarizing natural gas supply and disposition from 1993 to 1997 for each Census Division and each State. Annual historical data are shown at the national level. 27 figs., 109 tabs

  6. The City and Nature

    Directory of Open Access Journals (Sweden)

    Eduard Tovmasyan

    2016-09-01

    Full Text Available Animate “nature–1” around us is transforming into supported or non-supported by man “nature-2” within the framework of the urban development of town areas. Interaction of town and nature is a bilateral process. Experts underline 4 groups of town planning risks related to the interaction of town and nature: ecological, natural and biosphere, sanitary-epidemiologic risks as well as planning and management risks. The latter is often connected with protest population activities. The magazine is looking forward to readers comments.

  7. Natural gas outlook

    International Nuclear Information System (INIS)

    Molyneaux, M.P.

    1998-01-01

    An overview of natural gas markets in Canada and in the United States was provided. The major factors that determine the direction of natural gas prices were depicted graphically. Price volatility has decreased in recent months. As expected, April through November total energy consumption reached historically high levels. Demand for natural gas during the summer of 1997 was not as strong as anticipated. Nuclear energy appears to be on the slippery slope, with natural gas-driven electricity projects to fill the void. Hydroelectricity had a strong showing in 1997. Prospects are less bright for 1998 due to above average temperatures. Canadian natural gas export capacity has increased 5.5 times between 1986 and estimated 1999 levels. Despite this, in 1997, deliveries to the United States were marginally behind expectations. Natural gas consumption, comparative fuel prices, natural gas drilling activity, natural gas storage capacity, actual storage by region, and average weekly spot natural gas prices, for both the U. S. and Canada, were also provided. With regard to Canada, it was suggested that Canadian producers are well positioned for a significant increase in their price realization mostly because of the increase in Canada's export capacity in 1997 (+175 Mmcf/d), 1998 (1,060 Mmcf/d) and potentially in 1999 or 2000, via the Alliance Pipeline project. Nevertheless, with current production projections it appears next to impossible to fill the 10.9 Bcf/d of export capacity that will be potentially in place by the end of 1999. tabs., figs

  8. Nature-based integration

    DEFF Research Database (Denmark)

    Pitkänen, Kati; Oratuomi, Joose; Hellgren, Daniela

    Increased attention to, and careful planning of the integration of migrants into Nordic societies is ever more important. Nature based integration is a new solution to respond to this need. This report presents the results of a Nordic survey and workshop and illustrates current practices of nature...... based integration by case study descriptions from Denmark, Sweden Norway and Finland. Across Nordic countries several practical projects and initiatives have been launched to promote the benefits of nature in integration and there is also growing academic interest in the topic. Nordic countries have...... the potential of becoming real forerunners in nature based integration even at the global scale....

  9. Cytomegalovirus evasion of natural killer cell responses.

    Science.gov (United States)

    Farrell, H E; Degli-Esposti, M A; Davis-Poynter, N J

    1999-04-01

    Natural killer (NK) cells are an important component of the innate cellular immune system. They are particularly important during the early immune responses following virus infection, prior to the induction of cytotoxic T cells (CTL). Unlike CTL, which recognize specific peptides displayed on the surface of cells by class I MHC, NK cells respond to aberrant expression of cell surface molecules, in particular class I MHC, in a non-specific manner. Thus, cells expressing low levels of surface class I MHC are susceptible to recognition by NK cells, with concomitant triggering of cytolytic and cytokine-mediated responses. Many viruses, including the cytomegaloviruses, downregulate cell surface MHC class I: this is likely to provide protection against CTL-mediated clearance of infected cells, but may also render infected cells sensitive to NK-cell attack. This review focuses upon cytomegalovirus-encoded proteins that are believed to promote evasion of NK-cell-mediated immunity. The class I MHC homologues, encoded by all cytomegaloviruses characterised to date, have been implicated as molecular 'decoys', which may mimic the ability of cellular MHC class I to inhibit NK-cell functions. Results from studies in vitro are not uniform, but in general they support the proposal that the class I homologues engage inhibitory receptors from NK cells and other cell types that normally interact with cellular class I. Consistent with this, in vivo studies of murine cytomegalovirus indicate that the class I homologue is required for efficient evasion of NK-cell-mediated clearance. Recently a second murine cytomegalovirus protein, a C-C chemokine homologue, has been implicated as promoting evasion of NK and T-cell-mediated clearance in vivo.

  10. Natural killer T cells in adipose tissue prevent insulin resistance

    NARCIS (Netherlands)

    Schipper, H.S.; Rakhshandehroo, M.; Graaf, van de S.F.J.; Venken, K.; Koppen, A.; Stienstra, R.; Prop, S.; Meerding, J.; Hamers, N.; Besra, G.S.; Boon, den L.; Nieuwenhuis, E.E.S.; Elewaut, D.; Prakken, B.; Kersten, A.H.; Boes, M.; Kalkhoven, E.

    2012-01-01

    Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased

  11. [Mediation model in adolescent psychology].

    Science.gov (United States)

    Deguitre, Marie; Pascal-Verdelhan, Chantal; Saez, Catherine; Calmels, Marie-Jeanne; Nesensohn, Jessica; Legras, Stéphanie; Paradis, Martine

    2014-01-01

    Body mediation is today used as a tool for establishing a relationship with a young person experiencing psychological suffering. It is particularly useful in adolescence, a period marked by the destabilisation of emotional and relational fields.

  12. Inflammatory mediators of neuropathic pain

    OpenAIRE

    Oliveira Júnior, José Oswaldo de; Portella Junior, Caio Sander Andrade; Cohen, Cláudia Panossian

    2016-01-01

    ABSTRACT BACKGROUND AND OBJECTIVES: Pro-inflammatory chemical mediators and algogenic substances seem to be confused by the sharing of their actions and by interactions in painful and inflammatory presentation. This study aimed at presenting a review of major inflammatory chemical mediators and place them in neuropathic pain pathophysiology. CONTENTS: Inflammation is the homeostatic response of vascularized tissues to remove harmful agents and restore their normal functions. Nervous system ...

  13. Dimensional reduction in anomaly mediation

    Science.gov (United States)

    Boyda, Ed; Murayama, Hitoshi; Pierce, Aaron

    2002-04-01

    We offer a guide to dimensional reduction in theories with anomaly-mediated supersymmetry breaking. Evanescent operators proportional to ɛ arise in the bare Lagrangian when it is reduced from d=4 to d=4-2ɛ dimensions. In the course of a detailed diagrammatic calculation, we show that inclusion of these operators is crucial. The evanescent operators conspire to drive the supersymmetry-breaking parameters along anomaly-mediation trajectories across heavy particle thresholds, guaranteeing the ultraviolet insensitivity.

  14. Early modern natural history

    Indian Academy of Sciences (India)

    Early modern natural history: Contributions from the Americas and India. Rajesh Kochhar. Perspectives Volume 37 Issue ... Keywords. India; medical botany; natural history; scientific botany; the Americas. Author Affiliations. Rajesh Kochhar1. Indian Institute of Science Education and Research, Mohali 140 306 Punjab, India ...

  15. Nature Foil Reliefs

    Science.gov (United States)

    Lane, Shaw J.

    2012-01-01

    Nature has always been a source of inspiration for artists across the centuries. Artists such as Leonardo da Vinci, Georgia O'Keeffe, Ansel Adams, and Andy Goldsworthy all drew inspiration for their work from nature. Seeds come from the dried pods, which when planted and cared for, bear fruit. In this article, the author describes how her…

  16. SUIKERBOSRAND NATURE RESERVE

    African Journals Online (AJOL)

    Suikerbosrand Nature Reserve and fts educational facilities are run by the Transvaal. Division of. Nature Conservation. ... tion and the education facilities provided. The former are utilized mainly by the general public ... artist Paul Bosman (already reviewed in the EEASA newsletter). The co-founders of the Foundation are.

  17. European natural gas

    International Nuclear Information System (INIS)

    Thackeray, Fred

    1999-11-01

    Contains Executive Summary and Chapters on: Main issues; Natural gas consumption and supply: statistics and key features of individual countries; Sectoral natural gas consumption; Indigenous production; Imports; Prices and taxes; The spot market: The interconnector; Forecasts of production and consumption and contracted imports; Progress of markets liberalisation; Effects of environmentalist developments; Transmission networks and storage; Some principal players. (Author)

  18. Natural Ventilation in Atria

    DEFF Research Database (Denmark)

    Svidt, Kjeld; Heiselberg, Per; Hendriksen, Ole Juhl

    This case study comprises a monitoring programme as well as a Computational Fluid Dynamics (CFD) analysis of a natural ventilated atrium. The purpose has been to analyse the performance of a typical natural ventilation system in Denmark under both summer and winter conditions....

  19. Nature and landscape protection

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    In accordance with National Council of the Slovak Republic Act N. 287/1994 Coll. on Nature and Landscape Protection, the system of complex nature landscape protection has been designed based on five levels of protection. Categories of protected areas as well as cultural monuments in the Slovak Republic are reviewed.Slovak contribution to the world heritage is included

  20. Exposure to natural radiation

    International Nuclear Information System (INIS)

    Green, B.M.R.

    1985-01-01

    A brief report is given of a seminar on the exposure to enhanced natural radiation and its regulatory implications held in 1985 at Maastricht, the Netherlands. The themes of the working sessions included sources of enhanced natural radiation, parameters influencing human exposure, measurement and survey programmes, technical countermeasures, risk and assessment studies, philosophies of dose limitations and national and international policies. (U.K.)

  1. Chemistry of Natural Dyes

    Indian Academy of Sciences (India)

    The sulfonated oils, which possess better metal bind- ing capacity than the natural oils due to the presence of sulfonic acid group, bind to metal ions forming a complex with the dye to give superior fastness and hue. Limitations of Natural Dyes. Tedious extraction of colouring component from the raw mate- rial, low colour ...

  2. Archives: Sciences & Nature

    African Journals Online (AJOL)

    Items 1 - 9 of 9 ... Archives: Sciences & Nature. Journal Home > Archives: Sciences & Nature. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. 1 - 9 of 9 Items. 2011. Vol 8, No 1-2 ...

  3. Modeling Natural Selection

    Science.gov (United States)

    Bogiages, Christopher A.; Lotter, Christine

    2011-01-01

    In their research, scientists generate, test, and modify scientific models. These models can be shared with others and demonstrate a scientist's understanding of how the natural world works. Similarly, students can generate and modify models to gain a better understanding of the content, process, and nature of science (Kenyon, Schwarz, and Hug…

  4. Nature as Measure

    DEFF Research Database (Denmark)

    Peters, Terri

    2011-01-01

    The potential for biomimicry lies far beyond the direct imitation of natural forms. Guest-editor Terri Peters describes how Janine Benyus, the biologist and innovation consultant, is using biomimicry to create performance metrics from natural technologies and processes for assessing aspects...

  5. Revenge of Mother Nature

    DEFF Research Database (Denmark)

    Hansen, Kim Toft

    2018-01-01

    by employing the well-known mythical trope of the forest. This specific attention towards nature, the forest and the Swedish landscape not only establishes a supernatural sense of place and nature. While creating a generic hybrid between crime fiction and tropes and motifs from the horror genre and what has...... been dubbed ecohorror (Murray & Heumann 2016; Crosby 2014), the supernaturalisation of the landscape in both series establishes an ecocriti-cal consideration of retaliating nature reacting against human interference with nature. The visual etymology of such place sensibilities reaches back in Nordic...... landscape iconography with an obvious relationship with the notion of the Nordic sublime in romantic landscape painting (Alsen & Landmann 2016). These dramas address nature and ecocritical issues by way of a supernature with agency....

  6. Nature teaching structures

    DEFF Research Database (Denmark)

    Wester, Ture

    2002-01-01

    -living nature a number of striking statical and kinematical peculiarities have been observed. The paper will try to isolate and describe some of these observations and their relation to our engineered structures based on human thinking. The paper will deal with basic aspects as geometry, topology, redundancy...... and rare piece of fine architecture - or a common organism in Nature. That is why Nature makes an excellent object for architectural students to study structures from a conceptual and a morphological point of view. And that is why Nature - who has developed her structural systems by trial-and-error through...... millions of years - acts as an excellent teacher of these topics. At the same time, the idiom of Nature seems to possess a considerable attraction for students and is able to convey inspiration and imagination to the creative process of shaping architectural structures. In our surrounding living and non...

  7. Unnaturalised racial naturalism.

    Science.gov (United States)

    Hochman, Adam

    2014-06-01

    Quayshawn Spencer (2014) misunderstands my treatment of racial naturalism. I argued that racial naturalism must entail a strong claim, such as "races are subspecies", if it is to be a substantive position that contrasts with anti-realism about biological race. My recognition that not all race naturalists make such a strong claim is evident throughout the article Spencer reviews (Hochman, 2013a). Spencer seems to agree with me that there are no human subspecies, and he endorses a weaker form of racial naturalism. However, he supports his preferred version of 'racial naturalism' with arguments that are not well described as 'naturalistic'. I argue that Spencer offers us an unnaturalised racial naturalism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Inverse odds ratio-weighted estimation for causal mediation analysis.

    Science.gov (United States)

    Tchetgen Tchetgen, Eric J

    2013-11-20

    An important scientific goal of studies in the health and social sciences is increasingly to determine to what extent the total effect of a point exposure is mediated by an intermediate variable on the causal pathway between the exposure and the outcome. A causal framework has recently been proposed for mediation analysis, which gives rise to new definitions, formal identification results and novel estimators of direct and indirect effects. In the present paper, the author describes a new inverse odds ratio-weighted approach to estimate so-called natural direct and indirect effects. The approach, which uses as a weight the inverse of an estimate of the odds ratio function relating the exposure and the mediator, is universal in that it can be used to decompose total effects in a number of regression models commonly used in practice. Specifically, the approach may be used for effect decomposition in generalized linear models with a nonlinear link function, and in a number of other commonly used models such as the Cox proportional hazards regression for a survival outcome. The approach is simple and can be implemented in standard software provided a weight can be specified for each observation. An additional advantage of the method is that it easily incorporates multiple mediators of a categorical, discrete or continuous nature. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Humanism and nature – some reflections on a complex relationship

    Directory of Open Access Journals (Sweden)

    Jörn Rüsen

    2006-04-01

    Full Text Available The paper starts with a systematical analysis of the interrelationship of humanism and nature. It proceeds to a historical reconstruction of this relationship in the development of Western humanism from ancient Rome via Renaissance till the Enlightenment of the 18th century. In both respects the result of the analysis is the same: The Western tradition of humanism is characterised by a gap between an emphasis on the cultural quality of human life on the one hand and nature on the other one. Men are entitled to dominate and govern nature and use it for their purpose. This fits into an idea of a progressing destructive relationship between man and nature in the West. On the other the tradition of humanism has put the gap between man and nature into a harmonising cosmological or theological context. In this context a simple destructive relationship between man and nature is not possible. The humanism of today has to pick up the challenge of the ecological crisis and to refer to its tradition where man and nature are mediated into a meaningful and sense-bearing interrelationship. Instead of simply referring to the traditional cosmology a convincing idea of this mediation or even synthesis can only be made plausible by referring to the already pre-given synthesis between nature and culture, the human body.

  10. Newborn Analgesia Mediated by Oxytocin during Delivery

    Science.gov (United States)

    Mazzuca, Michel; Minlebaev, Marat; Shakirzyanova, Anastasia; Tyzio, Roman; Taccola, Giuliano; Janackova, Sona; Gataullina, Svetlana; Ben-Ari, Yehezkel; Giniatullin, Rashid; Khazipov, Rustem

    2011-01-01

    The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on newborns during delivery. Using a thermal tail-flick assay, we report that pain sensitivity is two-fold lower in rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in 2-day-old rats, whereas oxytocin reduced pain at both ages suggesting an endogenous analgesia by oxytocin during delivery. Similar analgesic effects of oxytocin, measured as attenuation of pain-vocalization induced by electrical whisker pad stimulation, were also observed in decerebrated newborns. Oxytocin reduced GABA-evoked calcium responses and depolarizing GABA driving force in isolated neonatal trigeminal neurons suggesting that oxytocin effects are mediated by alterations of intracellular chloride. Unlike GABA signaling, oxytocin did not affect responses mediated by P2X3 and TRPV1 receptors. In keeping with a GABAergic mechanism, reduction of intracellular chloride by the diuretic NKCC1 chloride co-transporter antagonist bumetanide mimicked the analgesic actions of oxytocin and its effects on GABA responses in nociceptive neurons. Therefore, endogenous oxytocin exerts an analgesic action in newborn pups that involves a reduction of the depolarizing action of GABA on nociceptive neurons. Therefore, the same hormone that triggers delivery also acts as a natural pain killer revealing a novel facet of the protective actions of oxytocin in the fetus at birth. PMID:21519396

  11. Viable supersymmetry and leptogenesis with anomaly mediation

    International Nuclear Information System (INIS)

    Ibe, Masahiro; Yanagida, Tsutomu; Kitano, Ryuichiro; Murayama, Hitoshi

    2004-01-01

    The seesaw mechanism that explains the small neutrino masses comes naturally with supersymmetric (SUSY) grand-unification and leptogenesis. However, the framework suffers from the SUSY flavor and CP problems, and has a severe cosmological gravitino problem. We propose anomaly mediation as a simple solution to all these problems, which is viable once supplemented by the D-terms for U(1) Y and U(1) B-L . Even though the right-handed neutrino mass explicitly breaks U(1) B-L and hence reintroduces the flavor problem, we show that it lacks the logarithmic enhancement and poses no threat to the framework. The thermal leptogenesis is then made easily consistent with the gravitino constraint

  12. Turgor-mediated transport of sugars

    International Nuclear Information System (INIS)

    Daie, J.

    1986-01-01

    Membrane associated processes have been suggested to be modulated by cellular turgor. The nature of this regulation is not, however, clearly understood. Evidence is presented that active but not passive transport of sugars is turgor regulated. Isolated phloem tissue, vascular bundles or storage parenchyma of celery were incubated in buffered solutions adjusted to 100, 200 or 400 m osmolal that contained various concentrations of 14 C-sugars. Cellular turgor was manipulated by using the non-permeating PEG (3350). Saturating carrier-mediated sucrose transport which is present only in phloem-containing tissue was enhanced under low turgor conditions. Sucrose diffusion, the predominant mode of uptake in non-phloem parenchyma tissue was not affected by cellular turgor. Furthermore, GA and IAA seem to interact with cellular turgor to bring about modified rates of sucrose uptake. The data are consistent with observations that sucrose loading is enhanced under mild water deficit conditions

  13. Natural product-based amyloid inhibitors.

    Science.gov (United States)

    Velander, Paul; Wu, Ling; Henderson, Frances; Zhang, Shijun; Bevan, David R; Xu, Bin

    2017-09-01

    Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Causal Mediation Analysis for the Cox Proportional Hazards Model with a Smooth Baseline Hazard Estimator.

    Science.gov (United States)

    Wang, Wei; Albert, Jeffrey M

    2017-08-01

    An important problem within the social, behavioral, and health sciences is how to partition an exposure effect (e.g. treatment or risk factor) among specific pathway effects and to quantify the importance of each pathway. Mediation analysis based on the potential outcomes framework is an important tool to address this problem and we consider the estimation of mediation effects for the proportional hazards model in this paper. We give precise definitions of the total effect, natural indirect effect, and natural direct effect in terms of the survival probability, hazard function, and restricted mean survival time within the standard two-stage mediation framework. To estimate the mediation effects on different scales, we propose a mediation formula approach in which simple parametric models (fractional polynomials or restricted cubic splines) are utilized to approximate the baseline log cumulative hazard function. Simulation study results demonstrate low bias of the mediation effect estimators and close-to-nominal coverage probability of the confidence intervals for a wide range of complex hazard shapes. We apply this method to the Jackson Heart Study data and conduct sensitivity analysis to assess the impact on the mediation effects inference when the no unmeasured mediator-outcome confounding assumption is violated.

  15. The Energy National Mediator. Activity 2008. Annual report

    International Nuclear Information System (INIS)

    2009-01-01

    This document is the first annual report published by the Energy National Mediator, an independent public institution created in 2006, the missions of which are to recommend solutions to some disputes between electricity and natural gas consumers and producers, and to inform consumers about their rights. The report presents and discusses these both missions, comments the challenges and problems the institution has faced, the approach it has adopted, notably in the relationship with producers and consumers, and the obtained results

  16. Anomalous U(1) as a mediator of Supersymmetry Breaking

    CERN Document Server

    Dvali, Gia; Dvali, Gia; Pomarol, Alex

    1996-01-01

    We point out that an anomalous gauge U(1) symmetry is a natural candida= te for being the mediator and messenger of supersymmetry breaking. It facilitate= s dynamical supersymmetry breaking even in the flat limit. Soft masses are induced by both gravity and the U(1) gauge interactions giving an unusual= mass hierarchy in the sparticle spectrum which suppresses flavor violations. T= his scenario does not suffer from the Polonyi problem.

  17. It takes a village: rural nursing preceptorships as cultural mediation

    OpenAIRE

    Zawaduk, Cheryl Ann

    2011-01-01

    In-depth interviews with five nursing students and five rural preceptors in the southern interior region of British Columbia were used to develop an ethnographically informed, multi-dimensional account of the nature and educational value of rural hospital-based preceptorships. Rather than a straightforward teacher-student or mentor-novice relationship, the reciprocity between preceptor and student was situated within a process of cultural mediation in which relationships with the healthcare t...

  18. Monocytic MDSCs regulate macrophage-mediated xenogenic cytotoxicity.

    Science.gov (United States)

    Maeda, Akira; Eguchi, Hiroshi; Nakahata, Kengo; Lo, Pei-Chi; Yamanaka, Kazuaki; Kawamura, Takuji; Matsuura, Rei; Sakai, Rieko; Asada, Mayumi; Okuyama, Hiroomi; Miyagawa, Shuji

    2015-10-01

    Xenotransplantation is considered to be one of the most attractive strategies for overcoming the worldwide shortage of organs. However, many obstructions need to be overcome before it will achieve clinical use in patients. One such obstacle is the development of an effective immunosuppressive strategy. We previously reported that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of progenitor and immature myeloid cells, suppress xenogenic CTL-mediated cytotoxicity. Because of their heterogeneous nature, MDSC can function via several suppressive mechanisms that disrupt both innate and adaptive immunity. Since macrophages play a pivotal role in the rejection of a xenograft, in this study, we evaluated the suppressive effects of MDSC against macrophage-mediated xenogenic rejection. To evaluate the effect of monocyte-derived MDSCs on xenogenic immune reactions, a CFSE(carboxyfluorescein diacetate, succinimidyl ester)assay was employed to assess cytotoxicity. While, in the absence of activation, primed MDSCs had no detectable effect on macrophage-induced cytotoxicity against SEC cells, LPS-activated MDSCs were found to significantly suppress xenogenic cytotoxicity. A CFSE cytotoxicity assay revealed that MDSCs significantly suppressed macrophage-induced cytotoxicity. Furthermore, an indoleamine 2,3 dioxygenase (IDO) inhibitor, 1-methyl tryptophan (1-MT), abolished the MDSC-induced suppression of macrophage-mediated xeno-rejection, indicating that MDSCs may suppress macrophage-mediated cytotoxicity in an IDO-dependent manner. These findings indicate that MDSCs have great potential for immunosuppressing macrophage-mediated xeno-rejection. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Almacenamiento de gas natural

    Directory of Open Access Journals (Sweden)

    Tomás Correa

    2008-12-01

    Full Text Available The largest reserves of natural gas worldwide are found in regions far of main cities, being necessary different alternatives to transport the fluid to the consumption cities, such as pipelines, CNG or ships, LNG, depending on distances between producing regions and demanding regions and the producing volumes. Consumption regions have three different markets to naturalgas; residential and commercial, industrial and power generation sector. The residential and commercial is highly seasonal and power generation sector is quite variable depending on increases of temperature during summer time. There are also external issuesthat affect the normal gas flow such as fails on the national system or unexpected interruptions on it, what imply that companies which distribute natural gas should design plans that allow supplying the requirements above mentioned. One plan is using underground natural gas storage with capacities and deliverability rates enough to supply demands. In Colombia there are no laws in this sense but it could be an exploration to discuss different ways to store gas either way as underground natural gas storage or above superficies. Existing basically three different types of underground natural gas storage; depleted reservoirs, salt caverns and aquifers. All ofthem are adequate according to geological characteristics and the needs of the distributors companies of natural gas. This paper is anexploration of technical and economical characteristics of different kind of storages used to store natural gas worldwide.

  20. Natural gas in Mexico

    International Nuclear Information System (INIS)

    Ramirez, M.

    1999-01-01

    A series of overhead viewgraphs accompanied this presentation which focused on various aspects of the natural gas industry in Mexico. Some of the viewgraphs depicted statistics from 1998 regarding natural gas throughput from various companies in North America, natural gas reserves around the world, and natural gas reserves in Mexico. Other viewgraphs depicted associated and non-associated natural gas production from 1988 to 1998 in million cubic feet per day. The Burgos Basin and the Cantarell Basin gas production from 1997 to 2004 was also depicted. Other viewgraphs were entitled: (1) gas processing infrastructure for 1999, (2) cryogenic plant at Cd. PEMEX, (3) average annual growth of dry natural gas production for 1997-2004 is estimated at 5.2 per cent, (4) gas flows for December 1998, (5) PGPB- interconnect points, (6) U.S. Mexico gas trade for 1994-1998, (7) PGPB's interconnect projects with U.S., and (8) natural gas storage areas. Technological innovations in the industry include more efficient gas turbines which allow for cogeneration, heat recovery steam generators which reduce pollutant emissions by 21 per cent, cold boxes which increase heat transfer efficiency, and lateral reboilers which reduce energy consumption and total costs. A pie chart depicting natural gas demand by sector shows that natural gas for power generation will increase from 16 per cent in 1997 to 31 per cent in 2004. The opportunities for cogeneration projects were also reviewed. The Comision Federal de Electricidad and independent power producers represent the largest opportunity. The 1997-2001 investment program proposes an 85 per cent sulphur dioxide emission reduction compared to 1997 levels. This presentation also noted that during the 1998-2001 period, total ethane production will grow by 58 tbd. 31 figs

  1. Living in cities, naturally.

    Science.gov (United States)

    Hartig, Terry; Kahn, Peter H

    2016-05-20

    Natural features, settings, and processes in urban areas can help to reduce stress associated with urban life. In this and other ways, public health benefits from, street trees, green roofs, community gardens, parks and open spaces, and extensive connective pathways for walking and biking. Such urban design provisions can also yield ecological benefits, not only directly but also through the role they play in shaping attitudes toward the environment and environmental protection. Knowledge of the psychological benefits of nature experience supports efforts to better integrate nature into the architecture, infrastructure, and public spaces of urban areas. Copyright © 2016, American Association for the Advancement of Science.

  2. EEC's: natural uramium supplies

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    The demand for nuclear fuel to supply the nuclear plants within the ECC (31,200 MW at the end of last year) totalled nearly 9,600 tons of natural uranium and 4,900 of separation work units (SWU). Once reactors currently under construction come into service, the demand for natural uranium will reach 13,200 tons by 1985 and that for SWUs to 8,600. If one takes the years 1981 to 1985, total natural uranium needs during this period will be 56,300 tons and those for SWUs 35.100 [fr

  3. Closer to Nature?

    DEFF Research Database (Denmark)

    Borkfelt, Sune; Kondrup, Sara; Röcklinsberg, Helena

    2015-01-01

    discourses in order to sell one image of animal welfare in intensive animal production while the actual production at the same time presupposes a quite different paradigm of animal welfare. Specifically, product advertising utilizes representations tied to concepts of naturalness in depictions of both animal...... lives and product processes as “natural”. Product marketing suggests a coherence between nature, production process (farm, animal), and end product, thereby creating associations that the lives of production animals are lived in nature and that their products bring a wholesome and sustainable...

  4. Structural patterns in nature

    DEFF Research Database (Denmark)

    Wester, Ture

    2003-01-01

    It seemens that some very basic randomly produced geometric/topological patterns are commonly found in Nature and have often very distinctive structural qualities. In Nature we find the same pattern in all scales from the universe to molecules, from solar systems to packing of cells, from glaciers...... to sea shells, from river systems to trees etc. Sometimes this seeming archetypical morphology involve structrual action and sometimes not-but the fact that it often posses efficient structural action opens a tool for evaluation and analysis of structures in nature and at the same time might...

  5. Structural patterns in nature

    DEFF Research Database (Denmark)

    Wester, Ture

    2004-01-01

    It seems that some very basic randomly produced geometric/topological patterns are commonly found in Nature and have often very distinctive structural qualities. In nature we find the same pattern in all scales from the universe to molecules, from solar systems to packing of cells, from glaciers...... to sea shells, from river systems to trees etc. Sometimes this seeming archetypical morphology involve structural action and sometimes not - but the fact that it often posses efficient structural action opens a tool for evaluation and analyses of structures in nature and at the same time might...

  6. The unnatural racial naturalism.

    Science.gov (United States)

    Spencer, Quayshawn

    2014-06-01

    In the recent article, "Against the New Racial Naturalism", Adam Hochman (2013, p. 332) argues that new racial naturalists have been too hasty in their racial interpretation of genetic clustering results of human populations. While Hochman makes a number of good points, the purpose of this paper is to show that Hochman's attack on new racial naturalists is misguided due to his definition of 'racial naturalism'. Thus, I will show that Hochman's critique is merely a consequence of an unnatural interpretation of racial naturalism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The mechanization of natural philosophy

    CERN Document Server

    Garber, Daniel

    2014-01-01

    This book reviews the transformation of natural philosophy in the 16th and 17th centuries: description of nature in mathematical terms; comparison of natural phenomena to existing or imaginary machines and the use of mechanical analogies in natural philosophy.

  8. Conversations Around Practice: Mediating Opportunities to Learn about Teaching Science

    Science.gov (United States)

    Ricketts, Amy Rene

    This study contributes to the knowledge base regarding the ways in which school-based, ongoing, professional learning communities mediate teacher learning. Specifically, it investigates an organic learning group as they met in various contexts over a full school year, engaging in conversations around their teaching practices that focused on supporting students' explanations of scientific phenomena. The group consisted of ten middle school science teachers from three schools in the same public school district, their district science coordinator and a professor of science education. Drawing on traditions of ethnography and discourse analysis, this case study: 1) characterizes each episode of the group's conversations around practice in terms of its potential for generating transformative learning opportunities, 2) identifies which spontaneous and designed features of those conversations accounted for differences in the generative nature of the talk, and 3) explains how those features mediated the generative nature of the talk. In this group, the differences between more- and less- generative talk could be attributed to five features: the context of the conversation; the tools participants used to represent their practice; the stance with which they represented and took up one another's practices in the talk; the resources they drew on (in terms of expertise); the conversational routines in which they engaged. These five features interacted in complex, patterned ways to mediate the generative nature of the group's talk.

  9. 15 CFR 923.54 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Mediation. 923.54 Section 923.54... Mediation. (a) Section 307(h) of the Act provides for mediation of serious disagreement between any Federal... cases, mediation by the Secretary, with the assistance of the Executive Office of the President, may be...

  10. 34 CFR 110.32 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 110.32 Section 110.32 Education Regulations..., Conciliation, and Enforcement Procedures § 110.32 Mediation. (a) ED promptly refers to the Federal Mediation and Conciliation Service or to the mediation agency designated by the Secretary of Health and Human...

  11. 38 CFR 18.543 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Mediation. 18.543 Section... Enforcement Procedures § 18.543 Mediation. (a) Referral of complaints for mediation. VA will refer to the Federal Mediation and Conciliation Service all complaints that: (1) Fall within the jurisdiction of the...

  12. 7 CFR 614.11 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mediation. 614.11 Section 614.11 Agriculture... AGRICULTURE CONSERVATION OPERATIONS NRCS APPEAL PROCEDURES § 614.11 Mediation. (a) A participant who wishes to pursue mediation must file request for mediation under this part with the NRCS official designated in the...

  13. 43 CFR 17.332 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Mediation. 17.332 Section 17.332 Public..., and Enforcement Procedures § 17.332 Mediation. (a) Referral of complaints for mediation. DOI will... participate in the mediation process to the extent necessary to reach an agreement or make an informed...

  14. Mediation and Counseling Services: A Viable Partnership

    Science.gov (United States)

    Hodges, Shannon

    2009-01-01

    Mediation has become common in many areas of society, including marital dissolution, community disputes, governmental agencies, and business and industry. Though higher education has been slower than society to adopt mediation services, campus mediation is becoming increasingly more common. This article explains why mediation is a viable…

  15. 24 CFR 146.35 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Mediation. 146.35 Section 146.35... ASSISTANCE Investigation, Settlement, and Enforcement Procedures § 146.35 Mediation. (a) HUD shall refer to the Federal Mediation and Conciliation Service, a mediation agency designated by the Secretary of...

  16. 10 CFR 1040.89-6 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Mediation. 1040.89-6 Section 1040.89-6 Energy DEPARTMENT... Enforcement Procedures § 1040.89-6 Mediation. (a) Referral of complaints for mediation. DOE will refer to the Federal Mediation and Conciliation Service, in accordance with 45 CFR 90.43(c)(3), all complaints that: (1...

  17. 15 CFR 930.111 - OCRM mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false OCRM mediation. 930.111 Section 930... FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.111 OCRM mediation. The availability of mediation does not preclude use by the parties of alternative means for...

  18. Mediation in Schools: Tapping the Potential

    Science.gov (United States)

    Hendry, Richard

    2010-01-01

    This article explores the developing role of mediation as a conflict resolution process in schools. It gives an accepted definition and clarifies the purposes of mediation, outlining the range of contexts in and beyond schools in which mediation is already offered as a formal intervention. The typical process of mediation itself is described. The…

  19. 22 CFR 218.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 218.33 Section 218.33 Foreign... § 218.33 Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and Conciliation Service all complaints that: (1) fall within the jurisdiction of these...

  20. 45 CFR 91.43 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 91.43 Section 91.43 Public Welfare... Enforcement Procedures § 91.43 Mediation. (a) HHS will promptly refer to a mediation agency designated by the... mediation process to the extent necessary to reach an agreement or make an informed judgment that an...

  1. 15 CFR 20.12 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Mediation. 20.12 Section 20.12... Procedures § 20.12 Mediation. (a) DOC will refer to a mediation service designated by the Secretary all... further processing. (b) Both the complainant and the recipient shall participate in the mediation process...

  2. 14 CFR 1252.402 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Mediation. 1252.402 Section 1252.402... Procedures § 1252.402 Mediation. (a) Referral of complaints for mediation. NASA will refer to the Federal Mediation and Conciliation Service all complaints that: (1) Fall within the jurisdiction of the Act and...

  3. 7 CFR 780.9 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Mediation. 780.9 Section 780.9 Agriculture Regulations... PROGRAMS APPEAL REGULATIONS § 780.9 Mediation. (a) Any request for mediation must be submitted after... once: (1) If resolution of an adverse decision is not achieved in mediation, a participant may exercise...

  4. 10 CFR 4.333 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Mediation. 4.333 Section 4.333 Energy NUCLEAR REGULATORY... Investigation, Conciliation, and Enforcement Procedures § 4.333 Mediation. (a) Referral of complaints for mediation. NRC will refer to a mediation agency designated by the Secretary of the Department of Health and...

  5. 45 CFR 1156.16 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Mediation. 1156.16 Section 1156.16 Public Welfare... Procedures § 1156.16 Mediation. (a) Referral of complaints for mediation. The Endowment will promptly refer all complaints to the agency designated by the Secretary of HHS to manage the mediation process that...

  6. Strongly coupled semidirect mediation of supersymmetry breaking

    International Nuclear Information System (INIS)

    Ibe, M.; Izawa, K.-I.; Nakai, Y.

    2009-01-01

    Strongly coupled semidirect gauge mediation models of supersymmetry breaking through massive mediators with standard-model charges are investigated by means of composite degrees of freedom. Sizable mediation is realized to generate the standard-model gaugino masses for a small mediator mass without breaking the standard-model symmetries.

  7. The Effects of Conflict Resolution and Peer Mediation Training on Turkish Elementary School Students' Conflict Resolution Strategies

    Science.gov (United States)

    Turnuklu, Abbas; Kacmaz, Tarkan; Gurler, Selma; Turk, Fulya; Kalender, Alper; Zengin, Feza; Sevkin, Burcak

    2010-01-01

    The effectiveness of conflict resolution and peer mediation (CRPM) training among 10- and 11-year-old elementary school students was examined. The CRPM training program consisted of skills, such as understanding the nature of interpersonal conflicts, communication, anger management, negotiation and peer mediation. The research was carried out…

  8. Natural immunity and HIV disease progression

    DEFF Research Database (Denmark)

    Ullum, H; Cozzi-Lepri, A; Aladdin, H

    1999-01-01

    OBJECTIVE: To investigate the clinical implications of impaired levels of the natural immunity mediated by natural killer (NK) cells and lymphokine activated killer (LAK) cells during infection with HIV-1. DESIGN: Data used were from 172 individuals with an estimated measure of NK cell activity...... and 146 with an estimated measure of LAK cell activity. Patients had active HIV infection at the time of enrolment in the study and have been followed-up prospectively for a median of 3.0 years. METHODS: The lytic activity of NK cells and LAK cells, the CD4 T lymphocyte count, and the concentration of CD......16/CD56 NK cells were measured at enrolment. HIV RNA in plasma was measured retrospectively. Survival analysis was performed considering three main endpoints: CD4 cell counts below 100 x 10(6) cells/l, clinical AIDS, and death. RESULTS: In unadjusted analysis and after adjustment for age, CD4 T...

  9. Boosting vaccine efficacy the natural (killer) way

    Science.gov (United States)

    Rydyznski, Carolyn E.; Waggoner, Stephen N.

    2015-01-01

    Coordination of the innate and adaptive immune systems is paramount to the development of protective humoral and cellular immunity following vaccination. Natural killer (NK) cells are front-line soldiers of the innate immune system, and recent studies have revealed functions for NK cells in long-lived immune memory and the regulation of adaptive immune responses. These findings suggest that NK cells may play important roles in the development of efficacious vaccines, as well as, in some contexts, failed immunizations. Here we review the current understanding of the immunomodulatory and memory differentiation capabilities of NK cells. We examine the context-dependency of the mechanisms and the nature NK cell-mediated modulation of the immune response, and discuss how these insights may impact immunization strategies and the development of next-generation vaccines. PMID:26272882

  10. Natural Gas Acquisition Program

    Data.gov (United States)

    General Services Administration — The "NGAP" system is a web based application which serves NGAP GSA users for tracking information details for various natural gas supply chain elements like Agency,...

  11. Vermont Designated Natural Areas

    Data.gov (United States)

    Vermont Center for Geographic Information — Under Natural Areas Law (10 Vermont Statutes Annotated, Chapter 83 � 2607) the FPR commissioner, with the approval of the governor, may designate and set aside areas...

  12. Biomimetics: nature based innovation

    National Research Council Canada - National Science Library

    Bar-Cohen, Yoseph

    2012-01-01

    "Based on the concept that nature offers numerous sources of inspiration for inventions related to mechanisms, materials, processes, and algorithms, this book covers the topic of biomimetics and the inspired innovation...

  13. Natural radioactive phon

    International Nuclear Information System (INIS)

    Birjukovs, V.; Birjukov, P.

    2004-01-01

    The natural radiating phon is determined by radioactive isotopes of elements which time of half-decay is commensurable in due course existence of the Earth, dispersing in rocks, ground, water and air, and also space radiation. (authors)

  14. Natural gas for vehicles

    International Nuclear Information System (INIS)

    Chauveron, S. de

    1996-01-01

    This article presents compressed natural gas for vehicles (CNG), which can provide considerable advantages both as an alternative fuel and as a clean fuel. These assets are not only economic but also technical. The first part deals with what is at stake in developing natural gas as a motor fuel. The first countries to use CNG were those with natural gas resources in their subsoil. Today, with a large number of countries having to cope with growing concern about increasing urban pollution, natural gas is also seen as a clean fuel that can help cut vehicle pollutant emissions dramatically. In the second part a brief technical descriptions is given of CNG stations and vehicles, with the aim of acquainting the reader with some of CNG's specific technical features as compared to gasoline and diesel oil. Here CNG technologies are seen to be very close to the more conventional ones. (author)

  15. Natural gas benefits

    International Nuclear Information System (INIS)

    1999-01-01

    The General Auditor in the Netherlands studied the natural gas policy in the Netherlands, as has been executed in the past decades, in the period 1997-1999. The purpose of the study is to inform the Dutch parliament on the planning and the backgrounds of the natural gas policy and on the policy risks with respect to the benefits for the Dutch State, taking into account the developments in the policy environment. The final conclusion is that the proposed liberalization of the national natural gas market will result in a considerable deprivation of income for the State in case the benefit policy is not adjusted. This report includes a reaction of the Dutch Minister of Economic Affairs and an afterword of the General Auditor. In the appendix an outline is given of the natural gas policy

  16. Web life: Ask Nature

    Science.gov (United States)

    2012-11-01

    Ask Nature is a site devoted to biomimicry, an interdisciplinary field in which practitioners study how animals and plants solve problems, and then use those solutions to develop better human technologies.

  17. Natural gas pricing

    International Nuclear Information System (INIS)

    Freedenthal, C.

    1993-01-01

    Natural gas pricing is the heart and soul of the gas business. Price specifically affects every phase of the industry. Too low a price will result in short supplies as seen in the mid-1970s when natural gas was scarce and in tight supply. To fully understand the pricing of this energy commodity, it is important to understand the total energy picture. In addition, the effect and impact of world and US economies, and economics in general are crucial to understanding natural gas pricing. The purpose of this presentation will be to show the parameters going into US natural gas pricing including the influence of the many outside industry factors like crude oil and coal pricing, market drivers pushing the gas industry, supply/demand parameters, risk management for buyers and sellers, and other elements involved in pricing analysis

  18. Art, Technology and Nature

    DEFF Research Database (Denmark)

    Since 1900, the connections between art and technology with nature have become increasingly inextricable. Through a selection of innovative readings by international scholars, this book presents the first investigation of the intersections between art, technology and nature in post-medieval times....... Transdisciplinary in approach, this volume’s 14 essays explore art, technology and nature’s shifting constellations that are discernible at the micro level and as part of a larger chronological pattern. Included are subjects ranging from Renaissance wooden dolls, science in the Italian art academies, and artisanal...... Camilla Skovbjerg Paldam and Jacob Wamberg trace the Kantian heritage of radically separating art and technology, and inserting both at a distance to nature, suggesting this was a transient chapter in history. Thus, they argue, the present renegotiation between art, technology and nature is reminiscent...

  19. Nature as Dissonant Heritage

    DEFF Research Database (Denmark)

    Clemmensen, Thomas Juel

    2014-01-01

    -evident. But who define and decide what kind of nature to restore? And is nature restoration not a contradiction in terms in our deeply cultivated landscapes? To examine these questions it makes sense to draw parallels between nature restoration and the concept of ‘dissonant heritage’ (Ashworth 2010), which...... concerns situations of mismatch between people and their heritage. The aim of the paper is to uncover the latent cultural dissonance in relation to nature restoration and to explain how landscape architecture could play an important role in the management of this dissonance. If one accepts that heritage...... is not the same as history, but a contemporary product shaped from history, it is clear that the same area or object could be part of different heritages, creates by different groups of people for different reasons. Heritance logically and potentially involves disinheritance – our heritage is not necessary...

  20. Natural product antifoulants

    Digital Repository Service at National Institute of Oceanography (India)

    Raveendran, T.V.; Mol, V.P.L.

    Natural Product Antifoulants (NPAs) have been proposed as one of the best replacement options for the most successful antifouling agent, tri-n-butyl tin (TBT), which, due to its ecological incompatibility, is currently facing total global ban...

  1. Breast reconstruction - natural tissue

    Science.gov (United States)

    ... After a mastectomy , some women choose to have cosmetic surgery to remake their breast. This type of surgery ... cancer - breast reconstruction with natural tissue Patient Instructions Cosmetic breast surgery - discharge Mastectomy and breast reconstruction - what to ask ...

  2. Solitonic natural orbitals

    Science.gov (United States)

    Cioslowski, Jerzy

    2018-04-01

    The dependence of the natural amplitudes of the harmonium atom in its ground state on the confinement strength ω is thoroughly investigated. A combination of rigorous analysis and extensive, highly accurate numerical calculations reveals the presence of only one positive-valued natural amplitude ("the normal sign pattern") for all ω ≥1/2 . More importantly, it is shown that unusual, weakly occupied natural orbitals (NOs) corresponding to additional positive-valued natural amplitudes emerge upon sufficient weakening of the confinement. These solitonic NOs, whose shapes remain almost invariant as their radial positions drift toward infinity upon the critical values of ω being approached from below, exhibit strong radial localization. Their asymptotic properties are extracted from the numerical data and their relevance to calculations on fully Coulombic systems is discussed.

  3. Historic Natural Vegetation

    Data.gov (United States)

    California Natural Resource Agency — In 2001, the US Fish and Wildlife Service (USFWS) and the U.S. Bureau of Reclamation (BOR) contracted with the California State University, Chico Research Foundation...

  4. Natural Gas Liquid Pipelines

    Data.gov (United States)

    Department of Homeland Security — Natural gas interstate and intrastate pipelines in the United States. Based on a variety of sources with varying scales and levels of accuracy and therefore accuracy...

  5. Is image steganography natural?

    Science.gov (United States)

    Martín, Alvaro; Sapiro, Guillermo; Seroussi, Gadiel

    2005-12-01

    Steganography is the art of secret communication. Its purpose is to hide the presence of information, using, for example, images as covers. We experimentally investigate if stego-images, bearing a secret message, are statistically "natural." For this purpose, we use recent results on the statistics of natural images and investigate the effect of some popular steganography techniques. We found that these fundamental statistics of natural images are, in fact, generally altered by the hidden "nonnatural" information. Frequently, the change is consistently biased in a given direction. However, for the class of natural images considered, the change generally falls within the intrinsic variability of the statistics, and, thus, does not allow for reliable detection, unless knowledge of the data hiding process is taken into account. In the latter case, significant levels of detection are demonstrated.

  6. Natural Hazards Image Database

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Photographs and other visual media provide valuable pre- and post-event data for natural hazards. Research, mitigation, and forecasting rely on visual data for...

  7. Natural gas supplies

    International Nuclear Information System (INIS)

    2009-10-01

    This article comments data about the share of natural gas in the energy demand in Europe, about the uses of natural gas by different sectors (housing and office buildings, electricity production, and industry) in Europe, and about gas European imports and about gas supply origins. Graphs are displaying the evolution of energy demand in some European countries between 1990 and 2006 and for different energy sources (natural gas, coal, oil, primary energy, and renewable energies), the evolution of gas production and consumption in different countries of the European Union between 1990 and 2006, and gas import origins in the European Union in 2006. Gas pipeline projects between gas producing countries and Europe are briefly presented, and the development of liquefied natural gas is briefly commented and outlined as a contribution to supply diversification

  8. Natural Gas Market Hubs

    Data.gov (United States)

    Department of Homeland Security — A hub is a physical transfer point for natural gas where several pipelines are connected. A market center is a hub where the operator offers services that facilitate...

  9. Radon - natural health threat

    International Nuclear Information System (INIS)

    Wrixon, Anthony

    1985-01-01

    Natural sources of radiation attract little attention, yet a survey has found radon gas in buildings at levels which put the occupants at some risk. The author wants safety standards set without undue delay. (author)

  10. Are Emotions Natural Kinds?

    Science.gov (United States)

    Barrett, Lisa Feldman

    2006-03-01

    Laypeople and scientists alike believe that they know anger, or sadness, or fear, when they see it. These emotions and a few others are presumed to have specific causal mechanisms in the brain and properties that are observable (on the face, in the voice, in the body, or in experience)-that is, they are assumed to be natural kinds. If a given emotion is a natural kind and can be identified objectively, then it is possible to make discoveries about that emotion. Indeed, the scientific study of emotion is founded on this assumption. In this article, I review the accumulating empirical evidence that is inconsistent with the view that there are kinds of emotion with boundaries that are carved in nature. I then consider what moving beyond a natural-kind view might mean for the scientific understanding of emotion. © 2006 Association for Psychological Science.

  11. More natural gas

    International Nuclear Information System (INIS)

    Leprince, P.; Valais, M.

    1993-01-01

    This paper reports that large resources and growing markets are the salient prospects of natural gas for the coming decades. The greater impact of natural gas on the worldwide energy market can become a reality if several scientific disciplines can be mobilized in order to succeed in cutting production costs. Modeling, mechanics of complex fluids, and physical chemistry of interfaces are basic disciplines for understanding and mastering the gas processing technologies

  12. Lesson "Balance in Nature

    Science.gov (United States)

    Chapanova, V.

    2012-04-01

    Lesson "Balance in Nature" This simulation game-lesson (Balance in Nature) gives an opportunity for the students to show creativity, work independently, and to create models and ideas. It creates future-oriented thought connected to their experience, allowing them to propose solutions for global problems and personal responsibility for their activities. The class is divided in two teams. Each team chooses questions. 1. Question: Pollution in the environment. 2. Question: Care for nature and climate. The teams work on the chosen tasks. They make drafts, notes and formulate their solutions on small pieces of paper, explaining the impact on nature and society. They express their points of view using many different opinions. This generates alternative thoughts and results in creative solutions. With the new knowledge and positive behaviour defined, everybody realizes that they can do something positive towards nature and climate problems and the importance of individuals for solving global problems is evident. Our main goal is to recover the ecological balance, and everybody explains his or her own well-grounded opinions. In this work process the students obtain knowledge, skills and more responsible behaviour. This process, based on his or her own experience, dialogue and teamwork, helps the participant's self-development. Making the model "human↔ nature" expresses how human activities impact the natural Earth and how these impacts in turn affect society. Taking personal responsibility, we can reduce global warming and help the Earth. By helping nature we help ourselves. Teacher: Veselina Boycheva-Chapanova " Saint Patriarch Evtimii" Scholl Str. "Ivan Vazov"-19 Plovdiv Bulgaria

  13. Natural gas supplies

    International Nuclear Information System (INIS)

    2009-01-01

    After having briefly commented the share of natural gas in the primary consumed energy in Europe and in France, and the reasons for its evolution, this document highlights that gas is mainly used for heating, electricity production and industrial purposes, that Europe possesses limited gas resources and must therefore rely on importations. It comments the diversification of supply sources, evokes new gas-pipeline projects between Europe and producer countries (mainly Russia), and briefly comments the development of liquefied natural gas

  14. Gaugino-assisted anomaly mediation

    International Nuclear Information System (INIS)

    Kribs, Graham D.

    2001-01-01

    I present a model of supersymmetry breaking mediated through a small extra dimension. Standard model matter multiplets and a supersymmetry-breaking (or 'hidden') sector are confined to opposite four-dimensional boundaries while gauge multiplets live in the bulk. The hidden sector does not contain a singlet and the dominant contribution to gaugino masses is via anomaly-mediated supersymmetry breaking. Scalar masses get contributions from both anomaly mediation and a tiny hard breaking of supersymmetry by operators on the hidden-sector boundary. These operators contribute to scalar masses at one loop and in most of parameter space, their contribution dominates. Thus it is easy to make all squared scalar masses positive. As no additional fields or symmetries are required below the Planck scale, this is among the simplest working models of anomaly mediation. The gaugino spectrum is left untouched and the phenomenology of the model is roughly similar to anomaly mediated supersymmetry breaking with a universal scalar mass added. Finally, the main differences in the spectrum between this model and other approaches are identified. This talk is based on work [1] done in collaboration with David E. Kaplan

  15. Natural Hazards, Second Edition

    Science.gov (United States)

    Rouhban, Badaoui

    Natural disaster loss is on the rise, and the vulnerability of the human and physical environment to the violent forces of nature is increasing. In many parts of the world, disasters caused by natural hazards such as earthquakes, floods, landslides, drought, wildfires, intense windstorms, tsunami, and volcanic eruptions have caused the loss of human lives, injury, homelessness, and the destruction of economic and social infrastructure. Over the last few years, there has been an increase in the occurrence, severity, and intensity of disasters, culminating with the devastating tsunami of 26 December 2004 in South East Asia.Natural hazards are often unexpected or uncontrollable natural events of varying magnitude. Understanding their mechanisms and assessing their distribution in time and space are necessary for refining risk mitigation measures. This second edition of Natural Hazards, (following a first edition published in 1991 by Cambridge University Press), written by Edward Bryant, associate dean of science at Wollongong University, Australia, grapples with this crucial issue, aspects of hazard prediction, and other issues. The book presents a comprehensive analysis of different categories of hazards of climatic and geological origin.

  16. The system of nature

    CERN Document Server

    D'Holbac, Baron

    1999-01-01

    "The source of Man's unhappiness is his ignorance of Nature."D'Holbach believed that the misery he saw in mankind around him was caused by religion and its superstitious beliefs - that there was a God who controlled destiny and would reward or punish individuals. The System of Nature was written to replace these delusions with a schema of understanding based solely on the physical workings of nature. "Let Man study this nature, let him learn her laws, contemplate her energies." For d'Holbach the soul is only the physical body, understood from a certain point of view, which dies when the body dies. All the events and the nature of the world can be understood in terms of the motion and properties of matter; even the tiniest causes contribute to huge events - a simple change in the diet of an Emperor (or some other such insignificant cause), he suggests might have been capable of "saving kingdoms." For him, nature's laws are fixed and necessary, and if Man wants to find happiness it is best to accept this - if g...

  17. Natural Resource Management Plan

    Energy Technology Data Exchange (ETDEWEB)

    Green, T. [Brookhaven National Laboratory (BNL), Upton, NY (United States); Schwager, K. [Brookhaven National Laboratory (BNL), Upton, NY (United States)

    2016-10-01

    This comprehensive Natural Resource Management Plan (NRMP) for Brookhaven National Laboratory (BNL) was built on the successful foundation of the Wildlife Management Plan for BNL, which it replaces. This update to the 2003 plan continues to build on successes and efforts to better understand the ecosystems and natural resources found on the BNL site. The plan establishes the basis for managing the varied natural resources located on the 5,265-acre BNL site, setting goals and actions to achieve those goals. The planning of this document is based on the knowledge and expertise gained over the past 15 years by the Natural Resources management staff at BNL in concert with local natural resource agencies including the New York State Department of Environmental Conservation, Long Island Pine Barrens Joint Planning and Policy Commission, The Nature Conservancy, and others. The development of this plan works toward sound ecological management that not only benefits BNL’s ecosystems but also benefits the greater Pine Barrens habitats in which BNL is situated. This plan applies equally to the Upton Ecological and Research Reserve (Upton Reserve). Any difference in management between the larger BNL area and the Upton Reserve are noted in the text.

  18. Three tasks for mediatization research

    DEFF Research Database (Denmark)

    Ekstrøm, Mats; Fornäs, Johan; Jansson, André

    2016-01-01

    Based on the interdisciplinary experience of a Swedish research committee, this article discusses critical conceptual issues raised by the current debate on mediatization – a concept that holds great potential to constitute a space for synthesized understandings of media-related social...... transformations. In contrast to other, more metaphorical constructions, mediatization can be studied empirically in systematic ways through various sub-processes that together provide a complex picture of how culture and everyday life evolve in times of media saturation. The first part of this article argues...... that mediatization researchers have sometimes formulated too grand claims as to mediatization’s status as a unitary approach, a meta-theory or a paradigm. Such claims have led to problematic confusions around the concept and should be abandoned in favour of a more open agenda. In line with such a call for openness...

  19. Mediation in Legal English Teaching

    Directory of Open Access Journals (Sweden)

    Chovancová Barbora

    2016-06-01

    Full Text Available Mediation is a language activity that has been unjustly neglected when preparing law students for their future professional careers. When trained in a professional context, students need to develop and improve complex communicative skills. These include not only the traditional language skills such as reading, writing, listening and speaking, but also more advanced skills such as summarizing, providing definitions, changing registers etc. All these are involved in the students’ acquisition of ‘soft skills’ that are particularly important for students of law since much of their future work involves interpersonal lawyer-client interaction. This article argues that mediation is a crucial (though previously underestimated skill and that law-oriented ESP instruction should provide training aimed at developing this skill. Showing a practical application of this approach, the paper demonstrates that mediation can be successfully integrated in the legal English syllabus and make the learning of legal English more effective.

  20. Gauge mediated mini-split

    Science.gov (United States)

    Cohen, Timothy; Craig, Nathaniel; Knapen, Simon

    2016-03-01

    We propose a simple model of split supersymmetry from gauge mediation. This model features gauginos that are parametrically a loop factor lighter than scalars, accommodates a Higgs boson mass of 125 GeV, and incorporates a simple solution to the μ- b μ problem. The gaugino mass suppression can be understood as resulting from collective symmetry breaking. Imposing collider bounds on μ and requiring viable electroweak symmetry breaking implies small a-terms and small tan β — the stop mass ranges from 105 to 108 GeV. In contrast with models with anomaly + gravity mediation (which also predict a one-loop loop suppression for gaugino masses), our gauge mediated scenario predicts aligned squark masses and a gravitino LSP. Gluinos, electroweakinos and Higgsinos can be accessible at the LHC and/or future colliders for a wide region of the allowed parameter space.

  1. Gauge mediated mini-split

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Timothy [Institute of Theoretical Science, University of Oregon,Eugene, OR 97403 (United States); Craig, Nathaniel [Department of Physics, University of California,Santa Barbara, CA 93106 (United States); Knapen, Simon [Berkeley Center for Theoretical Physics,University of California, Berkeley, CA 94720 (United States); Theoretical Physics Group,Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States)

    2016-03-15

    We propose a simple model of split supersymmetry from gauge mediation. This model features gauginos that are parametrically a loop factor lighter than scalars, accommodates a Higgs boson mass of 125 GeV, and incorporates a simple solution to the μ−b{sub μ} problem. The gaugino mass suppression can be understood as resulting from collective symmetry breaking. Imposing collider bounds on μ and requiring viable electroweak symmetry breaking implies small a-terms and small tan β — the stop mass ranges from 10{sup 5} to 10{sup 8} GeV. In contrast with models with anomaly + gravity mediation (which also predict a one-loop loop suppression for gaugino masses), our gauge mediated scenario predicts aligned squark masses and a gravitino LSP. Gluinos, electroweakinos and Higgsinos can be accessible at the LHC and/or future colliders for a wide region of the allowed parameter space.

  2. Persulfate activation by naturally occurring trace minerals.

    Science.gov (United States)

    Teel, Amy L; Ahmad, Mushtaque; Watts, Richard J

    2011-11-30

    The potential for 13 naturally occurring minerals to mediate the decomposition of persulfate and generate a range of reactive oxygen species was investigated to provide fundamental information on activation mechanisms when persulfate is used for in situ chemical oxidation (ISCO). Only four of the minerals (cobaltite, ilmenite, pyrite, and siderite) promoted the decomposition of persulfate more rapidly than persulfate-deionized water control systems. The other nine minerals decomposed persulfate at the same rate or more slowly than the control systems. Mineral-mediated persulfate activation was conducted with the addition of one of three probe compounds to detect the generation of reactive oxygen species: anisole (sulfate+hydroxyl radical), nitrobenzene (hydroxyl radical), and hexachloroethane (reductants and nucleophiles). The reduced mineral pyrite promoted rapid generation of sulfate+hydroxyl radical. However, the remainder of the minerals provided minimal potential for the generation of reactive oxygen species. The results of this research demonstrate that the majority of naturally occurring trace minerals do not activate persulfate to generate reactive oxygen species, and other mechanisms of activation are necessary to promote contaminant destruction in the subsurface during persulfate ISCO. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Linguagem, saberes e mediação sobrenatural: magia, clerezia e intervenção sobre a natureza no cotidiano e nas representações do Ocidente Medieval = Language, knowledge, and mystical mediation: magic, clergy and intervention on the nature in the quotidian and representations in Medieval West

    OpenAIRE

    Rita de Cássia Mendes Pereira

    2012-01-01

    A leitura de documentos de origem eclesiástica produzidos durante a Idade Média proporciona a impressão muito clara da presença, no cotidiano dos homens do Ocidente, de inúmeras categorias de mediadores entre o mundo natural e as forças sobrenaturais. De um lado, usando como recurso diversas formas de exercício das artes divinatórias e técnicas de manipulação de elementos da natureza, encontravam-se os magos, especialistas pretensamente dotados de saberes especiais. Às suas ações, o discurso ...

  4. Blackouts and natural risks

    Science.gov (United States)

    Danihelka, P.; Paldusová, E.; Dobeš, P.

    2009-04-01

    "Blackout" has become the common definition for the situation when electricity supply and demand are not balanced and security of supply fails. These failures have many impacts besides the lights going out, but this term is used commonly. Blackouts have drastic impacts for the society on whole and its citizens and some of them can influence big areas and last for long period, so the consequences are catastrophic. Even if at the European scale, the large extend blackouts are supposed to be exceptional, real frequency is relatively high, approximately once per two years. According to statistics, blackouts are often caused by natural causes, especially lightning. An example of lightning caused blackout is New York blackout 1977, leading to the stand-by of nuclear power plant Indian Point and with overall cost more than 300 mil. USD. There is a clear a distinction between those blackouts caused by nature and those that were caused by other faults. Usually, the nature-caused disturbances as Canada 1988, Sweden 2005 and France 1999, stay inside one country. However, their duration can extend to several weeks, and thus the costs of the interruptions and social impacts are high. Blackouts of only technologic and/or anthropogenic origin are frequently shorter, but may concern more end-users, when cascading from one country to another. Lightning is not the only natural event causing blackouts. Eighteen various case studies of blackout caused by natural events different then lightning were studied and following natural phenomenon found as a root causes: 1x forest fire, 1x snow calamity, 1x ice storm, 1x landslide, 1x high temperature, 1x geomagnetic storm, 2x earthquake, 2x inundation, 2x contact of line with trees, 6x storm (wind, hurricane…). We can conclude, that natural event are frequent cause of blackout of medium or large extend and this phenomena should be studied more in details. This contribution was supported by Ministry of Environment of the Czech Republic.

  5. Playful mediation and virtual sociality

    Directory of Open Access Journals (Sweden)

    Sihem NAJJAR

    2010-01-01

    Full Text Available As a space of sociability, virtual games, especially online role playing games, allow us to capture the interest of the playfulness in social life, but they are means by which users are able to experiment their relationship to others. The virtual games as a mediation device, constitute a "pretext" to forge friendships, develop love relationships, improve language skills, discover other cultures, etc. Based on a sociological survey of Tunisian Internet users (both sexes fans of virtual games we try to show how playful mediation is producing a multifaceted virtual sociality inherent in our contemporary societies.

  6. Family education and television mediation

    Directory of Open Access Journals (Sweden)

    Paz CÁNOVAS LEONHARDT

    2010-07-01

    Full Text Available This article try to deal with the complex influence of television viewing in the process of socialization of children and adolescents, focusing our attention on the importance of the family as the mediator-educator agency of particular relevance. Once analyzed the basic theoretical assumptions, we deepened in reality under study by providing data about how the studied population lives television and what extent parental mediation influences and affects the process. The article concludes with some reflections and pedagogical suggestions which trying to help to the optimization of the educational reality.

  7. Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

    LENUS (Irish Health Repository)

    Haase, Trutz

    2016-02-29

    A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare.

  8. Natural Dietary Phytosterols.

    Science.gov (United States)

    Racette, Susan B; Lin, Xiaobo; Ma, Lina; Ostlund, Richard E

    2015-01-01

    Most clinical phytosterol studies are performed by adding purified supplements to smaller phytosterol amounts present in the natural diet. However, natural dietary phytosterols themselves may also have important effects on cholesterol metabolism. Epidemiological work using food frequency questionnaires to estimate dietary intake suggest that extremes of normal consumption may be associated with 3-14% changes in LDL cholesterol. Standardized food databases do not have enough phytosterol values to allow calculation of phytosterol intake for individuals outside of specialized studies. Natural diets contain phytosterol amounts ranging from less than 60 mg/2000 kcal to over 500 mg/2000 kcal. Physiological studies in which whole body cholesterol metabolism is investigated show large effects of natural dietary phytosterols on cholesterol absorption efficiency, cholesterol biosynthesis and cholesterol excretion which exceed the magnitude of changes in LDL cholesterol. The dual effects of natural phytosterols on both LDL-C and whole body cholesterol metabolism need to be considered in relating them to potential protection from coronary heart disease risk.

  9. Symmetries in nature

    International Nuclear Information System (INIS)

    Mainzer, K.

    1988-01-01

    Symmetry, disymmetry, chirality etc. are well-known topics in chemistry. But they cannot only be found on the molecular level of matter. Atoms and elementary particles in physics are also characterized by particular symmetry groups. Even living organisms and populations on the macroscopic level have functional properties of symmetry. The whole physical, chemical, and biological evolution seems to be regulated by the emergence of new symmetries and the breaking down of old ones. One is reminded of Heisenberg's famous statement: 'Die letzte Wurzel der Erscheinungen ist also nicht die Materie, sondern das mathematische Gesetz, die Symmetrie, die mathematische Form' (Wandlungen in den Grundlagen der Naturwissenschaften, 1959). Historically the belief in symmetry and simplicity of nature has a long philosophical tradition from the Pythagoreans, Plato and Greek astronomers to Kepler and modern scientists. Today, 'symmetries in nature' is a common topic of mathematics, physics, chemistry, and biology. A lot of Nobel prizes were given in honour of inquiries concerning symmetries in nature. The fascination of symmetries is not only motivated by science, but by art and religion too. Therefore 'symmetris in nature' is an interdisciplinary topic which may help to overcome C.P. Snow's 'Two Cultures' of natural sciences and humanities. (author) 17 refs., 21 figs

  10. Natural gas purchasing

    International Nuclear Information System (INIS)

    Freedenthal, C.

    1993-01-01

    In recent years, natural gas has gained new momentum because of changes in marketing and regulations. The gas industry has always received an inordinate amount of regulatory control starting at the well head where the gas is produced to the consuming burner tip. Regulations have drastically impacted the availability of gas. Changes in the marketing and regulations have made the natural gas market sensitive at the point of production, the well head. Now, with plentiful supply and ease of transportation to bring the gas from the producing fields to the consumer, natural gas markets are taking advantage of the changed conditions. At the same time, new markets are developing to take advantage of the changes. This section shows consumers, especially the energy planners for large buyers of fuel, the advantages, sources and new methods of securing natural gas supplies. Background on how natural gas is produced and marketed are given. This section lists marketing sources, regulatory agencies and information groups available to help buyers and consumers of this important fuel for US industries and residences. 7 figs., 8 tabs

  11. Natural resource damage assessment

    International Nuclear Information System (INIS)

    Seddelmeyer, J.

    1991-01-01

    The assessment and collection of natural resource damages from petroleum and chemical companies unfortunate enough to have injured publicly owned natural resources is perhaps the most rapidly expanding area of environmental liability. The idea of recovering for injury to publicly owned natural resources is an extension of traditional common law tort concepts under which a person who negligently injures another or his property is called upon to compensate the injured party. Normally, once liability has been established, it is a fairly straightforward matter to calculate the various elements of loss, such as the cost to repair or replace damaged property, or medical expenses, and lost income. More difficult questions, such as the amount to be awarded for pain and suffering or emotional distress, are left to the jury, although courts limit the circumstances in which the jury is permitted to award such damages

  12. Natural gas storage

    International Nuclear Information System (INIS)

    Bautz, R.

    2009-01-01

    Storage is an important link in the natural gas supply chain. It is a valuable aid to providing the link between remote sources of production and consumption locations. After a brief recall covering the role of storage this article describes the various options for storing natural gas: saline cavities, aquifers, liquefied gas tanks or artificial cavities. A report follows on the different solutions adopted in Europe and in Switzerland, more particularly that chosen by Gaznat in order to contribute to securing supplies in Western Switzerland. Market deregulation has brought changes to the regulations, which are in turn modifying the rules that were in force until just recently, and new topics are arising, such as strategic reserves and pricing rules for stored natural gas. (author)

  13. Natural photonic crystals

    Science.gov (United States)

    Vigneron, Jean Pol; Simonis, Priscilla

    2012-10-01

    Photonic structures appeared in nature several hundred millions years ago. In the living world, color is used for communication and this important function strongly impacts the individual chances of survival as well as the chances to reproduce. This has a statistical influence on species populations. Therefore, because they are involved in evolution, natural color-generating structures are - from some point of view - highly optimized. In this short review, a survey is presented of the development of natural photonic crystal-type structures occurring in insects, spiders, birds, fishes and other marine animals, in plants and more, from the standpoint of light-waves propagation. One-, two-, and three-dimensional structures will be reviewed with selected examples.

  14. Hauntings of Human Nature

    DEFF Research Database (Denmark)

    Clasen, Mathias

    2017-01-01

    The central conflicts of Stephen King’s horror novel The Shining are rooted in human nature and reflect evolutionarily recurrent adaptive problems—the problem of balancing conflicting evolved motives, such as motives for selfish status striving versus motives for affiliative nurturing behavior...... the psychological underpinnings of the novel and the crucial function of the supernatural elements in the meaning structure of the novel. Hence we need an evolutionary psychological perspective which builds on recent findings in the sciences of human nature to account for the novel’s meaning, effects, and continued......, and the problem of surviving the hostile forces of nature. Moreover, the supernatural elements of the novel resonate with evolved intuitions about non-material, moral forces at work in the world. That is why the novel continues to engage readers worldwide. Most critics, however, have overlooked or distorted...

  15. nature in the city

    Directory of Open Access Journals (Sweden)

    Elena Grigoryeva

    2016-08-01

    The object of the issue is a wonderful museum on the Kulikovo Field designed by Sergey Gnedovsky. The unusual architecture of the new museum makes it akin to the earth’s tectonic fault caused by an intolerable tension in expectation of the battle (pp. 113-123. Oleg Yavein and Ilya Lezhava bring us back to the classic of the 20th century Mies van der Rohe and his unique dialogue with nature (pp. 162-175. Relationship between architecture and nature is a rich and limitless theme, like both of these substances. That is why the new Project Baikal issue contains, as usual, more questions than answers. Such is the nature of our journal.

  16. Down with natural selection?

    Science.gov (United States)

    Pigliucci, Massimo

    2009-01-01

    Biologists are increasingly reexamining the conceptual structure of evolutionary theory, which dates back to the so-called Modern Synthesis of the 1930s and 1940s. Calls for an Extended Evolutionary Synthesis (EES) cite a number of empirical and theoretical advances that need to be accounted for, including evolvability, evolutionary novelties, capacitors of phenotypic evolution, developmental plasticity, and phenotypic attractors. In Biological Emergences, however, Robert Reid outlines a theory of evolution in which natural selection plays no role or-worse-actually impedes evolution by what Reid calls "natural experimentation." For Reid, biological complexity emerges because of intrinsic mechanisms that work in opposition to natural selection, a view that would reopen old questions of orthogenesis and Lamarckism. This review outlines why we do need an EES, but also why it is unlikely to take the shape that Reid advocates.

  17. Nature/culture/seawater.

    Science.gov (United States)

    Helmreich, Stefan

    2011-01-01

    Seawater has occupied an ambiguous place in anthropological categories of "nature" and "culture." Seawater as nature appears as potentiality of form and uncontainable flux; it moves faster than culture - with culture frequently figured through land-based metaphors - even as culture seeks to channel water's (nature's) flow. Seawater as culture manifests as a medium of pleasure, sustenance, travel, disaster. I argue that, although seawater's qualities in early anthropology were portrayed impressionistically, today technical, scientific descriptions of water's form prevail. For example, processes of globalization - which may also be called "oceanization" - are often described as "currents," "flows," and "circulations." Examining sea-set ethnography, maritime anthropologies, and contemporary social theory, I propose that seawater has operated as a “theory machine” for generating insights about human cultural organization. I develop this argument with ethnography from the Sargasso Sea and in the Sea Islands. I conclude with a critique of appeals to water's form in social theory.

  18. Knowledge and Natural Resources

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Justinussen, Jens Christian Svabo

    2016-01-01

    Arctic economies are generally natural resource based economies, whether they are indigenous economies largely dependent on living on the land or industrialized economies depending on marine resources, mineral resources or fossil or renewable energy resources. However, the central role of knowledge...... for Arctic communities to secure local benefits and achieve sustainable development around their natural resources is often overlooked in the literature. This chapter will look at the knowledge-natural resources link for local benefits and sustainable Arctic development. For doing so, the chapter will focus...... on the Icelandic and Faroese experiences with marine resources and renewable energy resources in geothermal, hydro, tidal and wind power. Iceland and the Faroe Islands are selected because they are examples of very small Arctic societies, which particularly well illustrate how the combination of human capital...

  19. Natural gas's hottest spot

    International Nuclear Information System (INIS)

    Peterson, T.

    1993-01-01

    This paper reviews the growing power and economic strength of Enron Corp., a natural gas distributor and exploration company. The paper reviews the policy of the company to exploit deregulation at home and privatization of all sorts of energy companies abroad. Enron is actively building its own power plants in the US and has successfully boosted their profits by 20 percent in what was considered a flat natural gas market. The paper goes on to discuss the company's view of the new energy tax and how it should benefit natural gas companies as a whole. Finally the paper reviews the contracting procedures of the company to secure long-term fixed price contracts in a volatile market which precludes most companies from taking the risk

  20. Canadian natural gas

    International Nuclear Information System (INIS)

    Lucas, D.A.

    1991-01-01

    Canada's natural gas industry enjoys a quiet confidence as it looks ahead to the 1990s. In this paper, the author explains why, despite some critical uncertainties, the optimism endures. Reviewing the current conditions of supply, production, consumption, pipelines, and pipeline expansion plans, the author contends that the New World of the 1990s will belong to natural gas. The author's assessment of natural gas markets proceeds far beyond the borders of Canada. The author examines the determinants of gas prices throughout North America and he identifies the one force that promises to seize almost complete control of gas prices throughout the continent. While the analysis points out the attributes of this new pricing regime, it also names the obstacles that could prevent this emerging mechanism from assuming its anticipated position