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Sample records for cd163 mediated hemoglobin-scavenging

  1. Impaired CD163-mediated hemoglobin-scavenging and severe toxic symptoms in patients treated with gemtuzumab ozogamicin

    DEFF Research Database (Denmark)

    Maniecki, M.B.; Hasle, H.; Friis-Hansen, L.

    2008-01-01

    , and low bilirubin after septicemia-induced intravascular hemolysis indicated abrogated clearance of haptoglobin-hemoglobin complexes. This was further supported by low levels of plasma soluble CD163 and a concordant low number of CD163-expressing monocytes. We show that CD163 positive monocytes...... and macrophages from liver, spleen, and bone marrow coexpress CD33, thus suggesting that the GO-induced cellular cytotoxicity of CD33 positive cells eradicates a significant part of the CD163 positive monocytes and macrophages. The risk of severe toxic symptoms from plasma hemoglobin should be considered after CD......33-targeted chemotherapy when the disease is complicated by a pathologic intravascular hemolysis. Furthermore, the cases provide further circumstantial evidence of a key role of (CD163-expressing) monocytes/macrophages in plasma hemoglobin clearance in vivo Udgivelsesdato: 2008/8/15...

  2. The haptoglobin-CD163-heme oxygenase-1 pathway for hemoglobin scavenging

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    Thomsen, Jens Haugbølle; Etzerodt, Anders; Svendsen, Pia

    2013-01-01

    The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex...

  3. The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

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    Jens Haugbølle Thomsen

    2013-01-01

    Full Text Available The haptoglobin- (Hp- CD163-heme oxygenase-1 (HO-1 pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex in macrophages followed by lysosomal Hp-Hb breakdown and HO-1-catalyzed conversion of heme into the metabolites carbon monoxide (CO, biliverdin, and iron. The plasma concentration of Hp is a limiting factor as evident during accelerated hemolysis, where the Hp depletion may cause serious Hb-induced toxicity and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6, but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway in the anti-inflammatory response.

  4. CD163-L1 is an endocytic macrophage protein strongly regulated by mediators in the inflammatory response

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    Moeller, Jesper B; Nielsen, Marianne J; Reichhardt, Martin P

    2012-01-01

    CD163-L1 belongs to the group B scavenger receptor cysteine-rich family of proteins, where the CD163-L1 gene arose by duplication of the gene encoding the hemoglobin scavenger receptor CD163 in late evolution. The current data demonstrate that CD163-L1 is highly expressed and colocalizes with CD163...... on large subsets of macrophages, but in contrast to CD163 the expression is low or absent in monocytes and in alveolar macrophages, glia, and Kupffer cells. The expression of CD163-L1 increases when cultured monocytes are M-CSF stimulated to macrophages, and the expression is further increased by the acute......-phase mediator IL-6 and the anti-inflammatory mediator IL-10 but is suppressed by the proinflammatory mediators IL-4, IL-13, TNF-α, and LPS/IFN-γ. Furthermore, we show that CD163-L1 is an endocytic receptor, which internalizes independently of cross-linking through a clathrin-mediated pathway. Two cytoplasmic...

  5. The macrophage scavenger receptor (CD163): a double-edged sword in treatment of malignant disease

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan

    2009-01-01

    of inflammatory processes. The receptor is expressed by circulatory monocytes and it is highly expressed on tissue-resident macrophages. CD163 is also expressed on leukemic blast cells of AML type M4/M5 and tumor cells in malignant melanoma and breast cancer. Although circumstantial evidence of the potential...... was investigated in biopsies from bladder cancer patients. We demonstrated that CD163 mRNA expression was significantly elevated in muscle invasive tumors (T2-T4) compared with superficial tumors (Ta), and that a high level of CD163 mRNA expression in tumor biopsies was significantly associated with poor 13-year......The hemoglobin scavenger receptor CD163 is a transmembrane glycoprotein belonging to the scavenger receptor cysteine-rich (SRCR) domain family. It mediates the clearance of hemoglobin released to the circulation during intravascular hemolysis, and it is also involved in the regulation...

  6. Soluble CD163

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    Møller, Holger J

    2012-01-01

    CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function o...

  7. CD163 and its role in inflammation

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    Lech Chyczewski

    2011-10-01

    Full Text Available Mononuclear phagocytes represent a heterogeneous population of cells with individual subpopulations exerting different pro- or anti-inflammatory functions. CD163 is a monocyte/macrophage specific marker expressed predominantly on cells which possess strong anti-inflammatory potential. The expression of CD163 is strongly induced by anti-inflammatory mediators such as glucocorticoids and interleukin-10, while being inhibited by pro-inflammatory mediators such as interferon-gamma. CD163-expressing mononuclear phagocytes, as well as soluble CD163, may both take part in downregulating an inflammatory response. It seems, therefore, that CD163 may be an interesting target for therapeutic modulation of the inflammatory response. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 3, 365–374

  8. Haptoglobin and CD163

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    Madsen, M; Graversen, Jonas Heilskov; Moestrup, S K

    2001-01-01

    The plasma protein haptoglobin and the endocytic hemoglobin receptor HbSR/CD163 are key molecules in the process of removing hemoglobin released from ruptured erythrocytes. Hemoglobin in plasma is instantly bound with high affinity to haptoglobin--an interaction leading to the recognition of the ...

  9. Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Peterslund, Niels Anker; Graversen, Jonas Heilskov

    2002-01-01

    enabled identification of a soluble plasma form of HbSR (sHbSR) having an electrophoretic mobility equal to that of recombinant HbSR consisting of the extracellular domain (scavenger receptor cysteine-rich 1-9). A sandwich enzyme-linked immunosorbent assay was established and used to measure the s...... a level of sHbSR above the range of healthy persons. Patients with myelomonocytic leukemias and pneumonia/sepsis exhibited the highest levels (up to 67.3 mg/L). In conclusion, sHbSR is an abundant plasma protein potentially valuable in monitoring patients with infections and myelomonocytic leukemia....

  10. Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

    Science.gov (United States)

    Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; Mazur, Steven; Deiuliis, Nicole M; Radoshitzky, Sheli R; Lackemeyer, Matthew G; McCluskey, Adam; Robinson, Phillip J; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L; Lauck, Michael; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

    2015-01-01

    Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin

  11. Lesional accumulation of CD163-expressing cells in the gut of patients with inflammatory bowel disease.

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    Eleonora Franzè

    Full Text Available Monocytes/macrophages displaying different markers of activation/differentiation infiltrate the inflamed gut of patients with inflammatory bowel diseases (IBD, but the role that each monocyte/macrophage subpopulation plays in the pathogenesis of IBD is not fully understood. The hemoglobin scavenger receptor CD163, a specific marker of monocytes/macrophages, has been associated with either anti-inflammatory or inflammatory functions of macrophages in several pathologies. In this study we examined the tissue distribution and function of CD163-expressing monocytes/macrophages in IBD. CD163 RNA and protein expression was more pronounced in IBD in comparison to normal controls, with no significant difference between Crohn's disease and Ulcerative colitis. In IBD, over-expression of CD163 was restricted to areas with active inflammation and not influenced by current therapy. Immunohistochemical analysis confirmed the accumulation of CD163-expressing cells in IBD, mostly around and inside blood vessels, thus suggesting that these cells are partly recruited from the systemic circulation. Indeed, FACS analysis of circulating mononuclear cells showed that the fractions of CD163-positive monocytes were increased in IBD patients as compared to controls. Functionally, interleukin-6 up-regulated CD163 expression in lamina propria mononuclear cells and mucosal explants of normal subjects. In IBD blood and mucosal cell cultures, cross-linking of CD163 with a specific monoclonal anti-CD163 antibody enhanced tumor necrosis factor-α synthesis. These findings indicate that IBD mucosa is abundantly infiltrated with CD163-positive cells, which could contribute to amplify the inflammatory cytokine response.

  12. The macrophage scavenger receptor CD163

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    Nielsen, Marianne Jensby; Madsen, Mette; Møller, Holger J

    2006-01-01

    CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are subs......CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants...

  13. The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Aristoteli, Lina Panayiota; Møller, Holger Jon; Bailey, Brian

    2006-01-01

    BACKGROUND: CD163 is a monocyte-macrophage lineage specific scavenger receptor that mediates the uptake and clearance of haptoglobin-haemoglobin complexes, and soluble CD163 (sCD163) is also present in plasma. As atherosclerosis involves infiltration by monocyte-derived macrophages, we investigated...... whether sCD163 may act as a marker of coronary atherosclerosis (CAD). METHODS AND RESULTS: Clinical features were identified and plasma was collected from 147 consecutive patients presenting for coronary angiography. Patients were classified as having CAD+, or being free of CAD- haemodynamically...

  14. Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis

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    Greisen, Stinne Ravn; Møller, Holger Jon; Stengaard-Pedersen, Kristian

    2015-01-01

    OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease where TNF-α is a central mediator of inflammation, and is cleaved from the cell surface by TACE/ADAM17. This metalloproteinase is also responsible for the release of soluble (s) CD163. Soluble CD163 reflects macrophage activati...

  15. Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Greisen, Stinne Ravn; Møller, Holger Jon; Stengaard-Pedersen, Kristian

    2015-01-01

    OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease where TNF-α is a central mediator of inflammation, and is cleaved from the cell surface by TACE/ADAM17. This metalloproteinase is also responsible for the release of soluble (s) CD163. Soluble CD163 reflects macrophage activation...

  16. Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of 'soluble CD163' in plasma

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    Etzerodt, Anders; Berg, Ronan M.G.; Plovsing, Ronni R.

    2017-01-01

    CD163 is the macrophage receptor for uptake of hemoglobin-haptoglobin complexes. The human receptor can be shed from the macrophage surface owing to a cleavage site for the inflammation-inducible TACE/ADAM17 enzyme. Accordingly, plasma â €soluble CD163' (sCD163) has become a biomarker for macroph......CD163 is the macrophage receptor for uptake of hemoglobin-haptoglobin complexes. The human receptor can be shed from the macrophage surface owing to a cleavage site for the inflammation-inducible TACE/ADAM17 enzyme. Accordingly, plasma â €soluble CD163' (sCD163) has become a biomarker...

  17. Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Greisen, Stinne Ravn; Møller, Holger Jon; Stengaard-Pedersen, Kristian

    2015-01-01

    OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease where TNF-α is a central mediator of inflammation, and is cleaved from the cell surface by TACE/ADAM17. This metalloproteinase is also responsible for the release of soluble (s) CD163. Soluble CD163 reflects macrophage activation...... in macrophage activity as evidenced by increasing levels following anti-TNF withdrawal, despite maintenance of a stable clinical condition achieved by conventional remedies. It remains to be determined whether sCD163 is an early predictor of disease flare....

  18. Soluble CD163 levels in children with sickle cell disease

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    Møller, Holger Jon; Nielsen, Marianne Jensby; Bartram, Jack

    2011-01-01

    Sickle cell disease (SCD) is characterized by vasculopathy, which has been causally linked to intravascular haemolysis and high levels of free plasma haemoglobin. Soluble CD163 (sCD163) is implicated in the clearance of free plasma haemoglobin and high plasma concentrations have been linked to ar...

  19. CD163 positive subsets of blood dendritic cells

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    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

    2006-01-01

    CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important...... for internalization of CD91-targeted antigens to be presented on the dendritic cell surface for T-cell stimulation. Despite their overlap in functionality, the expression of CD91 and CD163 has never been compared and the expression of CD163 in the monocyte-dendritic cell lineage is not yet characterized. CD163...... expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...

  20. Urinary Soluble CD163 in Active Renal Vasculitis.

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    O'Reilly, Vincent P; Wong, Limy; Kennedy, Claire; Elliot, Louise A; O'Meachair, Shane; Coughlan, Alice Marie; O'Brien, Eoin C; Ryan, Michelle M; Sandoval, Diego; Connolly, Emma; Dekkema, Gerjan J; Lau, Jiaying; Abdulahad, Wayel H; Sanders, Jan-Stephan F; Heeringa, Peter; Buckley, Colm; O'Brien, Cathal; Finn, Stephen; Cohen, Clemens D; Lindemeyer, Maja T; Hickey, Fionnuala B; O'Hara, Paul V; Feighery, Conleth; Moran, Sarah M; Mellotte, George; Clarkson, Michael R; Dorman, Anthony J; Murray, Patrick T; Little, Mark A

    2016-09-01

    A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV. Copyright © 2016 by the American Society of Nephrology.

  1. Scavenger Receptor CD163 and Its Biological Functions

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    Gabriela Onofre

    2009-01-01

    Full Text Available CD163 is a member of scavenger receptor super family class B of the first subgroup. It is mapped to the region p13 on chromosome 12. Five different isoforms of CD163 have been described, which differ in the structure of their cytoplasmic domains and putative phosporylation sites. This scavenger receptor is selectively expressed on cells of monocytes and macrophages lineage exclusively. CD163 immunological function is essentially homeostatic. It also has other functions because participates in adhesion to endothelial cells, in tolerance induction and tissues regeneration. Other very important function of CD163 is the clearance of hemoglobin in its cell-free form and participation in anti-inflammation in its soluble form, exhibiting cytokine-like functions. We review the biological functions of CD163 which have been discovered until now. It seems apparent from this review that CD163 scavenger receptor can be used as biomarker in different diseases and as a valuable diagnostic parameter for prognosis of many diseases especially inflammatory disorders and sepsis.

  2. The macrophage scavenger receptor CD163

    NARCIS (Netherlands)

    Fabriek, Babs O.; Dijkstra, Christine D.; van den Berg, Timo K.

    2005-01-01

    Mature tissue macrophages form a first line of defense to recognize and eliminate potential pathogens; these specialized cells are capable of phagocytosis, degradation of self and foreign materials, establishment of cell-cell interactions, and the production of inflammatory mediators. Mature tissue

  3. Soluble CD163, a product of monocyte/macrophage activation, is inversely associated with haemoglobin levels in placental malaria.

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    Caroline Lin Lin Chua

    Full Text Available In Plasmodium falciparum malaria, activation of monocytes and macrophages (monocytes/macrophages can result in the production of various inflammatory mediators that contribute to immunopathology. Soluble CD163 (sCD163 is a specific marker of monocyte/macrophage activation typically found at increased levels during various inflammatory conditions and can be associated with poor clinical outcomes. To better understand the relationships between levels of sCD163 and clinical parameters in women with placental malaria, we measured plasma sCD163 levels in maternal peripheral and placental blood compartments at delivery and determined their correlations with birth weight and maternal haemoglobin concentrations. sCD163 levels were negatively correlated with birth weight only in the placental compartment (r = -0.145, p = 0.03 and were inversely correlated with maternal haemoglobin concentrations, both in peripheral blood (r = -0.238, p = 0.0004 and in placental blood (r = -0.259, p = 0.0001. These inverse relationships suggest a potential role for monocyte/macrophage activation in the pathogenesis of malaria in pregnancy, particularly in relation to malaria-associated anaemia.

  4. Drug Trafficking into Macrophages via the Endocytotic Receptor CD163

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    Graversen, Jonas Heilskov; Moestrup, Søren Kragh

    2015-01-01

    for cytotoxic or phenotype-modulating drugs in the treatment of inflammatory and cancerous diseases. Such targeting of macrophages has been tried using the natural propensity of macrophages to non-specifically phagocytose circulating foreign particulate material. In addition, the specific targeting...... of macrophage-expressed receptors has been used in order to obtain a selective uptake in macrophages and reduce adverse effects of off-target delivery of drugs. CD163 is a highly expressed macrophage-specific endocytic receptor that has been studied for intracellular delivery of small molecule drugs...... to macrophages using targeted liposomes or antibody drug conjugates. This review will focus on the biology of CD163 and its potential role as a target for selective macrophage targeting compared with other macrophage targeting approaches....

  5. Monocyte/macrophage-derived soluble CD163: A novel biomarker in multiple myeloma

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    Andersen, Morten Nørgaard; Abildgaard, Niels; Maniecki, Maciej B

    2014-01-01

    fluids (soluble CD163, sCD163). In this study, we examined serum sCD163 as a biomarker in patients with newly diagnosed multiple myeloma. METHODS: Peripheral blood (n = 104) and bone marrow (n = 17) levels of sCD163 were measured using an enzyme-linked immunosorbent assay. RESULTS: At diagnosis, high s......CD163 was associated with higher stage according to the International Staging System (ISS) and with other known prognostic factors in multiple myeloma (creatinine, C-reactive protein, and beta-2 microglobulin). Soluble CD163 decreased upon high-dose treatment, and in a multivariate survival analysis...... in bone marrow samples than in the matched blood samples, which indicate a localized production of sCD163 within the bone marrow microenvironment. CONCLUSIONS: Soluble CD163 was found to be a prognostic marker in patients with multiple myeloma. This may indicate that macrophages and/or monocytes have...

  6. Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple sclerosis

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    Fabriek, Babs O; Møller, Holger J; Vloet, Rianka P M

    2007-01-01

    The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP...

  7. Reduced sTWEAK and increased sCD163 levels in HIV-infected patients: modulation by antiretroviral treatment, HIV replication and HCV co-infection.

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    Luis M Beltrán

    Full Text Available Patients infected with the human immunodeficiency virus (HIV have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV.The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII and endothelial dysfunction (sVCAM-1 and ADMA in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART and 23 healthy subjects.Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations.HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.

  8. The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

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    Thomsen, Henrik Holm; Møller, Holger Jon; Trolle, Christian

    2013-01-01

    Soluble CD163 (sCD163) is a novel marker linked to states of low grade inflammation such as diabetes, obesity, liver disease and atherosclerosis, all prevalent in subjects with Turner and Klinefelter Syndromes. We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards...

  9. Hemoglobin induces monocyte recruitment and CD163-macrophage polarization in abdominal aortic aneurysm

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    Rubio-Navarro, Alfonso; Amaro Villalobos, Juan Manuel; Lindholt, Jes S

    2015-01-01

    BACKGROUND: Increased hemoglobin (Hb) accumulation was reported in abdominal aortic aneurysms (AAAs). CD163 is a macrophage receptor involved in tissue Hb clearance, however its role in AAA has not been reported. We investigated the role of Hb on monocyte recruitment and differentiation towards CD......163 expressing macrophages ex vivo, in vitro and in human AAA. METHODS AND RESULTS: CD163 mRNA and protein expression was significantly higher in human AAA (n=7) vs. healthy wall (n=6). CD163 was predominantly found in adventitia of AAA, coinciding with areas rich in hemosiderin and adjacent...

  10. Serum soluble CD163 predicts risk of type 2 diabetes in the general population

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    Møller, Holger Jon; Frikke-Schmidt, Ruth; Moestrup, Søren

    2011-01-01

    Activation of adipose tissue macrophages with concomitant low-grade inflammation is believed to play a central role in the development of type 2 diabetes. We tested whether a new macrophage-derived biomarker, soluble CD163 (sCD163), identifies at-risk individuals before overt disease has developed....

  11. CD163 promotes hematoma absorption and improves neurological functions in patients with intracerebral hemorrhage

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    Wen-jing Xie

    2016-01-01

    Full Text Available Clinical outcomes are positively associated with hematoma absorption. The monocyte-macrophage scavenger receptor, CD163, plays an important role in the metabolism of hemoglobin, and a soluble form of CD163 is present in plasma and other tissue fluids; therefore, we speculated that serum CD163 affects hematoma absorption after intracerebral hemorrhage. Patients with intracerebral hemorrhage were divided into high- and low-level groups according to the average CD163 level (1,977.79 ± 832.91 ng/mL. Compared with the high-level group, the low-level group had a significantly slower hematoma absorption rate, and significantly increased National Institutes of Health Stroke Scale scores and modified Rankin Scale scores. These results suggest that CD163 promotes hematoma absorption and the recovery of neurological function in patients with intracerebral hemorrhage.

  12. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

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    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. The absence of the CD163 receptor has distinct temporal influences on intracerebral hemorrhage outcomes

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    Leclerc, Jenna L; Lampert, Andrew S; Loyola Amador, Claudia

    2018-01-01

    was induced in wildtype and CD163(-/-) mice and various anatomical and functional outcomes were assessed. At 3 d, CD163(-/-) mice have 43.4 ± 5.0% (p = 0.0002) and 34.8 ± 3.4% (p = 0.0003) less hematoma volume and tissue injury, respectively. Whereas, at 10 d, CD163(-/-) mice have 49.2 ± 15.0% larger lesions...

  14. Plasma level of the macrophage-derived soluble CD163 is increased and positively correlates with severity in Gaucher's disease

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    Møller, Holger Jon; de Fost, Maaike; Aerts, Hans

    2004-01-01

    Recently, soluble CD163 (sCD163) has been identified as a macrophage/monocyte-specific plasma protein and increased concentrations have been measured in patients with infection and myeloid leukaemia. In the present study we investigated the levels of sCD163 in patients with Gaucher's disease...

  15. Serum soluble CD163 predicts risk of type 2 diabetes in the general population

    DEFF Research Database (Denmark)

    Møller, Holger J; Frikke-Schmidt, Ruth; Moestrup, Søren K

    2011-01-01

    has developed. METHODS: A prospective cohort study of 8849 study participants from the general population, the Copenhagen City Heart Study, was followed for 18 years for incidence of type 2 diabetes. Risk of disease was calculated according to age- and sex-adjusted percentile categories of serum s......BACKGROUND: Activation of adipose tissue macrophages with concomitant low-grade inflammation is believed to play a central role in the development of type 2 diabetes. We tested whether a new macrophage-derived biomarker, soluble CD163 (sCD163), identifies at-risk individuals before overt disease......CD163 concentrations: 0%-33%, 34%-66%, 67%-90%, 91%-95%, and 96%-100%. RESULTS: A total of 568 participants developed type 2 diabetes. The cumulative incidence increased with increasing baseline sCD163 (trend P

  16. Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery

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    Kazankov, Konstantin; Tordjman, Joan; Møller, Holger Jon

    2015-01-01

    BACKGROUND AND AIMS: Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS...... (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed. RESULTS: sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS ...). METHODS: Demographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score...

  17. Elevated soluble CD163 plasma levels are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

    Directory of Open Access Journals (Sweden)

    Junning Wang

    Full Text Available Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS. Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163. The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001. The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001. A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further.

  18. Soluble CD163 predicts incident chronic lung, kidney and liver disease in HIV infection

    DEFF Research Database (Denmark)

    Kirkegaard-Klitbo, Ditte M; Mejer, Niels; Knudsen, Troels B

    2017-01-01

    OBJECTIVE: To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma-soluble CD163 (sCD163) and incident non-AIDS comorbidities in well treated HIV-infected individuals. DESIGN: Prospective single...... was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates. RESULTS: In HIV-1-infected individuals (n = 799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease [adjusted hazard ratio (aHR), 3.2; 95% confidence interval (CI): 1.34; 7.......46] and incident chronic kidney disease (aHR, 10.94; 95% CI: 2.32; 51.35), when compared with lowest quartiles. Further, (every 1 mg) increase in plasma sCD163 was positively correlated with incident liver disease (aHR, 1.12; 95% CI: 1.05; 1.19). The sCD163 level was not associated with incident cancer...

  19. Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163

    DEFF Research Database (Denmark)

    Møller, Holger Jon; K. Moestrup, Søren; Weis, Nina Margrethe

    2006-01-01

    OBJECTIVE: Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients...... analyses at the time of first positive blood culture. MEASUREMENTS AND MAIN RESULTS: sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p ..., all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients...

  20. The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor

    DEFF Research Database (Denmark)

    Fabriek, Babs O; Polfliet, Machteld M J; Vloet, Rianka P M

    2007-01-01

    Erythropoiesis occurs in erythroblastic islands, where developing erythroblasts closely interact with macrophages. The adhesion molecules that govern macrophage-erythroblast contact have only been partially defined. Our previous work has implicated the rat ED2 antigen, which is highly expressed...... on the surface of macrophages in erythroblastic islands, in erythroblast binding. In particular, the monoclonal antibody ED2 was found to inhibit erythroblast binding to bone marrow macrophages. Here, we identify the ED2 antigen as the rat CD163 surface glycoprotein, a member of the group B scavenger receptor...... that it enhanced erythroid proliferation and/or survival, but did not affect differentiation. These findings identify CD163 on macrophages as an adhesion receptor for erythroblasts in erythroblastic islands, and suggest a regulatory role for CD163 during erythropoiesis....

  1. Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Kazankov, Konstantin; Rode, Anthony; Simonsen, Kira Schreiner

    2016-01-01

    BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a co...

  2. Anti-CD163-dexamethasone conjugate inhibits the acute phase response to lipopolysaccharide in rats

    DEFF Research Database (Denmark)

    Thomsen, Karen Louise; Møller, Holger Jon; Graversen, Jonas Heilskov

    2016-01-01

    ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight (421 ± 11 mg vs 465 ± 12 mg, P any other group. CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased...

  3. Fasting serum soluble CD 163 predicts risk of type 2 diabetes in ...

    African Journals Online (AJOL)

    grade inflammation is believed to play a central role in the evolution of type 2 diabetes. Aim: To assess whether a new macrophage-derived biomarker, soluble CD163, identifies at-risk individuals with metabolic syndrome before overt disease ...

  4. The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria

    NARCIS (Netherlands)

    Fabriek, Babs O.; van Bruggen, Robin; Deng, Dong Mei; Ligtenberg, Antoon J. M.; Nazmi, Kamran; Schornagel, Karin; Vloet, Rianka P. M.; Dijkstra, Christine D.; van den Berg, Timo K.

    2009-01-01

    The plasma membrane glycoprotein receptor CD163 is a member of the scavenger receptor cystein-rich (SRCR) superfamily class B that is highly expressed on resident tissue macrophages in vivo. Previously, the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes and to

  5. The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria

    NARCIS (Netherlands)

    Fabriek, B.O.; van Bruggen, R.; Deng, D.M.; Ligtenberg, A.J.M.; Nazmi, K.; Schornagel, K.; Vloet, R.P.M.; Dijkstra, C.D.; van den Berg, T.K.

    2009-01-01

    The plasma membrane glycoprotein re- ceptor CD163 is a member of the scaven- ger receptor cystein-rich (SRCR) super- family class B that is highly expressed on resident tissue macrophages in vivo. Pre- viously, the molecule has been shown to act as a receptor for hemoglobin- haptoglobin complexes

  6. Preterm delivery predicted by soluble CD163 and CRP in women with symptoms of preterm delivery

    DEFF Research Database (Denmark)

    Vogel, Ida; Grove, Jakob; Thorsen, Poul

    2005-01-01

    : High levels of sCD163 or CRP are associated with an increased risk of preterm delivery in women with symptoms of delivery. Good prediction of preterm delivery before 34 weeks of gestation was obtained by a combination of preterm prelabour rupture of membranes (PPROM), overweight, relaxin, CRP and s...

  7. Macrophage-related serum biomarkers soluble CD163 (sCD163) and soluble mannose receptor (sMR) to differentiate mild liver fibrosis from cirrhosis in patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Andersen, E S; Rødgaard-Hansen, S; Moessner, B

    2014-01-01

    Macrophages regulate the fibrotic process in chronic liver disease. The aim of the present pilot study was to evaluate two new macrophage-specific serum biomarkers [soluble CD163 (sCD163) and soluble mannose receptor (sMR, sCD206)] as potential fibrosis markers in patients chronically infected wi...

  8. Monocyte expression and soluble levels of the haemoglobin receptor (CD163/sCD163 and the mannose receptor (MR/sMR in septic and critically ill non-septic ICU patients.

    Directory of Open Access Journals (Sweden)

    Anders G Kjærgaard

    Full Text Available BACKGROUND: The diagnosis of sepsis is challenging and there is an unmet need for sensitive and specific diagnostic and prognostic biomarkers. Following activation of macrophages and monocytes, the haptoglobin-haemoglobin receptor (CD163 and the mannose receptor (MR are shed into the circulation (sCD163 and sMR. OBJECTIVE: We investigated monocyte expression of CD163 and MR, and levels of sCD163 and sMR in septic and non-septic patients, and in healthy controls. We hypothesised that these receptors are elevated during sepsis and can be used diagnostic and prognostic. METHODS: Twenty-one patients with severe sepsis or septic shock and 15 critically ill non-septic patients were included in this prospective observational study at three ICUs at Aarhus University Hospital and Randers Regional Hospital, Denmark. Fifteen age- and gender-matched healthy volunteers served as controls. Levels of sCD163 and sMR were measured using a sandwich ELISA and monocyte expression of CD163 and MR was evaluated by flow cytometry during the first four days of ICU stay. The diagnostic and prognostic values of the receptors were assessed using AUROC curves. RESULTS: At ICU admission and during the observation period, monocyte expression of CD163 and levels of sCD163 and sMR were significantly higher in septic patients compared with non-septic patients and healthy controls (p<0.01 for all comparisons. Monocytes did not express MR. The diagnostic values estimated by AUROC were 1.00 for sMR, 0.95 for sCD163, 0.87 for CRP, and 0.75 for monocyte-bound CD163. Among the septic patients, monocyte expression of CD163 was higher in non-survivors compared with survivors at ICU admission (p = 0.02 and during the observation period (p = 0.006. The prognostic value of monocyte-bound CD163 estimated by AUROC at ICU admission was 0.82. CONCLUSION: The macrophage-specific markers CD163, sCD163, and sMR are increased in septic patients. Particularly sMR is a promising new

  9. The identification of CD163 expressing phagocytic chondrocytes in joint cartilage and its novel scavenger role in cartilage degradation.

    Directory of Open Access Journals (Sweden)

    Kai Jiao

    Full Text Available BACKGROUND: Cartilage degradation is a typical characteristic of arthritis. This study examined whether there was a subset of phagocytic chondrocytes that expressed the specific macrophage marker, CD163, and investigated their role in cartilage degradation. METHODS: Cartilage from the knee and temporomandibular joints of Sprague-Dawley rats was harvested. Cartilage degradation was experimentally-induced in rat temporomandibular joints, using published biomechanical dental methods. The expression levels of CD163 and inflammatory factors within cartilage, and the ability of CD163(+ chondrocytes to conduct phagocytosis were investigated. Cartilage from the knees of patients with osteoarthritis and normal cartilage from knee amputations was also investigated. RESULTS: In the experimentally-induced degrading cartilage from temporomandibular joints, phagocytes were capable of engulfing neighboring apoptotic and necrotic cells, and the levels of CD163, TNF-α and MMPs were all increased (P0.05. CD163(+ chondrocytes were found in the cartilage mid-zone of temporomandibular joints and knee from healthy, three-week old rats. Furthermore, an increased number of CD163(+ chondrocytes with enhanced phagocytic activity were present in Col-II(+ chondrocytes isolated from the degraded cartilage of temporomandibular joints in the eight-week experimental group compared with their age-matched controls. Increased number with enhanced phagocytic activity of CD163(+ chondrocytes were also found in isolated Col-II(+ chondrocytes stimulated with TNF-α (P<0.05. Mid-zone distribution of CD163(+ cells accompanied with increased expression of CD163 and TNF-α were further confirmed in the isolated Col-II(+ chondrocytes from the knee cartilage of human patients with osteoarthritis, in contrast to the controls (both P<0.05. CONCLUSIONS: An increased number of CD163(+ chondrocytes with enhanced phagocytic activity were discovered within degraded joint cartilage, indicating a

  10. Soluble CD163 from activated macrophages predicts mortality in acute liver failure

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Grønbaek, Henning; Schiødt, Frank V

    2007-01-01

    .2-54.0) vs. 14.6mg/l (3.5-67.2), respectively (p=0.0025). Patients that were transplanted had intermediate levels. Sensitivity and specificity at a cut-off level of 26mg/l was 62% and 81%, respectively. CONCLUSIONS: Activated macrophages are involved in ALF resulting in a 10-fold increase in sCD163. A high...

  11. Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin

    DEFF Research Database (Denmark)

    Knudsen, Troels Bygum; Larsen, Klaus; Kristiansen, Thomas Birk

    2007-01-01

    CD163. However, sCD163 may be helpful in rapid identification of patients with systemic bacterial infection. If used as an adjunct to lumbar puncture, PCT and CRP had very high diagnostic accuracy for distinguishing between bacterial and viral infection in patients with spinal fluid pleocytosis. However......-operating characteristic AUCs (areas under curves). Patients were classified by 2 sets of diagnostic criteria into: A) purulent meningitis, serous meningitis or non-meningitis, and B) systemic bacterial infection, local bacterial infection or non-bacterial disease. An elevated serum level of sCD163 was the most specific......The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected...

  12. Macrophage activation marker sCD163 correlates with accelerated lipolysis following LPS exposure: a human-randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Nikolaj Rittig

    2018-01-01

    Full Text Available Background: Macrophage activation determined by levels of soluble sCD163 is associated with obesity, insulin resistance, diabetes mellitus type 2 (DM2 and non-alcoholic fatty liver disease (NAFLD. This suggests that macrophage activation is involved in the pathogenesis of conditions is characterised by adaptions in the lipid metabolism. Since sCD163 is shed to serum by inflammatory signals including lipopolysaccharides (LPS, endotoxin, we investigated sCD163 and correlations with lipid metabolism following LPS exposure. Methods: Eight healthy male subjects were investigated on two separate occasions: (i following an LPS exposure and (ii following saline exposure. Each study day consisted of a four-hour non-insulin-stimulated period followed by a two-hour hyperinsulinemic euglycemic clamp period. A 3H-palmitate tracer was used to calculate the rate of appearance (Rapalmitate. Blood samples were consecutively obtained throughout each study day. Abdominal subcutaneous adipose tissue was obtained for western blotting. Results: We observed a significant two-fold increase in plasma sCD163 levels following LPS exposure (P < 0.001, and sCD163 concentrations correlated positively with the plasma concentration of free fatty acids, Rapalmitate, lipid oxidation rates and phosphorylation of the hormone-sensitive lipase at serine 660 in adipose tissue (P < 0.05, all. Furthermore, sCD163 concentrations correlated positively with plasma concentrations of cortisol, glucagon, tumour necrosis factor (TNF-α, interleukin (IL-6 and IL-10 (P < 0.05, all. Conclusion: We observed a strong correlation between sCD163 and stimulation of lipolysis and fat oxidation following LPS exposure. These findings support preexisting theory that inflammation and macrophage activation play a significant role in lipid metabolic adaptions under conditions such as obesity, DM2 and NAFLD.

  13. Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.

    Science.gov (United States)

    Craig, D G; Lee, P; Pryde, E A; Hayes, P C; Simpson, K J

    2013-12-01

    Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose. © 2013 John Wiley & Sons Ltd.

  14. Generation of a haptoglobin-hemoglobin complex-specific Fab antibody blocking the binding of the complex to CD163

    DEFF Research Database (Denmark)

    Horn, Ivo R; Nielsen, Marianne Jensby; Madsen, Mette

    2003-01-01

    During intravascular hemolysis hemoglobin (Hb) binds to haptoglobin (Hp) leading to endocytosis of the complex by the macrophage receptor, CD163. In the present study, we used a phage-display Fab antibody strategy to explore if the complex formation between Hp and Hb leads to exposure of antigenic...... epitopes specific for the complex. By Hp-Hb-affinity screening of a phage-Fab library, we isolated a phage clone against the ligand complex. Surface plasmon resonance analyses of the Fab part expressed as a recombinant protein revealed a high affinity binding (KD = 3.9 nm) to Hp-Hb, whereas no binding...... was measured for non-complexed Hp or Hb. The Fab antibody completely inhibited the binding of 125I-labeled Hp-Hb complexes to CD163 and blocked their uptake in CD163-transfected cells. In conclusion, we have raised a receptor-blocking antibody specifically recognizing the Hp-Hb complex. In addition to provide...

  15. Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin

    DEFF Research Database (Denmark)

    Kronborg, Camilla S; Knudsen, Ulla Breth; Moestrup, Søren K

    2007-01-01

    BACKGROUND: Alternatively activated macrophages expressing the CD163 and CD206 surface receptors are the dominant immune-cell type found in the placenta. The placental number and distribution of macrophages is altered in pre-eclampsia, and the generalised inflammatory reaction associated with pre-eclampsia...... might lead to shedding of soluble CD163 into the circulation. METHODS: Serum samples from 18 women with pre-eclampsia and 90 normal pregnancies were obtained from a longitudinal study of 955 pregnant women at Randers County Hospital, Denmark. sCD163 and Neopterin were measured by ELISA on samples....... Neopterin increased throughout pregnancy in both healthy (from median 5.4 to 6.7 nmol/l, ppre-eclampsia...

  16. Visceral obesity is associated with increased soluble CD163 concentration in men with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Sørensen, Lars Peter; Parkner, Tina; Søndergaard, Esben

    2015-01-01

    individuals. The objective was to examine the effect of male overweight/obesity and type 2 diabetes mellitus (T2DM) on associations between adiposity parameters and sCD163. A total of 23 overweight/obese non-diabetic men, 16 overweight/obese men with T2DM, and a control group of 20 normal-weight healthy men...... multiple linear regression analysis. In the normal-weight healthy men, there was no significant association between adiposity parameters and sCD163, whereas in the overweight/obese non-diabetic men, measures of general and regional adiposity were positively associated with sCD163. In the overweight/obese......-body fat, adjusted for BMI and age, VAT remained a significant predictor of sCD163 in the overweight/obese T2DM men, but not in the overweight/obese non-diabetic men. Our results indicate that VAT inflammation is exaggerated in men with T2DM, and that propensity to store excess body fat viscerally...

  17. Soluble hemoglobin-haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndrome

    DEFF Research Database (Denmark)

    Schaer, Dominik J; Schleiffenbaum, Boris; Kurrer, Michael

    2005-01-01

    .1 mg/L), acute mononucleosis (median 8.2 mg/L), Leishmania infection (median 6.7 mg/L) and healthy controls (median 1.8 mg/L). Follow-up of patients with a relapsing course of the disease revealed close correlations of sCD163 with clinical disease activity, serum ferritin and other markers...

  18. Distribution of CD163-positive cell and MHC class II-positive cell in the normal equine uveal tract.

    Science.gov (United States)

    Sano, Yuto; Matsuda, Kazuya; Okamoto, Minoru; Takehana, Kazushige; Hirayama, Kazuko; Taniyama, Hiroyuki

    2016-02-01

    Antigen-presenting cells (APCs) in the uveal tract participate in ocular immunity including immune homeostasis and the pathogenesis of uveitis. In horses, although uveitis is the most common ocular disorder, little is known about ocular immunity, such as the distribution of APCs. In this study, we investigated the distribution of CD163-positive and MHC II-positive cells in the normal equine uveal tract using an immunofluorescence technique. Eleven eyes from 10 Thoroughbred horses aged 1 to 24 years old were used. Indirect immunofluorescence was performed using the primary antibodies CD163, MHC class II (MHC II) and CD20. To demonstrate the site of their greatest distribution, positive cells were manually counted in 3 different parts of the uveal tract (ciliary body, iris and choroid), and their average number was assessed by statistical analysis. The distribution of pleomorphic CD163- and MHC II-expressed cells was detected throughout the equine uveal tract, but no CD20-expressed cells were detected. The statistical analysis demonstrated the distribution of CD163- and MHC II-positive cells focusing on the ciliary body. These results demonstrated that the ciliary body is the largest site of their distribution in the normal equine uveal tract, and the ciliary body is considered to play important roles in uveal and/or ocular immune homeostasis. The data provided in this study will help further understanding of equine ocular immunity in the normal state and might be beneficial for understanding of mechanisms of ocular disorders, such as equine uveitis.

  19. CD163+ Tumor-Associated Macrophages Correlated with Poor Prognosis and Cancer Stem Cells in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ke-Fei He

    2014-01-01

    Full Text Available Tumor-associated macrophages (TAMs play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P<0.05. Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P<0.05. TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.

  20. Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment

    International Nuclear Information System (INIS)

    Mori, Kazumasa; Haraguchi, Shigeki; Hiori, Miki; Shimada, Jun; Ohmori, Yoshihiro

    2015-01-01

    Tumor-associated macrophages (TAMs) are implicated in the growth, invasion and metastasis of various solid tumors. However, the phenotype of TAMs in premalignant lesions of solid tumors has not been clarified. In the present study, we identify the phenotype of TAMs in leukoplakia, an oral premalignant lesion, by immunohistochemical analysis and investigate the involvement of infiltrated T cells that participate in the polarization of TAMs. The subjects included 30 patients with oral leukoplakia and 10 individuals with normal mucosa. Hematoxylin and eosin slides were examined for the histological grades, and immunohistochemical analysis was carried out using antibodies against CD68 (pan-MΦ), CD80 (M1 MΦ), CD163 (M2 MΦ), CD4 (helper T cells: Th), CD8 (cytotoxic T cells), CXCR3, CCR5 (Th1), CCR4 (Th2), signal transducer and activator of transcription (STAT1), phosphorylated STAT1 (pSTAT1) and chemokine CXCL9. The differences in the numbers of positively stained cells among the different histological grades were tested for statistical significance using the Kruskal-Wallis test. Correlations between different types of immune cells were determined using Spearman’s rank analysis. An increase in the rate of CD163 + TAM infiltration was observed in mild and moderate epithelial dysplasia, which positively correlated with the rate of intraepithelial CD4 + Th cell infiltration. Although CCR4 + cells rarely infiltrated, CXCR3 + and CCR5 + cells were observed in these lesions. Cells positive for STAT1 and chemokine CXCL9, interferon- (IFN)-induced gene products, and pSTAT1 were also observed in the same lesions. Double immunofluorescence staining demonstrated that the cells that were positive for CD163 were also positive for STAT1. CD163 + TAMs in oral premalignant lesions coexpress CD163 and STAT1, suggesting that the TAMs in oral premalignant lesions possess an M1 phenotype in a Th1-dominated micromilieu

  1. CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.

    Science.gov (United States)

    Rubio-Navarro, Alfonso; Carril, Mónica; Padro, Daniel; Guerrero-Hue, Melanie; Tarín, Carlos; Samaniego, Rafael; Cannata, Pablo; Cano, Ainhoa; Villalobos, Juan Manuel Amaro; Sevillano, Ángel Manuel; Yuste, Claudia; Gutiérrez, Eduardo; Praga, Manuel; Egido, Jesús; Moreno, Juan Antonio

    2016-01-01

    Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.

  2. Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis

    DEFF Research Database (Denmark)

    Grønbæk, Henning; Kazankov, Konstantin; Jessen, Niels

    Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis......Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis...

  3. Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

    DEFF Research Database (Denmark)

    Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

    2004-01-01

    CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin complexes. The extracellular region consisting of nine scavenger receptor cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By ligand binding analysis of a broad spectrum of soluble CD163...... truncation variants, the amino-terminal third of the SRCR region was shown to be crucial for the binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163 variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3, 4, 6, 7, and 9, respectively. Only the two antibodies...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...

  4. Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions.

    Science.gov (United States)

    Alvarado-Vazquez, Perla Abigail; Bernal, Laura; Paige, Candler A; Grosick, Rachel L; Moracho Vilrriales, Carolina; Ferreira, David Wilson; Ulecia-Morón, Cristina; Romero-Sandoval, E Alfonso

    2017-08-01

    M1 macrophages release proinflammatory factors during inflammation. They transit to an M2 phenotype and release anti-inflammatory factors to resolve inflammation. An imbalance in the transition from M1 to M2 phenotype in macrophages contributes to the development of persistent inflammation. CD163, a member of the scavenger receptor cysteine-rich family, is an M2 macrophage marker. The functional role of CD163 during the resolution of inflammation is not completely known. We postulate that CD163 contributes to the transition from M1 to M2 phenotype in macrophages. We induced CD163 gene in THP-1 and primary human macrophages using polyethylenimine nanoparticles grafted with a mannose ligand (Man-PEI). This nanoparticle specifically targets cells of monocytic origin via mannose receptors. Cells were challenged with a single or a double stimulation of lipopolysaccharide (LPS). A CD163 or empty plasmid was complexed with Man-PEI nanoparticles for cell transfections. Quantitative RT-PCR, immunocytochemistry, and ELISAs were used for molecular assessments. CD163-overexpressing macrophages displayed reduced levels of tumor necrosis factor-alpha (TNF)-α and monocytes chemoattractant protein (MCP)-1 after a single stimulation with LPS. Following a double stimulation paradigm, CD163-overexpressing macrophages showed an increase of interleukin (IL)-10 and IL-1ra and a reduction of MCP-1. This anti-inflammatory phenotype was partially blocked by an anti-CD163 antibody (effects on IL-10 and IL-1ra). A decrease in the release of TNF-α, IL-1β, and IL-6 was observed in CD163-overexpressing human primary macrophages. The release of IL-6 was blocked by an anti-CD163 antibody in the CD163-overexpressing group. Our data show that the induction of the CD163 gene in human macrophages under inflammatory conditions produces changes in cytokine secretion in favor of an anti-inflammatory phenotype. Targeting macrophages to induce CD163 using cell-directed nanotechnology is an attractive

  5. Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis

    DEFF Research Database (Denmark)

    Grønbaek, H; Sandahl, T D; Mortensen, C

    2012-01-01

    BACKGROUND: Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells. AIM: To study soluble plasma (s) CD163, a specific marker of activated macrophages......, as a biomarker for portal hypertension in patients with liver cirrhosis. METHODS: We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured...... for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention....

  6. Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients

    DEFF Research Database (Denmark)

    Knudsen, T.B.; Gustafson, P.; Kronborg, G.

    2005-01-01

    Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verif......Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among...

  7. Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin

    DEFF Research Database (Denmark)

    Knudsen, Troels Bygum; Larsen, Klaus; Kristiansen, Thomas Birk

    2007-01-01

    The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected of meningi......The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected...... marker for distinguishing bacterial infection from non-bacterial disease (specificity 0.91; sensitivity 0.47). However, the overall diagnostic accuracy of CRP (AUC =0.91) and PCT (AUC =0.87) were superior (p... infection, the AUC of sCD163 (0.83) did not differ significantly from those of CRP or PCT. All markers had AUCs CRP and PCT had high diagnostic value and were superior as markers of bacterial infection compared to s...

  8. Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

    DEFF Research Database (Denmark)

    Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

    2004-01-01

    binding to SRCR domain 3 exhibited effective inhibition of ligand binding. Furthermore, analysis of purified native CD163 revealed that proteolytic cleavage in SRCR domain 3 inactivates ligand binding. Calcium protects against cleavage in this domain. Analysis of the calcium sensitivity of ligand binding...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...... for the calcium-sensitive coupling of haptoglobin.hemoglobin complexes....

  9. The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis

    DEFF Research Database (Denmark)

    Sandahl, T D; McGrail, R; Møller, H J

    2016-01-01

    BACKGROUND: Noninvasive identification of significant portal hypertension in patients with cirrhosis is needed in hepatology practice. AIM: To investigate whether the combination of sCD163 as a hepatic inflammation marker and the fibrosis markers of the Enhanced Liver Fibrosis score (ELF) can...... predict portal hypertension in patients with cirrhosis. METHODS: We measured sCD163 and the ELF components (hyaluronic acid, tissue inhibitor of metalloproteinase-1 and procollagen-III aminopeptide) in two separate cohorts of cirrhosis patients that underwent hepatic vein catheterisation. To test...... the predictive accuracy we developed a CD163-fibrosis portal hypertension score in an estimation cohort (n = 80) and validated the score in an independent cohort (n = 80). A HVPG ≥10 mmHg was considered clinically significant. RESULTS: Both sCD163 and the ELF components increased in a stepwise manner...

  10. Neutrophil and Monocyte CD64 and CD163 Expression in Critically Ill Neonates and Children with Sepsis: Comparison of Fluorescence Intensities and Calculated Indexes

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    Mojca Groselj-Grenc

    2008-01-01

    Full Text Available Objective. To evaluate the expression of CD64 and CD163 on neutrophils and monocytes in SIRS with/without sepsis and to compare the diagnostic accuracy of CD64 and CD163 molecules expression determined as (1 mean fluorescence intensities (MFI of CD64 and CD163; and (2 the ratio (index of linearized MFI to the fluorescence signal of standardized beads. Patients and methods. Fifty-six critically ill neonates and children with systemic inflammatory response syndrome (SIRS and suspected sepsis, classified into two groups: SIRS with sepsis (n=29 and SIRS without sepsis (n=27. Results. CD64 and CD163 MFI measured on neutrophils and monocytes were elevated in patients with SIRS with sepsis. Diagnostic accuracy of indexes was equal to diagnostic accuracy of MFI for CD64 on neutrophils (0.833 versus 0.854 for day 0 and 0.975 versus 0.983 for day 1 and monocytes (0.811 versus 0.865 for day 0 and 0.825 versus 0.858 for day 1, and CD163 on neutrophils (0.595 versus 0.655 for day 0 and 0.677 versus 0.750 for day 1, but not for CD163 on monocytes. Conclusion. CD64 MFI, CD163 MFI, CD64 indexes for neutrophils and monocytes, and CD163 index for neutrophils can all be used for discrimination of SIRS and sepsis in critically ill neonates and children. CD64 index for neutrophils, however, is superior to all other markers.

  11. Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery.

    Science.gov (United States)

    Garvin, Stina; Oda, Husam; Arnesson, Lars-Gunnar; Lindström, Annelie; Shabo, Ivan

    2018-05-03

    Cancer cell fusion with macrophages results in highly tumorigenic hybrids that acquire genetic and phenotypic characteristics from both maternal cells. Macrophage traits, exemplified by CD163 expression, in tumor cells are associated with advanced stages and poor prognosis in breast cancer (BC). In vitro data suggest that cancer cells expressing CD163 acquire radioresistance. Tissue microarray was constructed from primary BC obtained from 83 patients treated with breast-conserving surgery, 50% having received postoperative radiotherapy (RT) and none of the patients had lymph node or distant metastasis. Immunostaining of CD163 in cancer cells and macrophage infiltration (MI) in tumor stroma were evaluated. Macrophage:MCF-7 hybrids were generated by spontaneous in vitro cell fusion. After irradiation (0, 2.5 and 5 Gy γ-radiation), both hybrids and their maternal MCF-7 cells were examined by clonogenic survival. CD163-expression by cancer cells was significantly associated with MI and clinicopathological data. Patients with CD163-positive tumors had significantly shorter disease-free survival (DFS) after RT. In vitro generated macrophage:MCF-7 hybrids developed radioresistance and exhibited better survival and colony forming ability after radiation compared to maternal MCF-7 cancer cells. Our results suggest that macrophage phenotype in tumor cells results in radioresistance in breast cancer and shorter DFS after radiotherapy.

  12. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function

    DEFF Research Database (Denmark)

    Kallestrup, M; Møller, Holger Jon; Tankisi, H

    2015-01-01

    and serum in participants with neuropathy than in those without neuropathy [cerebrospinal fluid: median (range) 131 (86-173) vs 101 (70-190) μg/l, P = 0.08 and serum: 3725 (920-7060) vs 2220 (1130-4780), P = 0.06). CONCLUSIONS: Cerebrospinal fluid soluble CD163 level is associated with impaired peripheral......AIMS: To measure soluble CD163 levels in the cerebrospinal fluid and serum of people with Type 2 diabetes, with and without polyneuropathy, and to relate the findings to peripheral nerve function. METHODS: A total of 22 people with Type 2 diabetes and 12 control subjects without diabetes were...... included in this case-control study. Participants with diabetes were divided into those with neuropathy (n = 8) and those without neuropathy (n = 14) based on clinical examination, vibratory perception thresholds and nerve conduction studies. Serum and cerebrospinal fluid soluble CD163 levels were analysed...

  13. Prognostic significance of interleukin-8 and CD163-positive cell-infiltration in tumor tissues in patients with oral squamous cell carcinoma.

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    Yohei Fujita

    Full Text Available PURPOSE: We investigated whether serum interleukin (IL-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC. EXPERIMENTAL DESIGN: Fifty OSCC patients who received radical resection of their tumor(s were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens. RESULTS: We found that disease-free survival (DFS was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001. The tumor expression of IL-8, i.e., IL-8(T and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively, and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS in all patients. A multivariate analysis revealed that N status, IL-8(T and CD163(IF significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T or CD163(IF may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10. CONCLUSIONS: These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.

  14. Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model

    DEFF Research Database (Denmark)

    Tentillier, Noemie; Etzerodt, Anders; Olesen, Mads N

    2016-01-01

    intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia...

  15. Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

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    Alison Castley

    Full Text Available We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p0.2. Associations between higher sCD163 and protease inhibitor therapy (p = 0.05 and lower sCD14 with integrase inhibitor therapy (p = 0.02 were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI, with a favourable influence of Framingham score <10% (p = 0.04. Soluble CD14 levels were higher among smokers (p = 0.002, with no effect of other CVD risk factors, except age (p = 0.045. Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation.

  16. Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors

    Science.gov (United States)

    Castley, Alison; Williams, Leah; James, Ian; Guelfi, George; Berry, Cassandra; Nolan, David

    2016-01-01

    We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation. PMID:27355513

  17. Biodistribution and PET Imaging of a Novel [(68)Ga]-Anti-CD163-Antibody Conjugate in Rats with Collagen-Induced Arthritis and in Controls

    DEFF Research Database (Denmark)

    Eichendorff, Sascha; Svendsen, Pia; Bender, Dirk

    2015-01-01

    -68 and evaluated stability and binding specificity of the conjugate ([(68)Ga]ED2) in vitro. Furthermore, tracer biodistribution was assessed in vivo in healthy rats and rats with acute collagen-induced arthritis (CIA) by MicroPET and tissue analysis. RESULTS: Radiosynthesis of [(68)Ga]ED2 antibody...... was also changed in the sense that a significantly higher liver uptake and lower spleen uptake of [(68)Ga]ED2 was measured in CIA rats that accordingly showed a corresponding change in level of CD163 expression. CONCLUSIONS: [(68)Ga]ED2 specifically binds CD163 in vitro and in vivo. Biodistribution studies...... in CIA rats suggest that this novel tool may have applications in studies of inflammatory diseases....

  18. Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Deichgræber, Pia; Witte, Daniel R; Møller, Holger J

    2016-01-01

    -up examination (ADDITION-Progression [ADDITION-PRO]) in 2009–2011. Baseline serum samples were analysed for sCD163, adiponectin and CRP. The associations between sCD163, adiponectin and CRP per doubling of concentration, and changes per year in HbA1c, fasting plasma glucose, 2 h glucose, fasting insulin, HOMA-IR....... A doubling of adiponectin was inversely associated with changes in 2 h glucose (β =−0.063 per year, 95% CI −0.111, −0.014), HOMA-IR (β =−0.038 per year, 95% CI −0.060, −0.015) and HOMA-β (β =−1.028 per year, 95% CI −1.635, −0.421) after adjustment for age and sex. The associations were robust to adjustment...... and HOMA-β were assessed using a mixed-effects model. Results: A doubling of sCD163 concentration was positively associated with changes in HOMA-β (β = 1.160 per year, 95% CI 0.345, 1.975) as well as a doubling of CRP concentration (β = 0.410 per year, 95% CI 0.051, 0.769) after adjustment for age and sex...

  19. Serum levels of TWEAK and scavenger receptor CD163 in type 1 diabetes mellitus: relationship with cardiovascular risk factors. a case-control study.

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    Gemma Llauradó

    Full Text Available OBJECTIVE: To test the usefulness of serum concentrations of tumor necrosis factor-like weak inducer of apoptosis (sTWEAK and soluble scavenger receptor CD163 (sCD163 as markers of subtle inflammation in patients with type 1 diabetes mellitus (T1DM without clinical cardiovascular (CV disease and to evaluate their relationship with arterial stiffness (AS. METHODS: Sixty-eight patients with T1DM and 68 age and sex-matched, healthy subjects were evaluated. Anthropometrical variables and CV risk factors were recorded. Serum concentrations of sTWEAK and sCD163 were measured. AS was assessed by aortic pulse wave velocity (aPWV. All statistical analyses were stratified by gender. RESULTS: T1DM patients showed lower serum concentrations of sTWEAK (Men: 1636.5 (1146.3-3754.8 pg/mL vs. 765.9 (650.4-1097.1 pg/mL; p<0.001. Women: 1401.0 (788.0-2422.2 pg/mL vs. 830.1 (562.6-1175.9 pg/mL; p = 0.011 compared with their respective controls. Additionally, T1DM men had higher serum concentrations of sCD163 (285.0 (247.7-357.1 ng/mL vs. 224.8 (193.3-296.5 ng/mL; p = 0.012 compared with their respective controls. sTWEAK correlated negatively with aPWV in men (r = -0.443; p<0.001. However, this association disappeared after adjusting for potential confounders. In men, the best multiple linear regression model showed that the independent predictors of sTWEAK were T1DM and WHR (R(2 = 0.640; p<0.001. In women, T1DM and SBP were the independent predictors for sTWEAK (R(2 = 0.231; p = 0.001. CONCLUSION: sTWEAK is decreased in T1DM patients compared with age and sex-matched healthy subjects after adjusting for classic CV risk factors, although sTWEAK levels may be partially influenced by some of them. Additionally, T1DM men have higher serum concentrations of sCD163. These results point out an association between the inflammatory system and CV risk in T1DM.

  20. Changes in fat mass correlate with changes in soluble sCD163, a marker of mature macrophages, in patients with CKD

    DEFF Research Database (Denmark)

    Axelsson, Jonas; Møller, Holger Jon; Witasp, Anna

    2006-01-01

    healthy controls (mean GFR, 89 +/- 3 mL/min [1.48 +/- 0.05 mL/s]; mean age, 63 +/-2 years; 69% men) were characterized post hoc with a follow-up of up to 5 years (mean, 47 +/- 1 months). sCD163 levels, body composition (dual-energy x-ray absorptiometry), clinical parameters, and levels of circulating...... of inflammation and endothelial adhesion molecules. After 1 year, patients who increased body fat mass (average, 11% +/- 5% versus -5% +/- 5%; P

  1. Elevated Plasma Soluble CD14 and Skewed CD16+ Monocyte Distribution Persist despite Normalisation of Soluble CD163 and CXCL10 by Effective HIV Therapy: A Changing Paradigm for Routine HIV Laboratory Monitoring?

    Science.gov (United States)

    Castley, Alison; Berry, Cassandra; French, Martyn; Fernandez, Sonia; Krueger, Romano; Nolan, David

    2014-01-01

    Objective We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice. Design Cross-sectional evaluation of concurrent plasma and whole blood samples. Methods A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14), soluble CD163 (sCD163) and CXCL10 were measured by ELISA. Results HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001). Conclusions Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune activation in HIV

  2. Elevated plasma soluble CD14 and skewed CD16+ monocyte distribution persist despite normalisation of soluble CD163 and CXCL10 by effective HIV therapy: a changing paradigm for routine HIV laboratory monitoring?

    Directory of Open Access Journals (Sweden)

    Alison Castley

    Full Text Available OBJECTIVE: We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice. DESIGN: Cross-sectional evaluation of concurrent plasma and whole blood samples. METHODS: A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14, soluble CD163 (sCD163 and CXCL10 were measured by ELISA. RESULTS: HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001. CONCLUSIONS: Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune

  3. A possible mechanism in the recruitment of eosinophils and Th2 cells through CD163(+) M2 macrophages in the lesional skin of eosinophilic cellulitis.

    Science.gov (United States)

    Fujimura, Taku; Kambayashi, Yumi; Furudate, Sadanori; Kakizaki, Aya; Aiba, Setsuya

    2014-01-01

    M2 macrophages play a critical role in the recruitment of T helper 2 (Th2) regulatory T cells (Treg). To study the role of M2 macrophages and Treg cells in eosinophilic celulitis. We employed immunohistochemical staining for CD163( )and CD206 (macrophages) as well as FoxP3 (Treg), in lesional skin of four cases of eosinophilic cellulitis. CD163(+) CD206(+) M2 macrophages, which were previously reported to produce CCL17 to induce Th2 cells and Treg cells, were predominantly infiltrating the subcutaneous tissues and interstitial area of the dermis. M2 macrophages derived from PBMC showed significantly increased expression of CCL11, CCL17, CCL24 and CCL26 mRNA and production of CCL17 and CCL24, when stimulated by IL-4 or IL- 13. In addition, CCL17-producing cells and CCL24-producing cells were prominent in the lesional skin of EC. Our study sheds light on one of the possible immunological mechanisms of eosinophilic cellulitis.

  4. A macrophage activation switch (MAcS)-index for assessment of monocyte/macrophage activation

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Lauridsen, Mette; Knudsen, Troels Bygum

    2008-01-01

    , simplified by the M1-M2 dichotomy of classically activated (M1), pro-inflammatory cells and alternatively activated (M2), anti-inflammatory cells. Macrophages, however, display a large degree of flexibility and are able to switch between activation states (1). The hemoglobin scavenger receptor CD163...... is expressed exclusively on monocytes and macrophages, and its expression is strongly induced by anti-inflammatory stimuli like IL10 and glucocorticoid, making CD163 an ideal M2 macrophage marker (2). Furthermore a soluble variant of CD163 (sCD163) is shed from the cell surface to plasma by protease mediated.......058-5139) (panti-inflammatory state.   CONCLUSION: We present a CD163-derived macrophage activation switch (MAcS)-index, which seems able to differentiate between (predominantly) pro-inflammatory and anti-inflammatory macrophage activation. The index needs...

  5. The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

    Directory of Open Access Journals (Sweden)

    Chandra M Ohri

    Full Text Available BACKGROUND: We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM expression of proteins associated with M1 and M2 macrophages in NSCLC. METHODS: Using immunohistochemistry, CD68(+ macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14, or a non-cytotoxic M2 phenotype (CD163 and VEGF were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES (median 92.7 months and 20 patients with poor survival (PS (median 7.7 months. RESULTS: The NM expression of NM-HLA-DR (p<0.001, NM-iNOS (p = 0.02 and NM-MRP 8/14 (p = 0.02 was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (p<0.001. There was more NM-CD163 expression (p = 0.04 but less NM-iNOS (p = 0.002 and MRP 8/14 (p = 0.01 expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR p<0.001, 65.0% versus 14.6% (NM-iNOS p = 0.003, and 54.3% versus 22.2% (NM-MRP 8/14 p = 0.04, as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41 and 19.4% versus 59.0% (NM-VEGF p = 0.001. CONCLUSIONS: Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

  6. Investigation of human cationic antimicrobial protein-18 (hCAP-18), lactoferrin and CD163 as potential biomarkers for ovarian cancer

    DEFF Research Database (Denmark)

    Lim, Ratana; Lappas, Martha; Riley, Clyde

    2013-01-01

    controls, including 28 women with benign pelvic masses; 91 cancer, including 21 women with borderline tumours). Localisation of each antigen within the ovary was assessed by immunohistochemistry and serum concentrations determined by ELISA assays. RESULTS: Immunoreactive (ir) hCAP-18 and lactoferrin were......BACKGROUND: Epithelial ovarian cancer is one of the leading causes of gynaecological cancer morbidity and mortality in women. Early stage ovarian cancer is usually asymptomatic, therefore, is often first diagnosed when it is widely disseminated. Currently available diagnostics lack the requisite...... and plasma concentrations of three putative ovarian cancer biomarkers: human cationic antimicrobial protein-18 (hCAP-18); lactoferrin; and CD163 in normal healthy women and women with ovarian cancer. METHODS: In this case-control cohort study, ovarian tissue and blood samples were obtained from 164 women (73...

  7. The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC.

    Science.gov (United States)

    Ohri, Chandra M; Shikotra, Aarti; Green, Ruth H; Waller, David A; Bradding, Peter

    2011-01-01

    We have previously investigated the microlocalisation of M1 and M2 macrophages in NSCLC. This study investigated the non-macrophage (NM) expression of proteins associated with M1 and M2 macrophages in NSCLC. Using immunohistochemistry, CD68(+) macrophages and proteins associated with either a cytotoxic M1 phenotype (HLA-DR, iNOS, and MRP 8/14), or a non-cytotoxic M2 phenotype (CD163 and VEGF) were identified. NM expression of the markers was analysed in the islets and stroma of surgically resected tumours from 20 patients with extended survival (ES) (median 92.7 months) and 20 patients with poor survival (PS) (median 7.7 months). The NM expression of NM-HLA-DR (pMRP 8/14 (p = 0.02) was increased in ES compared to PS patients in the tumour islets. The tumour islet expression of NM-VEGF, was decreased in ES compared to PS patients (pMRP 8/14 (p = 0.01) expression in the stroma of ES patients compared with PS patients. The 5-year survival for patients with above and below median NM expression of the markers in the islets was 74.9% versus 4.7% (NM-HLA-DR pMRP 8/14 p = 0.04), as opposed to 34.1% versus 44.4% (NM-CD163 p = 0.41) and 19.4% versus 59.0% (NM-VEGF p = 0.001). Cell proteins associated with M1 and M2 macrophages are also expressed by other cell types in the tumour islets and stroma of patients with NSCLC. Their tissue and cellular microlocalisation is associated with important differences in clinical outcome.

  8. Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function.

    Directory of Open Access Journals (Sweden)

    Christine Burkard

    2017-02-01

    Full Text Available Porcine Reproductive and Respiratory Syndrome (PRRS is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV. PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5 region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs and peripheral blood monocytes (PBMCs were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages.

  9. Simian Hemorrhagic Fever Virus Cell Entry Is Dependent on CD163 and Uses a Clathrin-Mediated Endocytosis-Like Pathway

    OpenAIRE

    Caì, Yíngyún; Postnikova, Elena N.; Bernbaum, John G.; Yú, Shuǐqìng; Mazur, Steven; Deiuliis, Nicole M.; Radoshitzky, Sheli R.; Lackemeyer, Matthew G.; McCluskey, Adam; Robinson, Phillip J.; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L.; Lauck, Michael; Friedrich, Thomas C.

    2014-01-01

    Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A ...

  10. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    Energy Technology Data Exchange (ETDEWEB)

    Du, Yijun [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan (China); Pattnaik, Asit K. [School of Veterinary Medicine and Biomedical Sciences and the Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583-0900 (United States); Song, Cheng [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Yoo, Dongwan, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Li, Gang, E-mail: dyoo@illinois.edu [Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 South Lincoln Ave, Urbana, IL 61802 (United States); Institute of Animal Science and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Beijing (China)

    2012-03-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 ({omega} - 2, where {omega} is the GPI moiety at E160), P159 ({omega} - 1), and M162 ({omega} + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide-anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  11. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts

    International Nuclear Information System (INIS)

    Du, Yijun; Pattnaik, Asit K.; Song, Cheng; Yoo, Dongwan; Li, Gang

    2012-01-01

    The porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 4 (GP4) resembles a typical type I membrane protein in its structure but lacks a hydrophilic tail at the C-terminus, suggesting that GP4 may be a lipid-anchored membrane protein. Using the human decay-accelerating factor (DAF; CD55), a known glycosyl-phosphatidylinositol (GPI) lipid-anchored protein, chimeric constructs were made to substitute the GPI-anchor domain of DAF with the putative lipid-anchor domain of GP4, and their membrane association and lipase cleavage were determined in cells. The DAF-GP4 fusion protein was transported to the plasma membrane and was cleaved by phosphatidylinositol-specific phospholipase C (PI-PLC), indicating that the C-terminal domain of GP4 functions as a GPI anchor. Mutational studies for residues adjacent to the GPI modification site and characterization of respective mutant viruses generated from infectious cDNA clones show that the ability of GP4 for membrane association corresponded to virus viability and growth characteristics. The residues T158 (ω − 2, where ω is the GPI moiety at E160), P159 (ω − 1), and M162 (ω + 2) of GP4 were determined to be important for virus replication, with M162 being of particular importance for virus infectivity. The complete removal of the peptide–anchor domain in GP4 resulted in a complete loss of virus infectivity. The depletion of cholesterol from the plasma membrane of cells reduced the virus production, suggesting a role of lipid rafts in PRRSV infection. Remarkably, GP4 was found to co-localize with CD163 in the lipid rafts on the plasma membrane. Since CD163 has been reported as a cellular receptor for PRRSV and GP4 has been shown to interact with this receptor, our data implicates an important role of lipid rafts during entry of the virus.

  12. 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...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... 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...

  13. The Staphylococcus aureus Protein IsdH Inhibits Host Hemoglobin Scavenging to Promote Heme Acquisition by the Pathogen

    DEFF Research Database (Denmark)

    Saederup, Kirstine Lindhardt; Stødkilde-Jørgensen, Kristian; Graversen, Jonas Heilskov

    2016-01-01

    Hemolysis is a complication in septic infections with Staphylococcus aureus, which utilizes the released Hb as an iron source. S. aureus can acquire heme in vitro from hemoglobin (Hb) by a heme-sequestering mechanism that involves proteins from the S. aureus iron-regulated surface determinant (Isd...

  14. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Madsen, Mette; Moestrup, Søren K

    2002-01-01

    as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp). This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular...

  15. Early Erythrolysis in the Hematoma After Experimental Intracerebral Hemorrhage

    Science.gov (United States)

    Dang, Ge; Yang, Yuefan; Wu, Gang; Hua, Ya; Keep, Richard F.; Xi, Guohua

    2016-01-01

    Erythrolysis occurs in the clot after intracerebral hemorrhage (ICH) and the release of hemoglobin causes brain injury but it is unclear when such lysis occurs. The present study examined early erythrolysis in rats. ICH rats had an intra-caudate injection of 100 µl autologous blood and sham rats had a needle insertion. All rats had T2 and T2* MRI scanning and brains were used for histology and CD163 (a hemoglobin scavenger receptor) and DARPP-32 (a neuronal marker) immunohistochemistry. There was marked heterogeneity within the hematoma on T2* MRI, with a hyper- or isointense core and a hypointense periphery. Hematoxylin and eosin staining in the same animals showed significant erythrolysis in the core with the formation of erythrocyte ghosts. The degree of erythrolysis correlated with the severity of perihematomal neuronal loss. Perihematomal CD163 was increased by day 1 after ICH and may be involved in clearing hemoglobin caused by early hemolysis. Furthermore, ICH resulted in more severe erythrolysis, neuronal loss and perihematomal CD163 upregulation in spontaneously hypertensive rats compared to Wistar Kyoto rats. In conclusions, T2*MRI detectable early erythrolysis occurred in the clot after ICH, and activated CD163. Hypertension is associated with enhanced erythrolysis in the hematoma. PMID:27783383

  16. Anti-CD163-dexamethasone protects against apoptosis after ischemia/reperfusion injuries in the rat liver

    DEFF Research Database (Denmark)

    Møller, Lin Nanna Okholm; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt

    2015-01-01

    , high dose dexamethasone, low dose dexamethasone or placebo intravenously 18 h before laparotomy with subsequent 60 min of liver ischemia. After reperfusion for 24 h the animals had their liver removed. Bloods were drawn 30 min and 24 h post ischemia induction. Liver cell apoptosis and necrosis were...

  17. Soluble macrophage-derived CD163: a homogenous ectodomain protein with a dissociable haptoglobin-hemoglobin binding

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Nielsen, Marianne Jensby; Maniecki, Maciej Bogdan

    2010-01-01

    species in serum (from 50 healthy subjects and 29 patients) were measured with domain-specific ELISAs, purified from serum (from 6 individuals) by affinity chromatography and identified by western blotting and MALDI-TOF/TOF mass spectrometry. Binding to Hp-Hb complexes was investigated by gel...

  18. Antibody-Directed Glucocorticoid Targeting to CD163 in M2-type Macrophages Attenuates Fructose-Induced Liver Inflammatory Changes

    DEFF Research Database (Denmark)

    Svendsen, Pia; Graversen, Jonas Heilskov; Etzerodt, Anders

    2017-01-01

    Increased consumption of high-caloric carbohydrates contributes substantially to endemic non-alcoholic fatty liver disease in humans, covering a histological spectrum from fatty liver to steatohepatitis. Hypercaloric intake and lipogenetic effects of fructose and endotoxin-driven activation...... changes in rats on a high-fructose diet. The diet induced severe non-alcoholic steatohepatitis (NASH)-like changes within a few weeks but the antibody-drug conjugate strongly reduced inflammation, hepatocyte ballooning, fibrosis, and glycogen deposition. Non-conjugated dexamethasone or dexamethasone...... seems to be a promising approach for safe treatment of fructose-induced liver inflammation....

  19. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  20. CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3

    Directory of Open Access Journals (Sweden)

    Lucía Sanjurjo

    2018-03-01

    Full Text Available CD5L (CD5 molecule-like is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization.

  1. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  2. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  3. 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....

  4. 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....

  5. 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....

  6. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    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 su...

  7. Micro dynamics in mediation

    OpenAIRE

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  8. Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus.

    Science.gov (United States)

    Hogan, Andrew E; Gaoatswe, Gadintshware; Lynch, Lydia; Corrigan, Michelle A; Woods, Conor; O'Connell, Jean; O'Shea, Donal

    2014-04-01

    Glucagon-like peptide 1 (GLP-1) is a gut hormone used in the treatment of type 2 diabetes mellitus. There is emerging evidence that GLP-1 has anti-inflammatory activity in humans, with murine studies suggesting an effect on macrophage polarisation. We hypothesised that GLP-1 analogue therapy in individuals with type 2 diabetes mellitus would affect the inflammatory macrophage molecule soluble CD163 (sCD163) and adipocytokine profile. We studied ten obese type 2 diabetes mellitus patients starting GLP-1 analogue therapy at a hospital-based diabetes service. We investigated levels of sCD163, TNF-α, IL-1β, IL-6, adiponectin and leptin by ELISA, before and after 8 weeks of GLP-1 analogue therapy. GLP-1 analogue therapy reduced levels of the inflammatory macrophage activation molecule sCD163 (220 ng/ml vs 171 ng/ml, p < 0.001). This occurred independent of changes in body weight, fructosamine and HbA1c. GLP-1 analogue therapy was associated with a decrease in levels of the inflammatory cytokines TNF-α (264 vs 149 pg/ml, p < 0.05), IL-1β (2,919 vs 748 pg/ml, p < 0.05) and IL-6 (1,379 vs 461 pg/ml p < 0.05) and an increase in levels of the anti-inflammatory adipokine adiponectin (4,480 vs 6,290 pg/ml, p < 0.002). In individuals with type 2 diabetes mellitus, GLP-1 analogue therapy reduces the frequency of inflammatory macrophages. This effect is not dependent on the glycaemic or body weight effects of GLP-1.

  9. Receptor targeting of hemoglobin mediated by the haptoglobins

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Moestrup, Søren Kragh

    2009-01-01

    Haptoglobin, the haptoglobin-hemoglobin receptor CD163, and the heme oxygenase-1 are proteins with a well-established function in the clearance and metabolism of "free" hemoglobin released during intravascular hemolysis. This scavenging system counteracts the potentially harmful oxidative and NO......-scavenging effects associated with "free" hemoglobin, and, furthermore, elicits an anti-inflammatory response. In the late primate evolution, haptoglobin variants with distinct functions have arisen, including haptoglobin polymers and the haptoglobin-related protein. The latter associates with a subspecies of high......-density lipoprotein (HDL) particles playing a crucial role in the innate immunity against certain trypanosome parasites. Recent studies have elucidated this fairly sophisticated immune defense mechanism that takes advantage of a trypanosomal haptoglobin-hemoglobin receptor evolved to supply the parasite with heme...

  10. 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....

  11. Bayesian Mediation Analysis

    OpenAIRE

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to 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 mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  12. 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.

  13. 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…

  14. 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)

  15. Bayesian dynamic mediation analysis.

    Science.gov (United States)

    Huang, Jing; Yuan, Ying

    2017-12-01

    Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Causal mediation analysis with multiple mediators.

    Science.gov (United States)

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  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. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    This study analyzes how a group of ‘mediators’ in a large, multinational company adapted a computer-mediated communication technology (a ‘virtual workspace’) to the organizational context (and vice versa) by modifying features of the technology, providing ongoing support for users, and promoting...... appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology will be established and used in an organization. However, this study also indicates that the process...... of technology-use mediation is more complex and indeterminate than earlier literature suggests. In particular, we want to draw attention to the fact that advanced computer-mediated communication technologies are equivocal and that technology-use mediation consequently requires ongoing sensemaking (Weick 1995)....

  19. 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......In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors...... to the basal transcription machinery. Mediator was initially isolated from Saccharomyces cerevisiae based on its ability to render a RNA polymerase II in vitro transcription system responsive to activators. Additionally, structural studies have revealed striking structural similarities between S. cerevisiae...

  20. 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...

  1. 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...

  2. 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.

  3. Teaching Mediated Public Relations.

    Science.gov (United States)

    Kent, Michael L.

    2001-01-01

    Discusses approaches to teaching a mediated public relations course, emphasizing the World Wide Web. Outlines five course objectives, assignments and activities, evaluation, texts, and lecture topics. Argues that students mastering these course objectives will understand ethical issues relating to media use, using mediated technology in public…

  4. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    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...

  5. The Mediated Transparent Society

    DEFF Research Database (Denmark)

    Backer, Lise

    2001-01-01

    in the mediated transparent society. The paper concludes that, based on these analyses, the mediated panopticism working on the business segment is not an effective disciplinary apparatus, which can guarantee that business corporations are carrying out important ecological or ethical improvements....

  6. 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

  7. The multitalented Mediator complex.

    Science.gov (United States)

    Carlsten, Jonas O P; Zhu, Xuefeng; Gustafsson, Claes M

    2013-11-01

    The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Music, radio and mediatization

    DEFF Research Database (Denmark)

    Michelsen, Morten; Krogh, Mads

    2016-01-01

    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.......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...

  9. 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.

  10. General resonance mediation

    Energy Technology Data Exchange (ETDEWEB)

    McGarrie, Moritz

    2012-07-15

    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 {sigma}(visible {yields} hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  11. Positively deflected anomaly mediation

    International Nuclear Information System (INIS)

    Okada, Nobuchika

    2002-01-01

    We generalize the so-called 'deflected anomaly mediation' scenario to the case where threshold corrections of heavy messengers to the sparticle squared masses are positive. A concrete model realizing this scenario is also presented. The tachyonic slepton problem can be fixed with only a pair of messengers. The resultant sparticle mass spectrum is quite different from that in the conventional deflected anomaly mediation scenario, but is similar to the one in the gauge mediation scenario. The lightest sparticle is mostly B-ino

  12. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    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.

  13. 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.

  14. 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...

  15. 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...

  16. ENVIRONMENTAL CONFLICT MEDIATION

    Directory of Open Access Journals (Sweden)

    GABRIELA G. MIHUT

    2011-04-01

    Full Text Available At a time of global economic crisis followed by resource crisis, a period in which the world seeks alternative resources through eco-investment, environmental conflicts are inevitable. Romania is among the few countries that do not pay enough attention to environmental conflicts and to the advantages to of solving them through mediation procedure. The present paper deals with areas in which conflicts can be applied in environmental mediation and its benefits.

  17. mma: An R Package for Mediation Analysis with Multiple Mediators

    OpenAIRE

    Qingzhao Yu; Bin Li

    2017-01-01

    Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Causal mediation analysis with multiple causally non-ordered mediators.

    Science.gov (United States)

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  3. Mediation analysis with time varying exposures and mediators.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

    2017-06-01

    In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

  4. 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...

  5. Mediated Cultural Memories

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    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...

  6. 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.

  7. 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.

  8. 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

  9. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  10. Mediation analysis with multiple versions of the mediator.

    Science.gov (United States)

    Vanderweele, Tyler J

    2012-05-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

  11. 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

  12. Current Directions in Mediation Analysis

    OpenAIRE

    MacKinnon, David P.; Fairchild, Amanda J.

    2009-01-01

    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.

  13. Dissociation in mediation

    Directory of Open Access Journals (Sweden)

    Daniela Muraru

    2008-01-01

    Full Text Available This paper approaches several texts that are part of the so-called discourse of mediation, adopting a pragma-dialectical perspective of the theory of dissociation. It is an attempt to identify the uses of dissociative patterns, with special emphasis on the indicators of dissociation. The paper investigates the various uses of the concept of dissociation as a discursive technique in the argumentation on the different aspects that are involved in international conflict, such as the discussion of the notion of peace. The purpose is to identify the role of dissociation, as a device strategically used by the mediator to help the parties minimize the disagreement space, and come to a conflict resolution.

  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. The Mediatization of Philanthropy

    OpenAIRE

    Mitchell, Matthew

    2014-01-01

    This study seeks to better understand the motivations and mechanics of individuals contributing to nonprofits organizations today.  Through the prism of our highly mediatized (Hjarvard, 2008) social environment, this study examines the individual motivations and actions of cause-champions running in the 2013 NYC marathon and fundraising through social media and offline on behalf of the Michael J Fox Foundation (MJFF).  To gain the necessary detail and understanding of these micro-actions of a...

  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. mma: An R Package for Mediation Analysis with Multiple Mediators

    Directory of Open Access Journals (Sweden)

    Qingzhao Yu

    2017-04-01

    Full Text Available Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous, exposure, or mediation variables. With these definitions, multiple mediators of different types can be considered simultaneously, and the indirect effects carried by individual mediators can be separated from the total effect. Moreover, the derived mediation analysis can be performed with general predictive models. That is, the relationships among variables can be modeled using not only generalized linear models but also nonparametric models such as the Multiple Additive Regression Trees. Therefore, more complicated variable transformations and interactions can be considered in analyzing the mediation effects. The proposed method is realized by the R package 'mma'. We illustrate in this paper the proposed method and how to use 'mma' to estimate mediation effects and make inferences.

  19. Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Yang, Hwai-I

    2017-05-01

    Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

  20. 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.

  1. 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...

  2. Porcine, murine and human sialoadhesin (Sn/Siglec-1/CD169): portals for porcine reproductive and respiratory syndrome virus entry into target cells.

    Science.gov (United States)

    Van Breedam, Wander; Verbeeck, Mieke; Christiaens, Isaura; Van Gorp, Hanne; Nauwynck, Hans J

    2013-09-01

    Porcine sialoadhesin (pSn; a sialic acid-binding lectin) and porcine CD163 (pCD163) are molecules that facilitate infectious entry of porcine reproductive and respiratory syndrome virus (PRRSV) into alveolar macrophages. In this study, it was shown that murine Sn (mSn) and human Sn (hSn), like pSn, can promote PRRSV infection of pCD163-expressing cells. Intact sialic acid-binding domains are crucial, since non-sialic acid-binding mutants of pSn, mSn and hSn did not promote infection. Endodomain-deletion mutants of pSn, mSn and hSn promoted PRRSV infection less efficiently, but also showed markedly reduced expression levels, making further research into the potential role of the Sn endodomain in PRRSV receptor activity necessary. These data further complement our knowledge on Sn as an important PRRSV receptor, and suggest - in combination with other published data - that species differences in the main PRRSV entry mediators Sn and CD163 do not account for the strict host species specificity displayed by the virus.

  3. 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.

  4. 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...

  5. Sociocultural mediators of remembering

    DEFF Research Database (Denmark)

    Wagoner, Brady; Gillespie, Alex

    2014-01-01

    , questioning and deferring contribute to the transformation and conventionalization of the material. These diverse sociocultural mediators are integrated into a partially coherent recollection by participants self-reflecting, or as Bartlett termed it, turning around upon their schemas. We demonstrate...... that this self-reflection is both a social and a psychological process, occurring because participants are responding to their own utterances in the same way that they respond to the utterances of other people. These empirical findings are used to make a case for using discursive data to look not only...

  6. DNA-Mediated Electrochemistry

    Science.gov (United States)

    Gorodetsky, Alon A.; Buzzeo, Marisa C.

    2009-01-01

    The base pair stack of DNA has been demonstrated as a medium for long range charge transport chemistry both in solution and at DNA-modified surfaces. This chemistry is exquisitely sensitive to structural perturbations in the base pair stack as occur with lesions, single base mismatches, and protein binding. We have exploited this sensitivity for the development of reliable electrochemical assays based on DNA charge transport at self-assembled DNA monolayers. Here we discuss the characteristic features, applications, and advantages of DNA-mediated electrochemistry. PMID:18980370

  7. 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.

  8. 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...

  9. Interventional effects for mediation analysis with multiple mediators

    OpenAIRE

    Vansteelandt, Stijn; Daniel, Rhian M.

    2017-01-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

  10. 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.

  11. Mediation Analysis: A Practitioner's Guide.

    Science.gov (United States)

    VanderWeele, Tyler J

    2016-01-01

    This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

  12. A higher form (of) mediation

    International Nuclear Information System (INIS)

    Verlinde, Herman; Wang, L-T; Yavin, Itay; Wijnholt, Martijn

    2008-01-01

    We exhibit a simple and robust mechanism for bulk mediation of supersymmetry breaking between hidden and visible sectors localized on geometrically separated D-branes in type II string theory. The mediation proceeds via RR p-forms that couple via linear Chern-Simons terms to the abelian vector bosons on the branes. From a 4-d low energy perspective, the mechanism reduces to U(1) mediation

  13. Mediating Trust in Terrorism Coverage

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    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.......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...

  14. 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...

  15. The Strategic Mediator

    DEFF Research Database (Denmark)

    Rossignoli, Cecilia; Carugati, Andrea; Mola, Lapo

    2009-01-01

    process. Through the study of services evolving over time we show that, as marketplaces support increasingly complex business processes, the market participants begin to privilege the well connected small number to the convenience of the openness to the entire market. The participants see the marketplace......The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter......-organizational relationships. The interest of this paper is to investigate the shift in the role and evolution of services proposed by e-marketplaces in response to the demands of the market participants. We carried out a longitudinal qualitative field study of an e-marketplace providing the outsourcing of the procurement...

  16. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    Action movies participate in the administration of fear [Virilio, P., 2012. The administration of fear. Translated by Ames Hodges. Los Angeles, CA: Semiotext(e)], and the networked affects of contemporary warfare [Anderson, B., 2013. Targeting affective life from above: morale and airpower. In: P......’ [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...... movies work to dispel fear by producing potency and bolstering resolve. We can thus understand action movies as participating in the biopolitical effects of contemporary warfare. Affect is globalized and intensified through action movies’ aesthetics, with the aim of producing a kind of drone subject...

  17. Den sundhedsfremmende mediator

    DEFF Research Database (Denmark)

    Læssøe, Jeppe

    2009-01-01

      Mediatorer er en relativ ny aktør-type og job-funktion, som passer godt ind i det dynamiske videns- og netværkssamfund. I sundhedsfremmende arbejde med vægt på borgernes deltagelse kan mediatorer spille en nøglerolle. Det er derfor vigtigt begrebsmæssigt at kunne skelne mellem forskellige typer...... 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...

  18. Soluble lymphocytic mediators

    Science.gov (United States)

    Pick, E.

    1974-01-01

    The effect of a number of drugs on the production of macrophage migration inhibitory factor (MIF) by antigen-stimulated sensitized guinea-pig lymph node cells was studied. The drugs were present during the entire culture period and eliminated from supernatants by dialysis. It was found that MIF secretion is inhibited by exogenous dibutyryl cyclic AMP and by theophylline and chlorphenesin, two agents raising the endogenous level of cyclic AMP. On the other hand, isoproterenol, which stimulates cyclic AMP generation in several tissues, did not block MIF production. The formation of the mediator was also suppressed by the microfilament-affecting drug, cytochalasin B. The microtubular disruptive agents, colchicine and vinblastine sulphate, did not influence MIF production. It is concluded that: (a) endogenous cyclic AMP may act as a regulator of MIF production; (b) the activity of contractile microfilaments is probably required for MIF formation; and (c) microtubules are not involved in the secretory process. PMID:4369184

  19. Protein- mediated enamel mineralization

    Science.gov (United States)

    Moradian-Oldak, Janet

    2012-01-01

    Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth. PMID:22652761

  20. Mediating environmental disputes

    Energy Technology Data Exchange (ETDEWEB)

    Lake, L.M.

    1977-09-01

    Environmental disputes and lawsuits are examined. Site-specific disputes focus on visible physical phenomena, such as a power plant or local river, and have an immediacy and intensity about them that make it politically hazardous for public officials to assume responsibility for resolving them. As new precedents in environmental case law become less frequent and the number of disputes increases, alternative processes for environmental conflict resolution, such as third-party intervention, become appropriate. Third-party intervention techniques of fact finding, conflict avoidance, conciliation and mediation have been applied to international, labor, prison, school, racial, and hospital disputes. Underlying concepts are described. Two case studies, the Snoqualmie Dam dispute in Washington and the West Side Highway dispute in New York City, illustrate the basic elements associated with third-party intervention. 1 map, 17 references.

  1. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    do not tend to get a media coverage that matches the EU’s considerable influence on European citizens’ daily lives. This study, which is based on in-depth interviews with European Parliament press officers, concludes that these professionals are indeed attuned to a “media logic......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...

  2. 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.

  3. Anomaly mediation deformed by axion

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Kazunori, E-mail: kazunori@hep-th.phys.s.u-tokyo.ac.jp [Department of Physics, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan); Yanagida, Tsutomu T. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan)

    2013-05-13

    We show that in supersymmetric axion models the axion supermultiplet obtains a sizable F-term due to a non-supersymmetric dynamics and it generally gives the gaugino masses comparable to the anomaly mediation contribution. Thus the gaugino mass relation predicted by the anomaly mediation effect can be significantly modified in the presence of axion to solve the strong CP problem.

  4. 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.

  5. 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.

  6. Practical Guide to Civil Mediation

    CERN Document Server

    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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  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. 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...

  16. 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

  17. Nanoparticle mediated micromotor motion

    Science.gov (United States)

    Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.

    2015-03-01

    In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric field. Both strategies lead to dramatically increased moving velocities, with the highest value reaching ~200 μm s-1. By decreasing the nanoparticles' surface wettability and increasing their catalytic activity, a maximum of a ~10-fold increase in the moving speed of the nanoparticle based micromotor can be achieved. Our results demonstrate the advantages of using nanoparticles in micromotor systems.In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric

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

    OpenAIRE

    Wang, Wei; 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 ...

  19. 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.

  20. 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...

  1. 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...

  2. 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

  3. Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

    Science.gov (United States)

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

    2013-10-30

    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 nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas 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. Copyright © 2013 John Wiley & Sons, Ltd.

  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. Mediation analysis with multiple versions of the mediator

    OpenAIRE

    VanderWeele, Tyler J.

    2012-01-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well defined hypothetical interventions on the mediator. In many settings there may be multiple ways to fix the mediator to a particular value and these different hypothetical interventions may have very different implications for the outcome of interest. In this paper we cons...

  6. Dimensional reduction in anomaly mediation

    International Nuclear Information System (INIS)

    Boyda, Ed; Murayama, Hitoshi; Pierce, Aaron

    2002-01-01

    We offer a guide to dimensional reduction in theories with anomaly-mediated supersymmetry breaking. Evanescent operators proportional to ε arise in the bare Lagrangian when it is reduced from d=4 to d=4-2ε 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

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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…

  1. 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…

  2. 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...

  3. 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...

  4. Neutrality in mediation: an ambiguous ethical value

    OpenAIRE

    Bailey, Paul

    2014-01-01

    Mediator neutrality would appear, by definition, to be a necessary and required ethical principle for all mediators to practice. But what is meant by neutrality in mediation? Is it practically possible to be completely neutral between parties in mediation while at the same time being fair to both of them? This paper attempts to answer these two questions.

  5. 7 CFR 900.108 - Mediator's report.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Mediator's report. 900.108 Section 900.108 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Mediator's report. The mediator, upon the completion of mediation proceedings, shall submit to the...

  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. 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

  8. Gaugino-Assisted Anomaly Mediation

    International Nuclear Information System (INIS)

    Kaplan, David Elazzar; Kribs, Graham D.

    2000-01-01

    We 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, we consider this the simplest working model 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. We identify the main differences in the spectrum between this model and other approaches. We also discuss mechanisms for generating the μ term and constraints on additional bulk fields. (author)

  9. 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 transforma......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...... 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...

  10. 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.

  11. 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.

  12. Radical-Mediated Enzymatic Polymerizations

    Science.gov (United States)

    Zavada, Scott R.; Battsengel, Tsatsral; Scott, Timothy F.

    2016-01-01

    Polymerization reactions are commonly effected by exposing monomer formulations to some initiation stimulus such as elevated temperature, light, or a chemical reactant. Increasingly, these polymerization reactions are mediated by enzymes―catalytic proteins―owing to their reaction efficiency under mild conditions as well as their environmental friendliness. The utilization of enzymes, particularly oxidases and peroxidases, for generating radicals via reduction-oxidation mechanisms is especially common for initiating radical-mediated polymerization reactions, including vinyl chain-growth polymerization, atom transfer radical polymerization, thiol–ene step-growth polymerization, and polymerization via oxidative coupling. While enzyme-mediated polymerization is useful for the production of materials intended for subsequent use, it is especially well-suited for in situ polymerizations, where the polymer is formed in the place where it will be utilized. Such polymerizations are especially useful for biomedical adhesives and for sensing applications. PMID:26848652

  13. Mediatization Theory and Digital Media

    DEFF Research Database (Denmark)

    Finnemann, Niels Ole

    2011-01-01

    In the 20th century, the term "media logic" was introduced to denote the influence of independent mass media on political systems and other institutions. In recent years the idea has been reworked and labelled "mediatization" to widen the framework by including new media and new areas of applicat......In the 20th century, the term "media logic" was introduced to denote the influence of independent mass media on political systems and other institutions. In recent years the idea has been reworked and labelled "mediatization" to widen the framework by including new media and new areas...

  14. Surfactant-Mediated Growth Revisited

    International Nuclear Information System (INIS)

    Meyerheim, H. L.; Sander, D.; Popescu, R.; Pan, W.; Kirschner, J.; Popa, I.

    2007-01-01

    The x-ray structure analysis of the oxygen-surfactant-mediated growth of Ni on Cu(001) identifies up to 0.15 monolayers of oxygen in subsurface octahedral sites. This questions the validity of the general view that surfactant oxygen floats on top of the growing Ni film. Rather, the surfactant action is ascribed to an oxygen-enriched zone extending over the two topmost layers. Surface stress measurements support this finding. Our results have important implications for the microscopic understanding of surfactant-mediated growth and the change of the magnetic anisotropy of the Ni films

  15. 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.

  16. 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.

  17. Dynamical Messengers for Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Hook, Anson; Torroba, Gonzalo; /SLAC /Stanford U., Phys. Dept.

    2011-08-17

    We construct models of indirect gauge mediation where the dynamics responsible for breaking supersymmetry simultaneously generates a weakly coupled subsector of messengers. This provides a microscopic realization of messenger gauge mediation where the messenger and hidden sector fields are unified into a single sector. The UV theory is SQCD with massless and massive quarks plus singlets, and at low energies it flows to a weakly coupled quiver gauge theory. One node provides the primary source of supersymmetry breaking, which is then transmitted to the node giving rise to the messenger fields. These models break R-symmetry spontaneously, produce realistic gaugino and sfermion masses, and give a heavy gravitino.

  18. Regulatory T cells in induced sputum of asthmatic children: association with inflammatory cytokines

    Directory of Open Access Journals (Sweden)

    Hamzaoui Agnès

    2010-02-01

    Full Text Available Abstract Background and objective CD4+CD25+ regulatory T (Treg cells play an essential role in maintaining immune homeostasis. In this study, we investigated whether the induced sputum (IS pool and the function of CD4+CD25+ Treg cells are altered in asthma pediatric patients. Methods Treg activity was studied in the IS of 40 asthmatic children. CD3+ cells were analyzed for the expression of FoxP3 mRNA by real time reverse transcription-polymerase chain reaction (RT-PCR. IS cells from asthmatics and controls were stained for Treg markers and analyzed by flow cytometry. We also studied the ability of Treg cells to differentiate monocytes toward alternatively activated macrophages (AAM, and to suppress proinflammatory cytokines. Results (i Mild and moderate asthmatics had significantly decreased expression of FoxP3/β-actin mRNA and decreased proportions of CD4+CD25highFoxP3+ cells compared to healthy children; (ii patients with moderate asthma had even lower proportions of FoxP3 expression compared to mild asthmatic patients; (iii monocytes cultured with Treg cells displayed typical features of AAM, including up-regulated expression of CD206 (macrophage mannose receptor and CD163 (hemoglobin scavenger receptor, and an increased production of chemokine ligand 18 (CCL18. In addition, Treg cells from asthmatics have a reduced capacity to suppress LPS-proinflammatory cytokine production from monocytes/macrophages (IL-1, IL-6 and TNF-α. Conclusion Asthma pediatric patients display a decreased bronchial Treg population. The impaired bronchial Treg activity is associated with disease severity.

  19. Mediating Multilingual Children's Language Resources

    Science.gov (United States)

    Potts, D.; Moran, M. J.

    2013-01-01

    The everyday reality of children's multilingualism is a significant resource for expanding students' perspectives on the world, but many questions remain regarding the negotiation of these resources in mainstream classrooms. Drawing on research from a long-term Canadian study of multiliterate pedagogies, this paper explores mediation of home…

  20. Trilinear-augmented gaugino mediation

    DEFF Research Database (Denmark)

    Heisig, Jan; Kersten, Jörn; Murphy, Nick

    2017-01-01

    We consider a gaugino-mediated supersymmetry breaking scenario where in addition to the gauginos the Higgs fields couple directly to the field that breaks supersymmetry. This yields non-vanishing trilinear scalar couplings in general, which can lead to large mixing in the stop sector providing...

  1. Anomaly mediation in superstring theory

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Joseph P. [Rudolf Peierls Center for Theoretical Physics, Oxford (United Kingdom); Balliol College, Oxford (United Kingdom); Goodsell, Mark [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Palti, Eran [Centre de Physique Theoretique, Ecole Polytechnique, CNRS, Palaiseau (France)

    2010-08-15

    We study anomaly mediated supersymmetry breaking in type IIB string theory and use our results to test the supergravity formula for anomaly mediated gaugino masses. We compute 1-loop gaugino masses for models of D3-branes on orbifold singularities with 3-form fluxes by calculating the annulus correlator of 3-form flux and two gauginos in the zero momentum limit. Consistent with supergravity expectations we find both anomalous and running contributions to 1-loop gaugino masses. For background Neveu-Schwarz H-flux we find an exact match with the supergravity formula. For Ramond-Ramond flux there is an off-shell ambiguity that precludes a full matching. The anomaly mediated gaugino masses, while determined by the infrared spectrum, arise from an explicit sum over UV open string winding modes. We also calculate brane-to-brane tree-level gravity mediated gaugino masses and show that there are two contributions coming from the dilaton and from the twisted modes, which are suppressed by the full T{sup 6} volume and the untwisted T{sup 2} volume respectively. (orig.)

  2. Sonic mediations: body, sound, technology

    NARCIS (Netherlands)

    Birdsall, C.; Enns, A.

    2008-01-01

    Sonic Mediations: Body, Sound, Technology is a collection of original essays that represents an invaluable contribution to the burgeoning field of sound studies. While sound is often posited as having a bridging function, as a passive in-between, this volume invites readers to rethink the concept of

  3. Diselenolane-mediated cellular uptake.

    Science.gov (United States)

    Chuard, Nicolas; Poblador-Bahamonde, Amalia I; Zong, Lili; Bartolami, Eline; Hildebrandt, Jana; Weigand, Wolfgang; Sakai, Naomi; Matile, Stefan

    2018-02-21

    The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.

  4. Mediated Encryption: Analysis and Design

    Directory of Open Access Journals (Sweden)

    I. Elashry1

    2015-01-01

    Full Text Available Boneh, Ding and Tsudik presented identity-based mediated RSA encryption and signature systems in which the users are not allowed to decrypt/sign messages without the authorisation of a security mediator.We show that ID-MRSA is not secure and we present a secure modified version of it which is as efficient as the original system. We also propose a generic mediated encryption that translates any identity based encryption to a mediated version of this IBE. It envelops an IBE encrypted message using a user’s identity into an IBE envelope using the identity of the SEM. We present two security models based on the role of the adversary whether it is a revoked user or a hacked SEM. We prove that GME is as secure as the SEM’s IBE against a revoked user and as secure as the user’s IBE against a hacked SEM. We also present two implementations of GME based on Boneh-Franklin FullIBE system which is a pairing-based system and Boneh, Gentry and Hamburg (BGH system which is pairing-free system.

  5. Crime fiction and mediatized religion

    DEFF Research Database (Denmark)

    Hansen, Kim Toft

    Scandinavian media where religion has become mediatized. Consumers of popular culture no longer endorse confidence in institutionalized religion, but that does not mean that people are losing faith: Faith only seems to adjust itself and tiptoe into popular media and popular fiction. Hence, this paper seeks...

  6. 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.

  7. Profession of mediator as the professional provider of the mediation process

    Directory of Open Access Journals (Sweden)

    Jernej Šoštar

    2017-03-01

    Full Text Available The civil mediation programme, which is a court-connected programme, established as a form of alternative dispute resolution, is increasingly gaining ground as a field with its own theoretical and practical knowledge, principles and basic rules. Mediation has already set up its own body of knowledge, based on studies, classification of cases and the analyses of the results. In this article, we examine whether in the context of the development of mediation in Slovenia we might already talk about the profession of the mediator, defined as a provider of the mediation process. We examine the court-connected civil mediation and mediators who mediate at the court-connected civil mediation, and define them theoretically. By interviewing the mediation experts and mediators we examine their opinions about mediators and the court mediation. We examine the legal basis for the court-connected mediation programmes in Slovenia as well as in the European Union. Proceeding from our findings we conclude that the legal regulation of the court mediation in Slovenia is well established, and that the mediators of the court-connected civil mediation programmes can be accepted as the professional providers of the mediation process.

  8. Ratio-of-Mediator-Probability Weighting for Causal Mediation Analysis in the Presence of Treatment-by-Mediator Interaction

    Science.gov (United States)

    Hong, Guanglei; Deutsch, Jonah; Hill, Heather D.

    2015-01-01

    Conventional methods for mediation analysis generate biased results when the mediator--outcome relationship depends on the treatment condition. This article shows how the ratio-of-mediator-probability weighting (RMPW) method can be used to decompose total effects into natural direct and indirect effects in the presence of treatment-by-mediator…

  9. Mediation Works: An Action Research Study Evaluating the Peer Mediation Program from the Eyes of Mediators and Faculty

    Science.gov (United States)

    Cook, Jacqueline Yvonne; Boes, Susan R.

    2013-01-01

    A literature review was conducted to understand how mediators and faculty view a Peer Mediation Program (PMP). The review identified four subgroups: mediators, teachers, administrators, and school counselors as well as their views on the success or lack of success of PMPs. The research also reflects how to best engage stakeholders in the mediation…

  10. Parameter space of general gauge mediation

    International Nuclear Information System (INIS)

    Rajaraman, Arvind; Shirman, Yuri; Smidt, Joseph; Yu, Felix

    2009-01-01

    We study a subspace of General Gauge Mediation (GGM) models which generalize models of gauge mediation. We find superpartner spectra that are markedly different from those of typical gauge and gaugino mediation scenarios. While typical gauge mediation predictions of either a neutralino or stau next-to-lightest supersymmetric particle (NLSP) are easily reproducible with the GGM parameters, chargino and sneutrino NLSPs are generic for many reasonable choices of GGM parameters.

  11. Mediation Analysis in Psychosomatic Medicine Research

    OpenAIRE

    Lockhart, Ginger; MacKinnon, David P.; Ohlrich, Vanessa

    2010-01-01

    This article presents an overview of statistical mediation analysis and its application to psychosomatic medicine research. The article begins with a description of the major approaches to mediation analysis and an evaluation of the strengths and limits of each. Emphasis is placed on longitudinal mediation models, and an application using latent growth modeling is presented. The article concludes with a description of recent developments in mediation analysis and suggestions for the use of me...

  12. Mediator oxidation systems in organic electrosynthesis

    International Nuclear Information System (INIS)

    Ogibin, Yurii N; Elinson, Michail N; Nikishin, Gennady I

    2009-01-01

    The data on the use of mediator oxidation systems activated by electric current (anodic or parallel anodic and cathodic) in organic electrosynthesis are considered and generalised. Electrochemical activation of these systems permits successful application of catalytic versions and easy scaling of mediator-promoted processes. Chemical and environmental advantages of electrochemical processes catalysed by mediator oxidation systems are demonstrated. Examples of the application of organic and inorganic mediators for the oxidation of various classes of organic compounds under conditions of electrolysis are given.

  13. LEGAL CULTURES AND MEDIATION. INTERACTIONS AND EVOLUTIONS

    Directory of Open Access Journals (Sweden)

    Claudiu Ramon D. BUTCULESCU

    2014-05-01

    Full Text Available Mediation, as an alternative dispute resolution method, is closely connected with the system of legal cultures. Mediation is an important link between legal culture and the judicial system. Mediation also acts as an interface between internal legal culture and external legal culture. This paper addresses the issues regarding the links and interactions between mediation and legal cultures, as well as the effects that arise from these interactions.

  14. Agrobacterium tumefaciens-Mediated Transformation

    DEFF Research Database (Denmark)

    Frandsen, Rasmus John Normand

    2015-01-01

    The use of Agrobacterium tumefaciens-mediated transformation for achieving genetic transformation of fungi has steadily increased over the last decade, and has proven to be almost universally applicable technique once suitable selection markers have been developed. In recent years the major...... technical advances has been made within the initial steps of the process, more specifically the efficient construction of plasmids for performing targeted genome modifications. This chapter provides a generic protocol for performing genetic transformation of ascomycetes via A. tumefaciens......-mediated transformation (AMT) and guidelines for optimizing the AMT process with new fungal species. The chapter also includes a highly efficient vector construction system based on Uracil Specific Excisions Reagent (USER) cloning and specific PCR generated building blocks, which can be combined ad hoc to create complex...

  15. Introduction: Mediating and Remediating Death

    DEFF Research Database (Denmark)

    Christensen, Dorthe Refslund; Sandvik, Kjetil

    2014-01-01

    In this second volume we explore how people, groups and institutions deal with death through processes of mediation (the presentation of something through media), remediation (the representation of one medium in another, see below) and mediatization (the process through which core elements...... of a social or cultural activity assume media form, see below). The volume presents a wide variety of ethnographies of death from Norway, Finland, Sweden, the US, Papua New Guinea, Bosnia and Hercegovina, Libya, Tibet, Uganda and Denmark as well as a number of online sites and social media material....... These are analyzed through a vast number of theoretical and analytical perspectives in order to investigate how very diverse practices surrounding death and dying - mourning and commemoration, ritualization, politicization, re-enactment, traditionalization, activism or documentarism: private or public, offline...

  16. Mediatization: a concept, multiple voices

    Directory of Open Access Journals (Sweden)

    Pedro Gilberto GOMES

    2016-12-01

    Full Text Available Mediatization has become increasingly a key concept, fundamental, essential to describe the present and the history of media and communicative change taking place. Thus, it became part of a whole, one can not see them as a separate sphere. In this perspective, the media coverage is used as a concept to describe the process of expansion of the different technical means and consider the interrelationships between the communicative change, means and sociocultural change. However, although many researchers use the concept of mediatization, each gives you the meaning that best suits your needs. Thus, the concept of media coverage is treated with multiple voices. This paper discusses this problem and present a preliminary pre-position on the matter.

  17. 41 CFR 101-8.717 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Mediation. 101-8.717... FINANCIAL ASSISTANCE 8.7-Discrimination Prohibited on the Basis of Age § 101-8.717 Mediation. (a) GSA promptly refers to the mediation agency designated by the Secretary, HHS, all sufficient complaints that...

  18. 34 CFR 303.419 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Mediation. 303.419 Section 303.419 Education... DISABILITIES Procedural Safeguards Mediation and Due Process Procedures for Parents and Children § 303.419 Mediation. (a) General. Each State shall ensure that procedures are established and implemented to allow...

  19. 45 CFR 617.10 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Mediation. 617.10 Section 617.10 Public Welfare... OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE FROM NSF § 617.10 Mediation. (a) NSF will refer to the Federal Mediation and Conciliation Service all complaints that fall within...

  20. 34 CFR 300.506 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Mediation. 300.506 Section 300.506 Education... DISABILITIES Procedural Safeguards Due Process Procedures for Parents and Children § 300.506 Mediation. (a... due process complaint, to resolve disputes through a mediation process. (b) Requirements. The...

  1. Single-Level and Multilevel Mediation Analysis

    Science.gov (United States)

    Tofighi, Davood; Thoemmes, Felix

    2014-01-01

    Mediation analysis is a statistical approach used to examine how the effect of an independent variable on an outcome is transmitted through an intervening variable (mediator). In this article, we provide a gentle introduction to single-level and multilevel mediation analyses. Using single-level data, we demonstrate an application of structural…

  2. 7 CFR 900.109 - Mediation agreement.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Mediation agreement. 900.109 Section 900.109 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Mediation agreement. An agreement arrived at by mediation shall not become effective until approved by the...

  3. The Merits of Using Longitudinal Mediation

    Science.gov (United States)

    Jose, Paul E.

    2016-01-01

    Many of the mediation analyses reported in the literature are based on concurrent or single-occasion data sets. The 2 overarching themes of the present article are: Results of concurrent mediations are inherently ambiguous, and researchers would be wise to conduct mediations on longitudinal data sets instead. An example included here demonstrates…

  4. 13 CFR 117.12 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Mediation. 117.12 Section 117.12... Mediation. (a) SBA shall, after ensuring that the complaint falls within the coverage of this Act and all... clearly within an exception, promptly refer the complaint to the Federal Mediation and Conciliation...

  5. 7 CFR 400.94 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Mediation. 400.94 Section 400.94 Agriculture... AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Appeal Procedure § 400.94 Mediation. For adverse decisions only: (a) Appellants have the right to seek mediation or other forms of alternative dispute resolution in...

  6. Causal Mediation Analysis: Warning! Assumptions Ahead

    Science.gov (United States)

    Keele, Luke

    2015-01-01

    In policy evaluations, interest may focus on why a particular treatment works. One tool for understanding why treatments work is causal mediation analysis. In this essay, I focus on the assumptions needed to estimate mediation effects. I show that there is no "gold standard" method for the identification of causal mediation effects. In…

  7. Methods for Mediation Analysis with Missing Data

    Science.gov (United States)

    Zhang, Zhiyong; Wang, Lijuan

    2013-01-01

    Despite wide applications of both mediation models and missing data techniques, formal discussion of mediation analysis with missing data is still rare. We introduce and compare four approaches to dealing with missing data in mediation analysis including list wise deletion, pairwise deletion, multiple imputation (MI), and a two-stage maximum…

  8. Axino dark matter in mirage mediation

    International Nuclear Information System (INIS)

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

    2009-01-01

    The mirage mediation of supersymmetry breaking is a phenomenologically quite interesting possibility, however, it suffers from two major problems: the moduli-induced gravitino problem and the μ-Bμ problem. In this paper, we propose that the axionic extension of mirage mediation, axionic mirage mediation can solve both problems simultaneously. We address the cosmological consequences of the scenario extensively.

  9. Mediation in complex multi-party disputes

    NARCIS (Netherlands)

    Kamminga, Y.P.; Blohorn-Brenneur, B.

    2013-01-01

    Mediation is on the rise but it is lagging behind in certain fields such as in the resolution of complex disputes. This article addresses how biases in the decision-making process for selecting either mediation or litigation surrounding dispute resolution works in the disadvantage of mediation. It

  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. Minimal ancilla mediated quantum computation

    International Nuclear Information System (INIS)

    Proctor, Timothy J.; Kendon, Viv

    2014-01-01

    Schemes of universal quantum computation in which the interactions between the computational elements, in a computational register, are mediated by some ancillary system are of interest due to their relevance to the physical implementation of a quantum computer. Furthermore, reducing the level of control required over both the ancillary and register systems has the potential to simplify any experimental implementation. In this paper we consider how to minimise the control needed to implement universal quantum computation in an ancilla-mediated fashion. Considering computational schemes which require no measurements and hence evolve by unitary dynamics for the global system, we show that when employing an ancilla qubit there are certain fixed-time ancilla-register interactions which, along with ancilla initialisation in the computational basis, are universal for quantum computation with no additional control of either the ancilla or the register. We develop two distinct models based on locally inequivalent interactions and we then discuss the relationship between these unitary models and the measurement-based ancilla-mediated models known as ancilla-driven quantum computation. (orig.)

  12. Male-mediated developmental toxicity

    Directory of Open Access Journals (Sweden)

    Diana Anderson

    2014-02-01

    Full Text Available Male-mediated developmental toxicity has been of concern for many years. The public became aware of male-mediated developmental toxicity in the early 1990s when it was reported that men working at Sellafield might be causing leukemia in their children. Human and animal studies have contributed to our current understanding of male-mediated effects. Animal studies in the 1980s and 1990s suggested that genetic damage after radiation and chemical exposure might be transmitted to offspring. With the increasing understanding that there is histone retention and modification, protamine incorporation into the chromatin and DNA methylation in mature sperm and that spermatozoal RNA transcripts can play important roles in the epigenetic state of sperm, heritable studies began to be viewed differently. Recent reports using molecular approaches have demonstrated that DNA damage can be transmitted to babies from smoking fathers, and expanded simple tandem repeats minisatellite mutations were found in the germline of fathers who were exposed to radiation from the Chernobyl nuclear power plant disaster. In epidemiological studies, it is possible to clarify whether damage is transmitted to the sons after exposure of the fathers. Paternally transmitted damage to the offspring is now recognized as a complex issue with genetic as well as epigenetic components.

  13. Substrate mediated enzyme prodrug therapy.

    Directory of Open Access Journals (Sweden)

    Betina Fejerskov

    Full Text Available In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol, β-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time - and dose - dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering.

  14. Mediators and Metaphorical Analysis: A Phenomenological Study of Florida Family Court Mediators

    Science.gov (United States)

    Storrow, Rebecca A.

    2012-01-01

    Florida family court mediation programs have typically been assessed with quantitative analysis. To understand the complexity of the experience of being a family mediator, it was necessary to explore how mediators practiced through qualitative research. Metaphors have been considered to be representations of mediators' mental models regarding…

  15. Mediation – Mandatory Information and Facultative Applicability

    Directory of Open Access Journals (Sweden)

    Monica Pocora

    2015-12-01

    Full Text Available Considering that mediation is a facilitating way to access the alternative solving of litigations in conciliatory terms, the study is encouraging using the mediation and providing a balanced relationship between mediation and judiciary procedures. As an aftermath of summary definition, we can say that role of mediation is to overcome the communicative barriers in order to solve the conflict and save the fact situation on both parts. The study aims at analyzing objectively all consequences of both solving ways of litigations: traditional one, through the law court and mediation, with the advantages derived from them (celerity vs. time consuming, expensive judiciary proceedings vs. low costs, etc.

  16. Immunoglobulin E-Mediated Autoimmunity

    Directory of Open Access Journals (Sweden)

    Marcus Maurer

    2018-04-01

    Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

  17. 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

  18. Mediated electrochemical hazardous waste destruction

    International Nuclear Information System (INIS)

    Hickman, R.G.; Farmer, J.C.; Wang, F.T.

    1992-03-01

    There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing an electrochemical process, based upon mediated electrochemical oxidation (MEO), that converts toxic organic components of mixed waste to water, carbon dioxide, and chloride or chloride precipitates. Aggressive oxidizer ions such as Ag 2+ , Co 3+ , or Fe 3+ are produced at an anode. These can attack organic molecules directly, and may also produce hydroxyl free radicals that promote destruction. Solid and liquid radioactive waste streams containing only inorganic radionuclide forms may be treated with existing technology and prepared for final disposal. The coulombic efficiency of the process has been determined, as well as the destruction efficiency for ethylene glycol, a surrogate waste. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient- temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag(II) has been used as a mediator in this process. Fe(III) and Co(III) are attractive alternatives to Ag(II) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is toxic heavy metal. Quantitative data have been obtained for the complete oxidation of ethylene glycol by Fe(III) and Co(III). Though ethylene glycol is a nonhalogenated organic, these data have enabled us to make direct comparisons of activities of Fe(III) and Co(III) with Ag(II). Very good quantitative data for the oxidation of ethylene glycol by Ag(II) had already been collected

  19. Mediation for resolving family disputes

    Directory of Open Access Journals (Sweden)

    Kamenecka-Usova M.

    2016-01-01

    Full Text Available Nowadays the understanding of the institute of marriage and its importance in the society has changed. Marriage is no longer assumed to be a commitment for a lifetime. As the principle of equality has replaced hierarchy as the guiding principle of family law it gave more grounds for family disputes and it became socially acceptable to leave marriages that are intolerable or merely unfulfilling. The aim of this article is to suggest an alternative dispute resolution method-mediation as a worthy option for resolving family conflicts.

  20. Trilinear-augmented gaugino mediation

    Energy Technology Data Exchange (ETDEWEB)

    Heisig, Jan [Institute for Theoretical Particle Physics and Cosmology, RWTH Aachen University,52056 Aachen (Germany); Kersten, Jörn [Department of Physics and Technology, University of Bergen,5020 Bergen (Norway); Murphy, Nick [CP-Origins, University of Southern Denmark,5230 Odense M (Denmark); Strümke, Inga [Department of Physics and Technology, University of Bergen,5020 Bergen (Norway)

    2017-05-02

    We consider a gaugino-mediated supersymmetry breaking scenario where in addition to the gauginos the Higgs fields couple directly to the field that breaks supersymmetry. This yields non-vanishing trilinear scalar couplings in general, which can lead to large mixing in the stop sector providing a sufficiently large Higgs mass. Using the most recent release of FeynHiggs, we show the implications on the parameter space. Assuming a gravitino LSP, we find allowed points with a neutralino, sneutrino or stau NLSP. We test these points against the results of Run 1 of the LHC, considering in particular searches for heavy stable charged particles.

  1. Trilinear-augmented gaugino mediation

    International Nuclear Information System (INIS)

    Heisig, Jan; Kersten, Jörn; Murphy, Nick; Strümke, Inga

    2017-01-01

    We consider a gaugino-mediated supersymmetry breaking scenario where in addition to the gauginos the Higgs fields couple directly to the field that breaks supersymmetry. This yields non-vanishing trilinear scalar couplings in general, which can lead to large mixing in the stop sector providing a sufficiently large Higgs mass. Using the most recent release of FeynHiggs, we show the implications on the parameter space. Assuming a gravitino LSP, we find allowed points with a neutralino, sneutrino or stau NLSP. We test these points against the results of Run 1 of the LHC, considering in particular searches for heavy stable charged particles.

  2. Mediation designs for tobacco prevention research

    Science.gov (United States)

    MacKinnon, David P.; Taborga, Marcia P.; Morgan-Lopez, Antonio A.

    2010-01-01

    This paper describes research designs and statistical analyses to investigate how tobacco prevention programs achieve their effects on tobacco use. A theoretical approach to program development and evaluation useful for any prevention program guides the analysis. The theoretical approach focuses on action theory for how the program affects mediating variables and on conceptual theory for how mediating variables are related to tobacco use. Information on the mediating mechanisms by which tobacco prevention programs achieve effects is useful for the development of efficient programs and provides a test of the theoretical basis of prevention efforts. Examples of these potential mediating mechanisms are described including mediated effects through attitudes, social norms, beliefs about positive consequences, and accessibility to tobacco. Prior research provides evidence that changes in social norms are a critical mediating mechanism for successful tobacco prevention. Analysis of mediating variables in single group designs with multiple mediators are described as well as multiple group randomized designs which are the most likely to accurately uncover important mediating mechanisms. More complicated dismantling and constructive designs are described and illustrated based on current findings from tobacco research. Mediation analysis for categorical outcomes and more complicated statistical methods are outlined. PMID:12324176

  3. The Mediator complex and transcription regulation

    Science.gov (United States)

    Poss, Zachary C.; Ebmeier, Christopher C.

    2013-01-01

    The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

  4. Transporter-mediated biofuel secretion.

    Science.gov (United States)

    Doshi, Rupak; Nguyen, Tuan; Chang, Geoffrey

    2013-05-07

    Engineering microorganisms to produce biofuels is currently among the most promising strategies in renewable energy. However, harvesting these organisms for extracting biofuels is energy- and cost-intensive, limiting the commercial feasibility of large-scale production. Here, we demonstrate the use of a class of transport proteins of pharmacological interest to circumvent the need to harvest biomass during biofuel production. We show that membrane-embedded transporters, better known to efflux lipids and drugs, can be used to mediate the secretion of intracellularly synthesized model isoprenoid biofuel compounds to the extracellular milieu. Transporter-mediated biofuel secretion sustainably maintained an approximate three- to fivefold boost in biofuel production in our Escherichia coli test system. Because the transporters used in this study belong to the ubiquitous ATP-binding cassette protein family, we propose their use as "plug-and-play" biofuel-secreting systems in a variety of bacteria, cyanobacteria, diatoms, yeast, and algae used for biofuel production. This investigation showcases the potential of expressing desired membrane transport proteins in cell factories to achieve the export or import of substances of economic, environmental, or therapeutic importance.

  5. Multifunctional Curcumin Mediate Multitherapeutic Effects.

    Science.gov (United States)

    Shehzad, Adeeb; Qureshi, Munibah; Anwar, Muhammad Nabeel; Lee, Young Sup

    2017-09-01

    Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases. Numerous studies have shown that curcumin modulate multiple molecular targets and can be translated to the clinics for multiple therapeutic processes. There is compelling evidence that curcumin can block cell proliferation, invasion, and angiogenesis as well as reduced the prolonged survival of cancer cells. Curcumin mediates anti-inflammatory effect through downregulation of inflammatory cytokines, transcription factors, protein kinases, and enzymes that promote inflammation and development of chronic diseases. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways by activating caspase cascades. Curcumin is a safe and nontoxic drug that has been reported to be well tolerated. Available clinical trials support the potential role of curcumin for treatment of various inflammatory disorders. However, curcumin's efficacy is hindered by poor absorption and low bioavailability, which limit its translation into clinics. This review outlines the potential pharmacological and clinical role of curcumin, which provide a gateway for the beneficial role of plant isolated compounds in treatment of various inflammatory diseases and cancer. © 2017 Institute of Food Technologists®.

  6. Desperately Trying to Mediate Immediacy

    Directory of Open Access Journals (Sweden)

    Andreas Oliver Schellewald

    2018-01-01

    Full Text Available Evermore aspects of contemporary cultures, societies and human life appear to be changed through processes of digitization and mediatization. A great body of work is touching on these processes of change. However, not many discuss aspects of leisure and aesthetics. And if they do so, seldom regarding bodily and worldly aspects. This paper thus seeks to discuss such changes alongside the phenomenon of esports. More precisely, the paper situates the aesthetic dimension and practices of watching and doing esports in contemporary cultures and societies, focusing on lived experiences (ästhetisches Erleben in digital and mediated contexts. The failing attempt to understand, the attempt to re-present and Gelassenheit (composure or serenity are introduced as modes of coping with immediate aesthetic experiences. Here, especially the constitutive transition from a physical to a meta-physical dimension of reality will be grasped on. By that, ongoing philosophical debates about the constitution of reality and being can be supported in their progress.

  7. Direct detection with dark mediators

    Energy Technology Data Exchange (ETDEWEB)

    Curtin, David; Surujon, Ze' ev [C. N. Yang Institute for Theoretical Physics, Stony Brook University, Stony Brook, NY 11794 (United States); Tsai, Yuhsin [Physics Department, University of California Davis, Davis, CA 95616 (United States)

    2014-11-10

    We introduce dark mediator Dark Matter (dmDM) where the dark and visible sectors are connected by at least one light mediator ϕ carrying the same dark charge that stabilizes DM. ϕ is coupled to the Standard Model via an operator q{sup ¯}qϕϕ{sup ⁎}/Λ, and to dark matter via a Yukawa coupling y{sub χ}χ{sup c¯}χϕ. Direct detection is realized as the 2→3 process χN→χ{sup ¯}Nϕ at tree-level for m{sub ϕ}≲10 keV and small Yukawa coupling, or alternatively as a loop-induced 2→2 process χN→χN. We explore the direct-detection consequences of this scenario and find that a heavy O(100 GeV) dmDM candidate fakes different O(10 GeV) standard WIMPs in different experiments. Large portions of the dmDM parameter space are detectable above the irreducible neutrino background and not yet excluded by any bounds. Interestingly, for the m{sub ϕ} range leading to novel direct detection phenomenology, dmDM is also a form of Self-Interacting Dark Matter (SIDM), which resolves inconsistencies between dwarf galaxy observations and numerical simulations.

  8. Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

    Science.gov (United States)

    Otterdal, Kari; Janardhanan, Jeshina; Astrup, Elisabeth; Ueland, Thor; Prakash, John A J; Lekva, Tove; Abraham, O C; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M

    2014-11-01

    Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome. Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls (n = 31), both in the acute phase and after recovery, by enzyme immunoassays. Patients had markedly elevated levels of all mediators in the acute phase, differing from both healthy and infectious disease controls. During follow-up levels of ALCAM, VCAM-1, sCD14 and YKL-40 remained elevated compared to levels in healthy controls. High plasma ALCAM, VCAM-1, sCD163, sCD14, and MIF, and in particular YKL-40 were all associated with disease severity and ALCAM, sCD163, MIF and especially YKL-40, were associated with mortality. Our findings show that scrub typhus is characterized by elevated levels of monocyte/macrophage and endothelial related markers. These inflammatory markers, and in particular YKL-40, may contribute to disease severity and clinical outcome. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  9. Robust Mediation Analysis Based on Median Regression

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2014-01-01

    Mediation analysis has many applications in psychology and the social sciences. The most prevalent methods typically assume that the error distribution is normal and homoscedastic. However, this assumption may rarely be met in practice, which can affect the validity of the mediation analysis. To address this problem, we propose robust mediation analysis based on median regression. Our approach is robust to various departures from the assumption of homoscedasticity and normality, including heavy-tailed, skewed, contaminated, and heteroscedastic distributions. Simulation studies show that under these circumstances, the proposed method is more efficient and powerful than standard mediation analysis. We further extend the proposed robust method to multilevel mediation analysis, and demonstrate through simulation studies that the new approach outperforms the standard multilevel mediation analysis. We illustrate the proposed method using data from a program designed to increase reemployment and enhance mental health of job seekers. PMID:24079925

  10. Legal and Psychological Aspects of Mediation

    Directory of Open Access Journals (Sweden)

    Dobrokhotova E. N.

    2016-01-01

    Full Text Available The article focuses on gradual innovation of mediation into the practice of social conflict resolution in the light of legal and psychological means of mediation. While mediation is perceived as a conflictological concept and is more widely used in dispute settlement and resolution, a new interdisciplinary field of theoretical knowledge with its own conceptual framework as well as a new professional and practical field are beginning to form both in Russia and in other countries. As theoretical and practical aspects of innovation in mediation require consolidation not only for its national development but also for the guaranteed international cooperation, the article touches upon some of the particular theoretical issues of the topic in question: terminological consistency, consolidation of the system of mediation principles, the phenomenon of juridisation of mediation and its limits.

  11. Regulation of metabolism by the Mediator complex.

    Science.gov (United States)

    Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

    2016-01-01

    The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

  12. DISTANCE LEARNERSÕ PERCEPTIONS OF COMPUTER MEDIATED COMMUNICATION

    OpenAIRE

    Mujgan Bozkaya; Irem Erdem Aydin

    2011-01-01

    In this study, perspectives of the first year students in the completely online Information Management Associate Degree Program at Anadolu University regarding computer as a communication medium were investigated. StudentsÕ perspectives on computer-mediated communications were analyzed in the light of three different views in the area of computer-mediated communications: The first view suggests that face-to-face settings are better communication environments compared to computer-mediated envi...

  13. Community Mediation. A Model for Romania

    Directory of Open Access Journals (Sweden)

    Christian Radu CHEREJI

    2014-02-01

    Full Text Available Community mediation takes all forms and shapes all over the world. In order to better understand its limitations in adapting to different contexts, we have compared the evolution of community mediation services in two totally different systems, USA and Sri Lanka. Based on this analysis and the results of a research conducted in Cluj-Napoca in the fall of 2013, we have recommended a community mediation model suitable for the current Romanian social, economic and cultural framework.

  14. Parental mediation and cyberbullying - a longitudinal study.

    Science.gov (United States)

    Chng, Grace S; Liau, Albert; Khoo, Angeline; Li, Dongdong

    2014-01-01

    Parents use active and restrictive mediation strategies to guide and regulate children's online participation and the online risks they encounter. However, changes in parental mediation do occur over time and the effectiveness of these strategies on cyberbullying demands for further empirical investigation. The current study addresses these issues with a sample of 1084 students (49% girls) in a longitudinal, three-wave design. Gender differences were tested via multi-group analyses. Longitudinal growth models showed that parental use of both active and restrictive mediation decreased over time. For both types of mediation, the mean rate of change had a significant effect on boys' engagement in cyberbullying, but not for girls. Initial levels of restrictive mediation, but not active mediation, were found to be significantly predictive of cyberbullying in both genders. Girls had higher initial levels of both parental mediation types in comparison to boys. The results reveal that the effectiveness of active and restrictive mediation in relation to students' cyberbullying differs and informs us on gender differences. The implications of these results for parental education in online mediation are discussed.

  15. Digital methods for mediated discourse analysis

    DEFF Research Database (Denmark)

    Kjær, Malene; Larsen, Malene Charlotte

    2015-01-01

    , restrictions or privately mediated settings. Having used mediated discourse analysis (Scollon 2002, Scollon & Scollon, 2004) as a framework in two different research projects, we show how the framework, in correlation with digital resources for data gathering, provides new understandings of 1) the daily......In this paper we discuss methodological strategies for collecting multimodal data using digital resources. The aim is to show how digital resources can provide ethnographic insights into mediated actions (Scollon, 2002) that can otherwise be difficult to observe or engage in, due to, for instance......) and online questionnaire data in order to capture mediated actions and discourses in practice....

  16. Transcription regulation by the Mediator complex.

    Science.gov (United States)

    Soutourina, Julie

    2018-04-01

    Alterations in the regulation of gene expression are frequently associated with developmental diseases or cancer. Transcription activation is a key phenomenon in the regulation of gene expression. In all eukaryotes, mediator of RNA polymerase II transcription (Mediator), a large complex with modular organization, is generally required for transcription by RNA polymerase II, and it regulates various steps of this process. The main function of Mediator is to transduce signals from the transcription activators bound to enhancer regions to the transcription machinery, which is assembled at promoters as the preinitiation complex (PIC) to control transcription initiation. Recent functional studies of Mediator with the use of structural biology approaches and functional genomics have revealed new insights into Mediator activity and its regulation during transcription initiation, including how Mediator is recruited to transcription regulatory regions and how it interacts and cooperates with PIC components to assist in PIC assembly. Novel roles of Mediator in the control of gene expression have also been revealed by showing its connection to the nuclear pore and linking Mediator to the regulation of gene positioning in the nuclear space. Clear links between Mediator subunits and disease have also encouraged studies to explore targeting of this complex as a potential therapeutic approach in cancer and fungal infections.

  17. Computer-Mediated Communication Systems

    Directory of Open Access Journals (Sweden)

    Bin Yu

    2011-10-01

    Full Text Available The essence of communication is to exchange and share information. Computers provide a new medium to human communication. CMC system, composed of human and computers, absorbs and then extends the advantages of all former formats of communication, embracing the instant interaction of oral communication, the abstract logics of printing dissemination, and the vivid images of movie and television. It also creates a series of new communication formats, such as Hyper Text, Multimedia etc. which are the information organizing methods, and cross-space message delivering patterns. Benefiting from the continuous development of technique and mechanism, the computer-mediated communication makes the dream of transmitting information cross space and time become true, which will definitely have a great impact on our social lives.

  18. Lepton-flavor violating mediators

    Energy Technology Data Exchange (ETDEWEB)

    Galon, Iftah; Kwa, Anna [Department of Physics & Astronomy, University of California,Irvine, CA 92697 (United States); Tanedo, Philip [Department of Physics & Astronomy, University of California,Riverside, CA 92521 (United States)

    2017-03-13

    We present a framework where dark matter interacts with the Standard Model through a light, spin-0 mediator that couples chirally to pairs of different-flavor leptons. This flavor violating final state weakens bounds on new physics coupled to leptons from terrestrial experiments and cosmic-ray measurements. As an example, we apply this framework to construct a model for the Fermi-LAT excess of GeV γ-rays from the galactic center. We comment on the viability of this portal for self-interacting dark matter explanations of small scale structure anomalies and embeddings in flavor models. Models of this type are shown to be compatible with the muon anomalous magnetic moment anomaly. We review current experimental constraints and identify possible future theoretical and experimental directions.

  19. Phenomenological aspects of mirage mediation

    Energy Technology Data Exchange (ETDEWEB)

    Loewen, Valeri

    2009-07-15

    We consider the possibility that string theory vacua with spontaneously broken supersymmetry and a small positive cosmological constant arise due to hidden sector matter interactions, known as F-uplifting/F-downlifting. We analyze this procedure in a model-independent way in the context of type IIB and heterotic string theory. Our investigation shows that the uplifting/downlifting sector has very important consequences for the resulting phenomenology. Not only does it adjust the vacuum energy, but it can also participate in the process of moduli stabilization. In addition, we find that this sector is the dominant source of supersymmetry breaking. It leads to a hybrid mediation scheme and its signature is a relaxed mirage pattern of the soft supersymmetry breaking terms. The low energy spectra exhibit distinct phenomenological properties and di er from conventional schemes considered so far. (orig.)

  20. Phenomenological aspects of mirage mediation

    International Nuclear Information System (INIS)

    Loewen, Valeri

    2009-07-01

    We consider the possibility that string theory vacua with spontaneously broken supersymmetry and a small positive cosmological constant arise due to hidden sector matter interactions, known as F-uplifting/F-downlifting. We analyze this procedure in a model-independent way in the context of type IIB and heterotic string theory. Our investigation shows that the uplifting/downlifting sector has very important consequences for the resulting phenomenology. Not only does it adjust the vacuum energy, but it can also participate in the process of moduli stabilization. In addition, we find that this sector is the dominant source of supersymmetry breaking. It leads to a hybrid mediation scheme and its signature is a relaxed mirage pattern of the soft supersymmetry breaking terms. The low energy spectra exhibit distinct phenomenological properties and di er from conventional schemes considered so far. (orig.)

  1. Lepton-mediated electroweak baryogenesis

    International Nuclear Information System (INIS)

    Chung, Daniel J. H.; Garbrecht, Bjorn; Ramsey-Musolf, Michael J.; Tulin, Sean

    2010-01-01

    We investigate the impact of the tau and bottom Yukawa couplings on the transport dynamics for electroweak baryogenesis in supersymmetric extensions of the standard model. Although it has generally been assumed in the literature that all Yukawa interactions except those involving the top quark are negligible, we find that the tau and bottom Yukawa interaction rates are too fast to be neglected. We identify an illustrative 'lepton-mediated electroweak baryogenesis' scenario in which the baryon asymmetry is induced mainly through the presence of a left-handed leptonic charge. We derive analytic formulas for the computation of the baryon asymmetry that, in light of these effects, are qualitatively different from those in the established literature. In this scenario, for fixed CP-violating phases, the baryon asymmetry has opposite sign compared to that calculated using established formulas.

  2. Vasoactive mediators and splanchnic perfusion.

    Science.gov (United States)

    Reilly, P M; Bulkley, G B

    1993-02-01

    To provide an overview of the splanchnic hemodynamic response to circulatory shock. Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Pertinent data were abstracted from the cited articles. The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

  3. Mediated electrochemical hazardous waste destruction

    International Nuclear Information System (INIS)

    Hickman, R.G.; Farmer, J.C.; Wang, F.T.

    1991-08-01

    There are few permitted processes for mixed waste (radioactive plus chemically hazardous) treatment. We are developing electrochemical processes that convert the toxic organic components of mixed waste to water, carbon dioxide, an innocuous anions such as chloride. Aggressive oxidizer ions such as Ag 2+ or Ce +4 are produced at an anode. These can attack the organic molecules directly. They can also attack water which yields hydroxyl free radicals that in turn attack the organic molecules. The condensed (i.e., solid and/or liquid) effluent streams contain the inorganic radionuclide forms. These may be treated with existing technology and prepared for final disposal. Kinetics and the extent of destruction of some toxic organics have been measured. Depending on how the process is operated, coulombic efficiency can be nearly 100%. In addition, hazardous organic materials are becoming very expensive to dispose of and when they are combined with transuranic radioactive elements no processes are presently permitted. Mediated electrochemical oxidation is an ambient-temperature aqueous-phase process that can be used to oxidize organic components of mixed wastes. Problems associated with incineration, such as high-temperature volatilization of radionuclides, are avoided. Historically, Ag (2) has been used as a mediator in this process. Fe(6) and Co(3) are attractive alternatives to Ag(2) since they form soluble chlorides during the destruction of chlorinated solvents. Furthermore, silver itself is a toxic heavy metal. Quantitative data has been obtained for the complete oxidation of ethylene glycol by Fe(6) and Co(3). Though ethylene glycol is a nonhalogenated organic, this data has enabled us to make direct comparisons of activities of Fe(6) and Co(3) with Ag(2). Very good quantitative data for the oxidation of ethylene glycol by Ag(2) had already been collected. 4 refs., 6 figs

  4. Designing business rules for mediation : a process towards agent-mediated business coordination

    OpenAIRE

    Zhao, Z.; Dignum, M.V.; Dignum, F.P.M.

    2008-01-01

    Business process integration is a very active research area, in which mediation is one of the fundamental architectural choices. Mediators have difficulties to design mediation services that meet the requirements of the different stakeholders. Business rules play an important role in the decision process of mediation. In this paper, we analyze the role of business rules in the decision process, and use some examples to illustrate how business rules should be designed in order to help the deci...

  5. MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

    OpenAIRE

    Fallath, Thorya; Kidd, Brendan N.; Stiller, Jiri; Davoine, Celine; Bj?rklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

    2017-01-01

    The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display do...

  6. Forms of Mediation: The Case of Interpreter-Mediated Interactions in Medical Systems

    Science.gov (United States)

    Baraldi, Claudio

    2009-01-01

    This paper analyses the forms of mediation in interlinguistic interactions performed in Italian healthcare services and in contexts of migration. The literature encourages dialogic transformative mediation, empowering participants' voices and changing cultural presuppositions in social systems. It may be doubtful, however, whether mediation can…

  7. Designing business rules for mediation : a process towards agent-mediated business coordination

    NARCIS (Netherlands)

    Zhao, Z.; Dignum, M.V.; Dignum, F.P.M.

    2008-01-01

    Business process integration is a very active research area, in which mediation is one of the fundamental architectural choices. Mediators have difficulties to design mediation services that meet the requirements of the different stakeholders. Business rules play an important role in the

  8. Factor affecting Agrobacterium -mediated transformation of rice ...

    African Journals Online (AJOL)

    Potato is a very important food crop and is adversely affected by fungus. Agrobacterium-mediated transformation can play an important role in the improvement of potato. The present study was conducted to optimize the different factors affecting Agrobacterium-mediated transformation of chitinase gene. Nodes were used as ...

  9. Regional Organisations and International Mediation: The ...

    African Journals Online (AJOL)

    Regional Organisations and International Mediation: The Effectiveness of Insider Mediators. ... During the last two decades of the twentieth century, the world witnessed an increasing number of regional conflict management efforts undertaken by regional inter-governmental organisations. There are therefore strong reasons ...

  10. Parent Mediation Empowers Sibling Conflict Resolution

    Science.gov (United States)

    Ross, Hildy S.; Lazinski, Marysia J.

    2014-01-01

    Research Findings: For the current study, formal mediation procedures were adapted for families and parents were trained and asked to mediate their children's disputes; control group parents intervened as they normally would. Conflict negotiations with parents and their children (ages 3½-11 years) occurring 3 and 7 weeks following training, and…

  11. Semiotic Mediation within an AT Frame

    Science.gov (United States)

    Maracci, Mirko; Mariotti, Maria Alessandra

    2013-01-01

    This article is meant to present a specific elaboration of the notion of mediation in relation to the use of artefacts to enhance mathematics teaching and learning: the elaboration offered by the Theory of Semiotic Mediation. In particular, it provides an explicit model--consistent with the activity-actions-operations framework--of the actions…

  12. A General Approach to Causal Mediation Analysis

    Science.gov (United States)

    Imai, Kosuke; Keele, Luke; Tingley, Dustin

    2010-01-01

    Traditionally in the social sciences, causal mediation analysis has been formulated, understood, and implemented within the framework of linear structural equation models. We argue and demonstrate that this is problematic for 3 reasons: the lack of a general definition of causal mediation effects independent of a particular statistical model, the…

  13. Integrating Mediators and Moderators in Research Design

    Science.gov (United States)

    MacKinnon, David P.

    2011-01-01

    The purpose of this article is to describe mediating variables and moderating variables and provide reasons for integrating them in outcome studies. Separate sections describe examples of moderating and mediating variables and the simplest statistical model for investigating each variable. The strengths and limitations of incorporating mediating…

  14. Elaborative Retrieval: Do Semantic Mediators Improve Memory?

    Science.gov (United States)

    Lehman, Melissa; Karpicke, Jeffrey D.

    2016-01-01

    The elaborative retrieval account of retrieval-based learning proposes that retrieval enhances retention because the retrieval process produces the generation of semantic mediators that link cues to target information. We tested 2 assumptions that form the basis of this account: that semantic mediators are more likely to be generated during…

  15. Histone modifications influence mediator interactions with chromatin

    Science.gov (United States)

    Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

    2011-01-01

    The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

  16. Mediator: A key regulator of plant development.

    Science.gov (United States)

    Buendía-Monreal, Manuel; Gillmor, C Stewart

    2016-11-01

    Mediator is a multiprotein complex that regulates transcription at the level of RNA pol II assembly, as well as through regulation of chromatin architecture, RNA processing and recruitment of epigenetic marks. Though its modular structure is conserved in eukaryotes, its subunit composition has diverged during evolution and varies in response to environmental and tissue-specific inputs, suggesting different functions for each subunit and/or Mediator conformation. In animals, Mediator has been implicated in the control of differentiation and morphogenesis through modulation of numerous signaling pathways. In plants, studies have revealed roles for Mediator in regulation of cell division, cell fate and organogenesis, as well as developmental timing and hormone responses. We begin this review with an overview of biochemical mechanisms of yeast and animal Mediator that are likely to be conserved in all eukaryotes, as well as a brief discussion of the role of Mediator in animal development. We then present a comprehensive review of studies of the role of Mediator in plant development. Finally, we point to important questions for future research on the role of Mediator as a master coordinator of development. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Understanding and Using Mediators and Moderators

    Science.gov (United States)

    Wu, Amery D.; Zumbo, Bruno D.

    2008-01-01

    Mediation and moderation are two theories for refining and understanding a causal relationship. Empirical investigation of mediators and moderators requires an integrated research design rather than the data analyses driven approach often seen in the literature. This paper described the conceptual foundation, research design, data analysis, as…

  18. A default Bayesian hypothesis test for mediation

    NARCIS (Netherlands)

    Nuijten, M.B.; Wetzels, R.; Matzke, D.; Dolan, C.V.; Wagenmakers, E.J.

    2015-01-01

    In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent

  19. Que Es la Mediacion? (What Is Mediation?).

    Science.gov (United States)

    Consortium for Appropriate Dispute Resolution in Special Education (CADRE), Eugene, OR.

    This brief paper, in Spanish, discusses the use of mediation as a method for resolving disagreements between schools or early intervention programs and parents of children with disabilities. It identifies benefits of mediation such as maintenance of an ongoing and positive relationship between the school and family, simple resolution of conflicts…

  20. Mediator-dependent Nuclear Receptor Functions

    Science.gov (United States)

    Chen, Wei; Roeder, Robert

    2011-01-01

    As gene-specific transcription factors, nuclear hormone receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Mediator has proved to be a crucial, and general, nuclear receptor-interacting coactivator, with demonstrated functions in transcription steps ranging from chromatin remodeling to subsequent PIC formation and function. Here we discuss (i) our current understanding of pathways that nuclear receptors and other interacting cofactors employ to recruit Mediator to target gene enhancers and promoters, including conditional requirements for the strong NR-Mediator interactions mediated by the NR AF2 domain and the MED1 LXXLLL motifs and (ii) mechanisms by which Mediator acts to transmit signals from enhancer-bound nuclear receptors to the general transcription machinery at core promoters to effect PIC formation and function. PMID:21854863

  1. A computational description of simple mediation analysis

    Directory of Open Access Journals (Sweden)

    Caron, Pier-Olivier

    2018-04-01

    Full Text Available Simple mediation analysis is an increasingly popular statistical analysis in psychology and in other social sciences. However, there is very few detailed account of the computations within the model. Articles are more often focusing on explaining mediation analysis conceptually rather than mathematically. Thus, the purpose of the current paper is to introduce the computational modelling within simple mediation analysis accompanied with examples with R. Firstly, mediation analysis will be described. Then, the method to simulate data in R (with standardized coefficients will be presented. Finally, the bootstrap method, the Sobel test and the Baron and Kenny test all used to evaluate mediation (i.e., indirect effect will be developed. The R code to implement the computation presented is offered as well as a script to carry a power analysis and a complete example.

  2. Elder mediation in theory and practice: study results from a national caregiver mediation demonstration project.

    Science.gov (United States)

    Crampton, Alexandra

    2013-01-01

    Mediation is a process through which a third party facilitates discussion among disputing parties to help them identify interests and ideally reach an amicable solution. Elder mediation is a growing subspecialty to address conflicts involving older adults, primarily involving caregiving or finances. Mediation is theorized to empower participants but critics argue that it can exacerbate power imbalances among parties and coerce consensus. These contested claims are examined through study of a national caregiver mediation demonstration project. Study implications underscore the importance of gerontological social work expertise to ensure the empowerment of vulnerable older adults in mediation sessions.

  3. 7 CFR 785.5 - Fees for mediation services.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Fees for mediation services. 785.5 Section 785.5... AGRICULTURE SPECIAL PROGRAMS CERTIFIED STATE MEDIATION PROGRAM § 785.5 Fees for mediation services. A requirement that non-USDA parties who elect to participate in mediation pay a fee for mediation services will...

  4. Atomic Force Microscope Mediated Chromatography

    Science.gov (United States)

    Anderson, Mark S.

    2013-01-01

    The atomic force microscope (AFM) is used to inject a sample, provide shear-driven liquid flow over a functionalized substrate, and detect separated components. This is demonstrated using lipophilic dyes and normal phase chromatography. A significant reduction in both size and separation time scales is achieved with a 25-micron-length column scale, and one-second separation times. The approach has general applications to trace chemical and microfluidic analysis. The AFM is now a common tool for ultra-microscopy and nanotechnology. It has also been demonstrated to provide a number of microfluidic functions necessary for miniaturized chromatography. These include injection of sub-femtoliter samples, fluidic switching, and sheardriven pumping. The AFM probe tip can be used to selectively remove surface layers for subsequent microchemical analysis using infrared and tip-enhanced Raman spectroscopy. With its ability to image individual atoms, the AFM is a remarkably sensitive detector that can be used to detect separated components. These diverse functional components of microfluidic manipulation have been combined in this work to demonstrate AFM mediated chromatography. AFM mediated chromatography uses channel-less, shear-driven pumping. This is demonstrated with a thin, aluminum oxide substrate and a non-polar solvent system to separate a mixture of lipophilic dyes. In conventional chromatographic terms, this is analogous to thin-layer chromatography using normal phase alumina substrate with sheardriven pumping provided by the AFM tip-cantilever mechanism. The AFM detection of separated components is accomplished by exploiting the variation in the localized friction of the separated components. The AFM tip-cantilever provides the mechanism for producing shear-induced flows and rapid pumping. Shear-driven chromatography (SDC) is a relatively new concept that overcomes the speed and miniaturization limitations of conventional liquid chromatography. SDC is based on a

  5. Immunomodulatory Effects Mediated by Dopamine

    Science.gov (United States)

    Alvarez-Herrera, Samantha; Pérez-Sánchez, Gilberto; Becerril-Villanueva, Enrique; Cruz-Fuentes, Carlos; Flores-Gutierrez, Enrique Octavio; Quintero-Fabián, Saray

    2016-01-01

    Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers. PMID:27795960

  6. Immunomodulatory Effects Mediated by Dopamine

    Directory of Open Access Journals (Sweden)

    Rodrigo Arreola

    2016-01-01

    Full Text Available Dopamine (DA, a neurotransmitter in the central nervous system (CNS, has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R and D2-like receptors (D2R, D3R, and D4R. The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS, there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

  7. Thigmotaxis Mediates Trail Odour Disruption.

    Science.gov (United States)

    Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

    2017-05-10

    Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

  8. Mediators and moderators in early intervention research.

    Science.gov (United States)

    Breitborde, Nicholas J K; Srihari, Vinod H; Pollard, Jessica M; Addington, Donald N; Woods, Scott W

    2010-05-01

    The goal of this paper is to provide clarification with regard to the nature of mediator and moderator variables and the statistical methods used to test for the existence of these variables. Particular attention will be devoted to discussing the ways in which the identification of mediator and moderator variables may help to advance the field of early intervention in psychiatry. We completed a literature review of the methodological strategies used to test for mediator and moderator variables. Although several tests for mediator variables are currently available, recent evaluations suggest that tests which directly evaluate the indirect effect are superior. With regard to moderator variables, two approaches ('pick-a-point' and regions of significance) are available, and we provide guidelines with regard to how researchers can determine which approach may be most appropriate to use for their specific study. Finally, we discuss how to evaluate the clinical importance of mediator and moderator relationships as well as the methodology to calculate statistical power for tests of mediation and moderation. Further exploration of mediator and moderator variables may provide valuable information with regard to interventions provided early in the course of a psychiatric illness.

  9. Function and regulation of the Mediator complex.

    Science.gov (United States)

    Conaway, Ronald C; Conaway, Joan Weliky

    2011-04-01

    Over the past few years, advances in biochemical and genetic studies of the structure and function of the Mediator complex have shed new light on its subunit architecture and its mechanism of action in transcription by RNA polymerase II (pol II). The development of improved methods for reconstitution of recombinant Mediator subassemblies is enabling more in-depth analyses of basic features of the mechanisms by which Mediator interacts with and controls the activity of pol II and the general initiation factors. The discovery and characterization of multiple, functionally distinct forms of Mediator characterized by the presence or absence of the Cdk8 kinase module have led to new insights into how Mediator functions in both Pol II transcription activation and repression. Finally, progress in studies of the mechanisms by which the transcriptional activation domains (ADs) of DNA binding transcription factors target Mediator have brought to light unexpected complexities in the way Mediator participates in signal transduction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Are mediation clauses binding and mandatory?

    Directory of Open Access Journals (Sweden)

    Constantinescu Miruna

    2017-06-01

    Full Text Available This study analyses the legal force of mediation clauses in the common law systems and civil law systems with a main focus on the Romanian approach. First, the introductory section illustrates the paradox between the concept of binding and mandatory effect and the mediation mechanism, a voluntary manner to settle disputes. Notwithstanding, the possibility to coerce the parties to engage into a mediation, the voluntary character of the process is illustrated by the parties’ freedom to decide whether they settle or not. Second, the role of mediation clause is analysed and its advantages are briefly described. Third, the non-compliance of the prior mediation mechanism is presented, the starting point of the discussion being represented by the manner in which the parties drafted the mediation clause. A carefully drafted mediation clause, reflecting the parties’ consent, can determine a court or an arbitral tribunal to enforce such clause. Fourth, the study ends by mentioning the approach adopted by different national courts, emphasizing the Romanian legal perspective.

  11. Mediators as the Walrasian Auctioneers of Exchange Theory

    OpenAIRE

    Dickenson, David

    2003-01-01

    This article opens up mediation to systematic economic analysis by considering mediators as analogous to the Walrasian auctioneers of exchange theory. By altering trade-off rates among bargaining issues, mediators facilitate a process leading towards Pareto efficient voluntary settlements.

  12. Energy National Mediator activity report 2009

    International Nuclear Information System (INIS)

    2009-01-01

    After some data illustrating the activity of the Energy National Mediator in 2009, and an interview of a representative of this institution who comments its practice, this report proposes the opinions of the different involved actors (communities, consumer associations, providers, and so on) about the mediator. It puts the adopted strategy in perspective from the past year to the coming one. It describes the missions: information, advice, protection. It reports actions, recommendations and facts for 2009 in terms of consumer information, group mediation, poverty management, samples of analysed disputes. It presents the social organisation and gives a financial assessment of the institution

  13. Current rectification by mediating electroactive polymers

    Energy Technology Data Exchange (ETDEWEB)

    Ybarra, Gabriel; Moina, Carlos [Centro de Investigacion sobre Electrodeposicion y Procesos Superficiales, Instituto Nacional de Tecnologia Industrial, CC 157, (1650) San Martin (Argentina); Florit, M. Ines [INIFTA, Facultad de Ciencias Exactas, UNLP, Suc. 4, CC 16, (1900) La Plata (Argentina); Posadas, Dionisio [INIFTA, Facultad de Ciencias Exactas, UNLP, Suc. 4, CC 16, (1900) La Plata (Argentina)], E-mail: dposadas@inifta.unlp.edu.ar

    2008-04-20

    In this work we briefly review the theoretical basis for the electrochemical rectification in mediated redox reactions at redox polymer modified electrodes. Electrochemical rectification may have two distinct origins. It is either caused by a slow kinetics of the reaction between the external redox couple and the mediator or it is originated by a slow electronic transport within the film under an unfavorable thermodynamic condition. We show experimental results for the redox mediation reaction of poly(o-aminophenol) (POAP) on the Fe{sup 2+/3+} and on the Fe(CN){sub 6}{sup 3-/4-} redox couples in solution that prove the proposed mechanisms of electrochemical rectification.

  14. Singlet deflected anomaly/gauge mediation

    International Nuclear Information System (INIS)

    Blas, J. de; Delgado, A.

    2012-01-01

    We study an extension of the standard anomaly/gauge mediation scenario where the messenger fields have direct interactions with an extra gauge singlet. This realizes a phenomenologically viable NMSSM-like scenario free of the μ-b μ problem. Current cosmological constraints imply a small size for the anomaly-mediation contributions, unless some source of R-parity violation is permitted. In the latter case the allowed regions in the parameter space can be substantially larger than in the corresponding gauge-mediation scenario.

  15. Current rectification by mediating electroactive polymers

    International Nuclear Information System (INIS)

    Ybarra, Gabriel; Moina, Carlos; Florit, M. Ines; Posadas, Dionisio

    2008-01-01

    In this work we briefly review the theoretical basis for the electrochemical rectification in mediated redox reactions at redox polymer modified electrodes. Electrochemical rectification may have two distinct origins. It is either caused by a slow kinetics of the reaction between the external redox couple and the mediator or it is originated by a slow electronic transport within the film under an unfavorable thermodynamic condition. We show experimental results for the redox mediation reaction of poly(o-aminophenol) (POAP) on the Fe 2+/3+ and on the Fe(CN) 6 3-/4- redox couples in solution that prove the proposed mechanisms of electrochemical rectification

  16. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  17. 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.

  18. Causal mediation analysis with multiple mediators in the presence of treatment noncompliance.

    Science.gov (United States)

    Park, Soojin; Kürüm, Esra

    2018-05-20

    Randomized experiments are often complicated because of treatment noncompliance. This challenge prevents researchers from identifying the mediated portion of the intention-to-treated (ITT) effect, which is the effect of the assigned treatment that is attributed to a mediator. One solution suggests identifying the mediated ITT effect on the basis of the average causal mediation effect among compliers when there is a single mediator. However, considering the complex nature of the mediating mechanisms, it is natural to assume that there are multiple variables that mediate through the causal path. Motivated by an empirical analysis of a data set collected in a randomized interventional study, we develop a method to estimate the mediated portion of the ITT effect when both multiple dependent mediators and treatment noncompliance exist. This enables researchers to make an informed decision on how to strengthen the intervention effect by identifying relevant mediators despite treatment noncompliance. We propose a nonparametric estimation procedure and provide a sensitivity analysis for key assumptions. We conduct a Monte Carlo simulation study to assess the finite sample performance of the proposed approach. The proposed method is illustrated by an empirical analysis of JOBS II data, in which a job training intervention was used to prevent mental health deterioration among unemployed individuals. Copyright © 2018 John Wiley & Sons, Ltd.

  19. Gene Therapy Mediated Breast Cancer Immunity

    National Research Council Canada - National Science Library

    Nesbit, Heike

    1999-01-01

    .... POE2 is produced by the cyclooxygenase (COX) mediated oxidation of arachidonic acid. The inhibition of COX activity in B7-1 expressing MDA-MB 231 cells restored the proliferative response of T cells...

  20. Dark matter prospects in deflected mirage mediation

    International Nuclear Information System (INIS)

    Holmes, Michael; Nelson, Brent D.

    2009-01-01

    The recently introduced deflected mirage mediation (DMM) model is a string-motivated paradigm in which all three of the major supersymmetry-breaking transmission mechanisms are operative. We begin a systematic exploration of the parameter space of this rich model context, paying special attention to the pattern of gaugino masses which arise. In this work we focus on the dark matter phenomenology of the DMM model as such signals are the least influenced by the model-dependent scalar masses. We find that a large portion of the parameter space in which the three mediation mechanisms have a similar effective mass scale of 1 TeV or less will be probed by future direct and indirect detection experiments. Distinguishing deflected mirage mediation from the mirage model without gauge mediation will prove difficult without collider input, though we indicate how gamma ray signals may provide an opportunity for distinguishing between the two paradigms

  1. Selecting a model of supersymmetry breaking mediation

    International Nuclear Information System (INIS)

    AbdusSalam, S. S.; Allanach, B. C.; Dolan, M. J.; Feroz, F.; Hobson, M. P.

    2009-01-01

    We study the problem of selecting between different mechanisms of supersymmetry breaking in the minimal supersymmetric standard model using current data. We evaluate the Bayesian evidence of four supersymmetry breaking scenarios: mSUGRA, mGMSB, mAMSB, and moduli mediation. The results show a strong dependence on the dark matter assumption. Using the inferred cosmological relic density as an upper bound, minimal anomaly mediation is at least moderately favored over the CMSSM. Our fits also indicate that evidence for a positive sign of the μ parameter is moderate at best. We present constraints on the anomaly and gauge mediated parameter spaces and some previously unexplored aspects of the dark matter phenomenology of the moduli mediation scenario. We use sparticle searches, indirect observables and dark matter observables in the global fit and quantify robustness with respect to prior choice. We quantify how much information is contained within each constraint.

  2. Unwrapping Court-Connected Mediation Agreements

    DEFF Research Database (Denmark)

    Adrian, Lin; Mykland, Solfrid

    2018-01-01

    Court-connected mediated agreements seem to both fulfil and fail the ideal of self-determination in mediation theory. In a study of 134 agreements from court-connected mediation, we found that the majority of agreements contain creative elements and display great variation in the provisions...... and understand them. The judicial language is well known for the drafters of the agreement but not the parties. Thus, court-connected mediation seems to fail aspects of self-determination when it comes to drafting agreements. We draw on new-institutional theory when we explore and explain this apparent...... they contain. These results indicate that the parties play an important role in crafting the substance of their agreements. However, we also found that the wording of the agreements is characterised by legal and bureaucratic language to the extent that people without legal training find it difficult to read...

  3. BRIEF CONSIDERATIONS REGARDING MEDIATION IN CRIMINAL MATTERS

    Directory of Open Access Journals (Sweden)

    LUMINITA DRAGNE

    2012-05-01

    Full Text Available Mediation is an alternative means of conflict resolution, is designed as a flexible procedure whose utility was observed in contrast to the deficiencies of the judiciary system. In the field of criminal law, mediation is part of the larger concept of the restorative justice whose aim is restoring the main victim in its rights. From this perspective, to the criminal process is intended, in principal, repairing of the victim's prejudice and, subsequently, to encourage the delinquent in taking responsibility and to acknowledge his guilt, and also to determine him to actively participate in repairing the damage caused. The ultimate goal of the process is giving back the delinquent to society and consequently, reducing the relapse. Romanian legislator has not taken this concept, and how it is regulated mediation in criminal matters is hesitant, cautious and ultimately ineffective. Specifically, in situations that will actually occur, victim-delinquent mediation will only take the form of "assisted reconciliation."

  4. Mediatized Extreme Right Activism and Discourse

    DEFF Research Database (Denmark)

    Peters, Rikke Alberg

    2015-01-01

    This paper presents a case study of the German neo-fascist network The Immortals (Die Unsterblichen) who in 2011 performed a flash-mob disseminated on YouTube for the so- called ‘Become Immortal’ campaign. The street protest was designed for and adapted to the specific characteristics of online...... activism. It is a good example of how new contentious action repertoires in which online and street activism intertwine have also spread to extreme right groups. Despite its neo-fascist and extreme right content the ‘Become Immortal’ campaign serves as an illustrative case for the study of mediated...... and mediatized activism. In order to analyse of the protest form, the visual aesthetics and the discourse of ‘The Immortals’, the paper mobilises two concepts from media and communication studies: mediation and mediatization. It will be argued that that the current transformation of the extreme right: that is...

  5. BOOKTUBERS MOVEMENT: EMERGING PRACTICES OF READING MEDIATION

    Directory of Open Access Journals (Sweden)

    Claudia Souza Teixeira

    2016-12-01

    Full Text Available This paper intents to investigate reading mediation practices develop by the booktubers, young people that use the YouTube in order to share information about books and to interact with other readers. We begin presenting some concepts related to reading and mediation activities, and then, talk about some aspects of cyberspace, the formation of virtual communities and the Booktubers phenomena. At last, as a result of a documental analysis of 100 videos posted by booktubers, we show the characteristics of these emerging mediation reading practices and the types of books that are more commented by them. We conclude that the conventional practices of reading mediation are the bases for the booktubers’ actuation, but they are adapted to the new kinds of elaboration, creation and organization enabled by the Internet.

  6. Mediated moderation or moderated mediation: relationship between length of unemployment, resilience, coping and health.

    Science.gov (United States)

    Sojo, Víctor; Guarino, Leticia

    2011-05-01

    The aim of the present research was to evaluate a model of mediated moderation vs. moderated mediation that could explain the relationship between length of unemployment, dispositional resilience, coping styles and depression and social functioning of Venezuelan unemployed individuals. Self-report measures were administered to a sample of 328 unemployed residents in Caracas, Venezuela. Results indicated that emotional coping acted as a mediator in the relationship between resilience and depression. Individuals with greater resilience used more detachment coping when unemployment was longer, while individuals with poorer resilience in the same situation used less avoidance coping. Resilience acted as a protective moderating factor between longer periods of unemployment and social functioning, a process mediated by detachment coping. Overall, results supported a mediated moderation model, with resilience as the moderating factor and coping as the mediator in the relation between stress due to the length of unemployment and well-being.

  7. From Mediatized Emotion to Digital Affect Cultures

    OpenAIRE

    Döveling, Katrin; Harju, Anu Annika; Sommer, Denise

    2018-01-01

    Research on the processes of mediatization aims to explore the mutual shaping of media and social life and how new media technologies influence and infiltrate social practices and cultural life. We extend this discussion of media’s role in transforming the everyday by including in the discussion the mediatization of emotion and discuss what we conceptualize as digital affect culture(s). We understand these as relational, contextual, globally emergent spaces in the digital environment where af...

  8. Nordic Mediation - Comparing Denmark and Finland

    DEFF Research Database (Denmark)

    Lappi-Seppälä, Tapio; Storgaard, Anette

    2015-01-01

    The Nordic Countries have a long common history in criminal policy but a closer look also indicates individual Development. the introduction of Victim Offender Mediation is one example of Nordic diversity in details.......The Nordic Countries have a long common history in criminal policy but a closer look also indicates individual Development. the introduction of Victim Offender Mediation is one example of Nordic diversity in details....

  9. Developing the conversation about workplace mediation

    OpenAIRE

    Kenny, Treasa

    2014-01-01

    This article examines some of the latest writing and research in relation to conflict in work and workplace mediation. It considers three specific issues of size and sector of organisations, the attitude of organisations to conflict and the employee relations environment in organisations. It reviews the various views in relation to fundamental aspects of mediation such as the neutral third party, voluntarism, informality and confidentiality to inform thinking as well as practitioner and acade...

  10. CONFLICT MANAGEMENT VIA SYSTEMICALLY PLANNED PEER MEDIATION

    OpenAIRE

    Evangelos C. Papakitsos; Konstantinos Karakiozis

    2016-01-01

    Conflicts and confrontations between students are a key-feature of school life. Especially in recent years, both the scientific and the educational community are particularly sensitive to bullying issues in the school context. Peer mediation (or school mediation) is an alternative way to manage conflicts at school. A critical evaluation of this practice is attempted, as well as its contribution to the formation of a positive attitude in school and to the decreasing of school-bullying incident...

  11. Efficient nonparametric estimation of causal mediation effects

    OpenAIRE

    Chan, K. C. G.; Imai, K.; Yam, S. C. P.; Zhang, Z.

    2016-01-01

    An essential goal of program evaluation and scientific research is the investigation of causal mechanisms. Over the past several decades, causal mediation analysis has been used in medical and social sciences to decompose the treatment effect into the natural direct and indirect effects. However, all of the existing mediation analysis methods rely on parametric modeling assumptions in one way or another, typically requiring researchers to specify multiple regression models involving the treat...

  12. Frequency and timing of leaders' mediation attempts

    OpenAIRE

    Demirağ, Elif Gizem; Demirag, Elif Gizem

    2015-01-01

    How do a state's political regime type and power status influence leader's mediation attempts? This study develops an explanation as a response to this question derived from the democratic peace theory which underlines the role of democratic norms in motivating state leaders to play a third party role in peace processes. Based on this approach, the expectation is that democratic country representatives are more likely to mediate especially in the early stage of their careers. In addition, I a...

  13. Gazetteer Brokering through Semantic Mediation

    Science.gov (United States)

    Hobona, G.; Bermudez, L. E.; Brackin, R.

    2013-12-01

    web technologies, including ontologies and a semantic mediator. The semantically-enhanced SPEGG allowed a client to submit a single query (e.g. ';hills') and to retrieve data from two separate gazetteers with different vocabularies (e.g. where one refers to ';summits' another refers to ';hills'). Supporting the SPEGG was a SPARQL server that held the ontologies and processed queries on them. Earth Science surveys and forecast always have a place on Earth. Being able to share the information about a place and solve inconsistencies about that place from different sources will enable geoscientists to better do their research. In the advent of mobile geo computing and location based services (LBS), brokering gazetteers will provide geoscientists with access to gazetteer services rich with information and functionality beyond that offered by current generic gazetteers.

  14. Ombuds’ corner: Consider mediation - some rules

    CERN Multimedia

    Vincent Vuillemin

    2013-01-01

    Mediation is a structured process in which an external party, called a mediator, helps participants generate and evaluate options that would allow them to reach a mutual agreement. It is an informal and confidential process.   The mediator does not have the power to impose an agreement on the parties, who should find it by themselves. However, the mediator controls the process. He arranges the meetings in agreement with the parties, and coordinates the details (concerning the speaking times, for example) and ensures that the parties respect of the rules which have been agreed on. He also favours advancing of the process towards a solution. The mediation process is centred on the search for a solution and a mutual agreement. In such a process, the mediator takes a neutral and impartial position, and does not advocate for a single party. He favours good communication between the parties, and will ensure that mutual respect is maintained and that the correct language is used during the discussi...

  15. Flavorful hybrid anomaly-gravity mediation

    International Nuclear Information System (INIS)

    Gross, Christian; Hiller, Gudrun

    2011-01-01

    We consider supersymmetric models where anomaly and gravity mediation give comparable contributions to the soft terms and discuss how this can be realized in a five-dimensional brane world. The gaugino mass pattern of anomaly mediation is preserved in such a hybrid setup. The flavorful gravity-mediated contribution cures the tachyonic slepton problem of anomaly mediation. The supersymmetric flavor puzzle is solved by alignment. We explicitly show how a working flavor-tachyon link can be realized with Abelian flavor symmetries and give the characteristic signatures of the framework, including O(1) slepton mass splittings between different generations and between doublets and singlets. This provides opportunities for same flavor dilepton edge measurements with missing energy at the Large Hadron Collider (LHC). Rare lepton decay rates could be close to their current experimental limit. Compared to pure gravity mediation, the hybrid model is advantageous because it features a heavy gravitino which can avoid the cosmological gravitino problem of gravity-mediated models combined with leptogenesis.

  16. Inside the mediation room - efficiency, voice and equity in workplace mediation

    OpenAIRE

    Saundry, R; Bennett, T; Wibberley, G

    2016-01-01

    Existing research into workplace mediation in the UK has tended to focus on managerial perceptions. Consequently, there has been a unitarist emphasis on the business case for mediation, revolving around its alleged superior efficiency properties compared to conventional rights-based procedures. This paper develops the research agenda in two respects: first, it foregrounds the experiences of participants in mediation through 25 interviews with individuals drawn from a variety of contexts. Seco...

  17. Mediating social media use : connecting parents mediation strategies and social media literacy

    OpenAIRE

    Daneels, Rowan; Vanwynsberghe, Hadewijch

    2017-01-01

    Abstract: Increasingly complex and multipurpose social media platforms require digital competences from parents and adolescents alike. While adolescents grow up with social media, parents have more difficulties with them, leading to uncertainties regarding their adolescents social media mediation. This study contributes to parental mediation research by (1) investigating whether mediation strategies defined by previous research are also relevant for social media use, and (2) exploring whether...

  18. Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

    Science.gov (United States)

    Loeys, Tom; Talloen, Wouter; Goubert, Liesbet; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2016-11-01

    It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others' pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break-up. © 2016 The British Psychological Society.

  19. 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

  20. A State Space Modeling Approach to Mediation Analysis

    Science.gov (United States)

    Gu, Fei; Preacher, Kristopher J.; Ferrer, Emilio

    2014-01-01

    Mediation is a causal process that evolves over time. Thus, a study of mediation requires data collected throughout the process. However, most applications of mediation analysis use cross-sectional rather than longitudinal data. Another implicit assumption commonly made in longitudinal designs for mediation analysis is that the same mediation…

  1. 29 CFR 1207.2 - Requests for Mediation Board action.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Requests for Mediation Board action. 1207.2 Section 1207.2 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD ESTABLISHMENT OF SPECIAL ADJUSTMENT BOARDS § 1207.2 Requests for Mediation Board action. (a) Requests for the National Mediation Board...

  2. 15 CFR 923.83 - Mediation of amendments.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Mediation of amendments. 923.83... Programs § 923.83 Mediation of amendments. (a) Section 307(h)(2) of the Act provides for mediation of... management program. Accordingly mediation is available to states or federal agencies when a serious...

  3. 15 CFR 930.115 - Termination of mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Termination of mediation. 930.115... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.115 Termination of mediation. Mediation shall terminate: (a) At any time the Federal and State agencies agree to a...

  4. Estimating and Testing Mediation Effects with Censored Data

    Science.gov (United States)

    Wang, Lijuan; Zhang, Zhiyong

    2011-01-01

    This study investigated influences of censored data on mediation analysis. Mediation effect estimates can be biased and inefficient with censoring on any one of the input, mediation, and output variables. A Bayesian Tobit approach was introduced to estimate and test mediation effects with censored data. Simulation results showed that the Bayesian…

  5. Surveying Parental Mediation: Connections, Challenges and Questions for Media Literacy

    Science.gov (United States)

    Mendoza, Kelly

    2009-01-01

    This paper examines three strategies of parental mediation--coviewing, restrictive mediation, and active mediation--in order to make connections, challenge, and raise questions for media literacy. Coviewing, whether it is intentional practice, or whether it functions to promote media literacy, is explored. Restrictive mediation, how it connects to…

  6. Integrating mediation and moderation to advance theory development and testing.

    Science.gov (United States)

    Karazsia, Bryan T; Berlin, Kristoffer S; Armstrong, Bridget; Janicke, David M; Darling, Katherine E

    2014-03-01

    The concepts and associated analyses of mediation and moderation are important to the field of psychology. Although pediatric psychologists frequently incorporate mediation and moderation in their theories and empirical research, on few occasions have we integrated mediation and moderation. In this article, conceptual reasons for integrating mediation and moderation are offered. We illustrate a model that integrates mediation and moderation. In our illustration, the strength of an indirect or a mediating effect varied as a function of a moderating variable. Clinical implications of the integration of mediation and moderation are discussed, as is the potential of integrated models to advance research programs in pediatric psychology.

  7. Guidelines for the Investigation of Mediating Variables in Business Research.

    Science.gov (United States)

    MacKinnon, David P; Coxe, Stefany; Baraldi, Amanda N

    2012-03-01

    Business theories often specify the mediating mechanisms by which a predictor variable affects an outcome variable. In the last 30 years, investigations of mediating processes have become more widespread with corresponding developments in statistical methods to conduct these tests. The purpose of this article is to provide guidelines for mediation studies by focusing on decisions made prior to the research study that affect the clarity of conclusions from a mediation study, the statistical models for mediation analysis, and methods to improve interpretation of mediation results after the research study. Throughout this article, the importance of a program of experimental and observational research for investigating mediating mechanisms is emphasized.

  8. In the Name of Mediation: An empirical inquiry into the Chinese court mediation practices

    NARCIS (Netherlands)

    Li, Yedan

    2015-01-01

    The statistics on the numbers of cases handled through mediation in Chinese courts show remarkable ups and downs. A strong downturn before 2004 was followed by a sharp upturn in the years 2004-2011. The return of mediation has drawn the attention of various scholars who provide different readings of

  9. Search for SUSY in gauge mediated and anomaly mediated supersymmetry breaking models

    International Nuclear Information System (INIS)

    Nunnnemann, Thomas

    2004-01-01

    In this note, recent results on the search for Gauge Mediated Supersymmetry Breaking (GMSB) and Anomaly Mediated Supersymmetry Breaking (AMSB) at the LEP and Tevatron colliders are summarized. We report on DOe's search for GMSB in di-photon events with large missing transverse energy and discuss the sensitivity of similar searches based on future Tevatron integrated luminosities. (orig.)

  10. An exponential decay model for mediation.

    Science.gov (United States)

    Fritz, Matthew S

    2014-10-01

    Mediation analysis is often used to investigate mechanisms of change in prevention research. Results finding mediation are strengthened when longitudinal data are used because of the need for temporal precedence. Current longitudinal mediation models have focused mainly on linear change, but many variables in prevention change nonlinearly across time. The most common solution to nonlinearity is to add a quadratic term to the linear model, but this can lead to the use of the quadratic function to explain all nonlinearity, regardless of theory and the characteristics of the variables in the model. The current study describes the problems that arise when quadratic functions are used to describe all nonlinearity and how the use of nonlinear functions, such as exponential decay, address many of these problems. In addition, nonlinear models provide several advantages over polynomial models including usefulness of parameters, parsimony, and generalizability. The effects of using nonlinear functions for mediation analysis are then discussed and a nonlinear growth curve model for mediation is presented. An empirical example using data from a randomized intervention study is then provided to illustrate the estimation and interpretation of the model. Implications, limitations, and future directions are also discussed.

  11. Light mediators in dark matter direct detections

    International Nuclear Information System (INIS)

    Li, Tai; Miao, Sen; Zhou, Yu-Feng

    2015-01-01

    In an extended effective operator framework, we investigate in detail the effects of light mediators on the event spectra of dark matter (DM)-nucleus scatterings. The presence of light mediators changes the interpretation of the current experimental data, especially the determination of DM particle mass. We show by analytic and numerical illustrations that in general for all the operators relevant to spin-independent scatterings, the DM particle mass allowed by a given set of experimental data increases significantly when the mediator particle becomes lighter. For instance, in the case of CDMS-II-Si experiment, the allowed DM particle mass can reach ∼50 (100) GeV at 68% (90%) confidence level, which is much larger than ∼10 GeV in the case with contact interactions. The increase of DM particle mass saturates when the mediator mass is below O(10) MeV. The upper limits from other experiments such as SuperCDMS, CDMSlite, CDEX, XENON10/100, LUX, PandaX etc. all tend to be weaker toward high DM mass regions. In a combined analysis, we show that the presence of light mediators can partially relax the tension in the current results of CDMS-II-Si, SuperCDMS and LUX

  12. A default Bayesian hypothesis test for mediation.

    Science.gov (United States)

    Nuijten, Michèle B; Wetzels, Ruud; Matzke, Dora; Dolan, Conor V; Wagenmakers, Eric-Jan

    2015-03-01

    In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g., consumption of fruits and vegetables). Almost all mediation analyses in psychology use frequentist estimation and hypothesis-testing techniques. A recent exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who outlined a Bayesian parameter estimation procedure for mediation analysis. Here we complete the Bayesian alternative to frequentist mediation analysis by specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow approach. We further extend this default Bayesian test by allowing a comparison to directional or one-sided alternatives, using Markov chain Monte Carlo techniques implemented in JAGS. All Bayesian tests are implemented in the R package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014).

  13. The Mediator Complex and Lipid Metabolism.

    Science.gov (United States)

    Zhang, Yi; Xiaoli; Zhao, Xiaoping; Yang, Fajun

    2013-03-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.

  14. 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.

  15. MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana

    Science.gov (United States)

    Stiller, Jiri; Davoine, Celine; Björklund, Stefan; Manners, John M.; Kazan, Kemal; Schenk, Peer M.

    2017-01-01

    The conserved protein complex known as Mediator conveys transcriptional signals by acting as an intermediary between transcription factors and RNA polymerase II. As a result, Mediator subunits play multiple roles in regulating developmental as well as abiotic and biotic stress pathways. In this report we identify the head domain subunits MEDIATOR18 and MEDIATOR20 as important susceptibility factors for Fusarium oxysporum infection in Arabidopsis thaliana. Mutants of MED18 and MED20 display down-regulation of genes associated with jasmonate signaling and biosynthesis while up-regulation of salicylic acid associated pathogenesis related genes and reactive oxygen producing and scavenging genes. We propose that MED18 and MED20 form a sub-domain within Mediator that controls the balance of salicylic acid and jasmonate associated defense pathways. PMID:28441405

  16. Surmounting elusive barriers: the case for bioethics mediation.

    Science.gov (United States)

    Bergman, Edward J

    2013-01-01

    This article describes, analyzes, and advocates for management of clinical healthcare conflict by a process commonly referred to as bioethics mediation. Section I provides a brief introduction to classical mediation outside the realm of clinical healthcare. Section II highlights certain distinguishing characteristics of bioethics mediation. Section III chronicles the history of bioethics mediation and references a number of seminal writings on the subject. Finally, Section IV analyzes barriers that have, thus far, limited the widespread implementation of bioethics mediation.

  17. 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.

  18. LEGAL AND INSTITUTIONAL FRAMEWORK OF MEDIATION IN REPUBLIC OF MACEDONIA

    Directory of Open Access Journals (Sweden)

    Andon Majhoshev

    2014-10-01

    Full Text Available Mediation as an alternative dispute resolution enables faster, more efficient and less costly resolution of disputes in relation to the proceedings. Its operation is based on the following principles: voluntary, equality of the parties, neutrality of the mediator, exclusion of the public, efficiency of the procedure, confidentiality of information, fairness. In Macedonia the mediation as an alternative dispute resolution was introduced by the Law on Mediation in 2006. However, besides this law, the resolution of disputes by mediation is regulated by other special laws such as the Family Law Act, Consumer Law, the Juvenile Justice, Law for the peaceful resolution of labor disputes, etc.. For effective functioning of the mediation, except legal regulation of mediation, and established appropriate institutional framework is an important link for a successful mediation. The institutional framework of mediation includes: Ministry of Justice - Sector for Mediation, Board for Mediation, the Mediators Chamber of Macedonia and mediator. All the above institutions have proper function in the system of mediation and their jurisdiction is governed normative-legal. The legal and institutional framework actually consists of mediation system in the country and represent a whole.

  19. Considerations about mediative in initial petition

    Directory of Open Access Journals (Sweden)

    Maria das Vitórias Nunes Silva Lourenço

    2013-12-01

    Full Text Available This paper presents considerations about Initial Petition, textual/discursive genre, which is a genre circumscribed in the judicial domain with relation to the Commitment. For this purpose, this article exposes the text plan of the Initial Petition from the postulations of Adam (2011. In the same way, it studies the mediative frameworks based on Guentchéva (1994, 1996, which develop the notion of mediative grammatical categories, that permits the linguistic marking of distance and engagement of the enunciator with regard to the information expressed. It evidences the relevance of the use of mediated constructions in the judicial text, as they function as attenuated strategies to the responsibility of the producer of the text with what is said, and at the same time points to a discourse of authority through the entrance of the sources of law.

  20. U(1) mediation of flux supersymmetry breaking

    Science.gov (United States)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-10-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with Script N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kähler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

  1. Revisiting R-invariant direct gauge mediation

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Cheng-Wei [Center for Mathematics and Theoretical Physics andDepartment of Physics, National Central University,Taoyuan, Taiwan 32001, R.O.C. (China); Institute of Physics, Academia Sinica,Taipei, Taiwan 11529, R.O.C. (China); Physics Division, National Center for Theoretical Sciences,Hsinchu, Taiwan 30013, R.O.C. (China); Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); Harigaya, Keisuke [Department of Physics, University of California,Berkeley, California 94720 (United States); Theoretical Physics Group, Lawrence Berkeley National Laboratory,Berkeley, California 94720 (United States); ICRR, University of Tokyo,Kashiwa, Chiba 277-8582 (Japan); Ibe, Masahiro [Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); ICRR, University of Tokyo,Kashiwa, Chiba 277-8582 (Japan); Yanagida, Tsutomu T. [Kavli IPMU (WPI), UTIAS, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan)

    2016-03-21

    We revisit a special model of gauge mediated supersymmetry breaking, the “R-invariant direct gauge mediation.” We pay particular attention to whether the model is consistent with the minimal model of the μ-term, i.e., a simple mass term of the Higgs doublets in the superpotential. Although the incompatibility is highlighted in view of the current experimental constraints on the superparticle masses and the observed Higgs boson mass, the minimal μ-term can be consistent with the R-invariant gauge mediation model via a careful choice of model parameters. We derive an upper limit on the gluino mass from the observed Higgs boson mass. We also discuss whether the model can explain the 3σ excess of the Z+jets+E{sub T}{sup miss} events reported by the ATLAS collaboration.

  2. Sensemaking in Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2006-01-01

    of advanced CSCW technologies is basically a problem of sensemaking. We analyze how a group of “technology-use mediators” (Orlikowski et al. Org. Sci. (1995) 6(4), 423) in a large, multinational company adapted a groupware 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. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology...... will be established and used in an organization. However, we also find that the process of technology-use mediation is much more complex and indeterminate than prior research suggests. The reason being, we argue, that new, advanced CSCW technologies, such as “virtual workspaces” and other groupware applications...

  3. U(1) mediation of flux supersymmetry breaking

    International Nuclear Information System (INIS)

    Grimm, Thomas W.; Klemm, Albrecht

    2008-01-01

    We study the mediation of supersymmetry breaking triggered by background fluxes in Type II string compactifications with N = 1 supersymmetry. The mediation arises due to an U(1) vector multiplet coupling to both a hidden supersymmetry breaking flux sector and a visible D-brane sector. The required internal manifolds can be constructed by non-Kaehler resolutions of singular Calabi-Yau manifolds. The effective action encoding the U(1) coupling is then determined in terms of the global topological properties of the internal space. We investigate suitable local geometries for the hidden and visible sector in detail. This includes a systematic study of orientifold symmetries of del Pezzo surfaces realized in compact geometries after geometric transition. We construct compact examples admitting the key properties to realize flux supersymmetry breaking and U(1) mediation. Their toric realization allows us to analyze the geometry of curve classes and confirm the topological connection between the hidden and visible sector.

  4. Gravity mediated supersymmetry breaking in six dimensions

    International Nuclear Information System (INIS)

    Falkowski, A.; Lee, H.M.; Luedeling, C.

    2005-04-01

    We study gravity mediated supersymmetry breaking in four-dimensional effective theories derived from six-dimensional brane-world supergravities. Using the Noether method we construct a locally supersymmetric action for a bulk-brane system consisting of the minimal six-dimensional supergravity coupled to vector and chiral multiplets located at four-dimensional branes. We compactify this system on T 2 /Z 2 and derive the four-dimensional effective supergravity. Most interestingly, sequestering of the matter living on different branes is not explicit in the tree-level Kaehler potential (but of course the action obtained from this Kaehler potential is consistent with higher dimensional locality). As a consequence, the features of gravity mediation are different than in five-dimensional models. We identify one scenario of moduli stabilization that yields positive gravity mediated soft scalar masses squared. (orig.)

  5. Mediator kinase module and human tumorigenesis.

    Science.gov (United States)

    Clark, Alison D; Oldenbroek, Marieke; Boyer, Thomas G

    2015-01-01

    Mediator is a conserved multi-subunit signal processor through which regulatory informatiosn conveyed by gene-specific transcription factors is transduced to RNA Polymerase II (Pol II). In humans, MED13, MED12, CDK8 and Cyclin C (CycC) comprise a four-subunit "kinase" module that exists in variable association with a 26-subunit Mediator core. Genetic and biochemical studies have established the Mediator kinase module as a major ingress of developmental and oncogenic signaling through Mediator, and much of its function in signal-dependent gene regulation derives from its resident CDK8 kinase activity. For example, CDK8-targeted substrate phosphorylation impacts transcription factor half-life, Pol II activity and chromatin chemistry and functional status. Recent structural and biochemical studies have revealed a precise network of physical and functional subunit interactions required for proper kinase module activity. Accordingly, pathologic change in this activity through altered expression or mutation of constituent kinase module subunits can have profound consequences for altered signaling and tumor formation. Herein, we review the structural organization, biological function and oncogenic potential of the Mediator kinase module. We focus principally on tumor-associated alterations in kinase module subunits for which mechanistic relationships as opposed to strictly correlative associations are established. These considerations point to an emerging picture of the Mediator kinase module as an oncogenic unit, one in which pathogenic activation/deactivation through component change drives tumor formation through perturbation of signal-dependent gene regulation. It follows that therapeutic strategies to combat CDK8-driven tumors will involve targeted modulation of CDK8 activity or pharmacologic manipulation of dysregulated CDK8-dependent signaling pathways.

  6. 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....

  7. Barley Transformation Using Agrobacterium-Mediated Techniques

    Science.gov (United States)

    Harwood, Wendy A.; Bartlett, Joanne G.; Alves, Silvia C.; Perry, Matthew; Smedley, Mark A.; Leyland, Nicola; Snape, John W.

    Methods for the transformation of barley using Agrobacterium-mediated techniques have been available for the past 10 years. Agrobacterium offers a number of advantages over biolistic-mediated techniques in terms of efficiency and the quality of the transformed plants produced. This chapter describes a simple system for the transformation of barley based on the infection of immature embryos with Agrobacterium tumefaciens followed by the selection of transgenic tissue on media containing the antibiotic hygromycin. The method can lead to the production of large numbers of fertile, independent transgenic lines. It is therefore ideal for studies of gene function in a cereal crop system.

  8. Auxin-dependent compositional change in Mediator in ARF7- and ARF19-mediated transcription.

    Science.gov (United States)

    Ito, Jun; Fukaki, Hidehiro; Onoda, Makoto; Li, Lin; Li, Chuanyou; Tasaka, Masao; Furutani, Masahiko

    2016-06-07

    Mediator is a multiprotein complex that integrates the signals from transcription factors binding to the promoter and transmits them to achieve gene transcription. The subunits of Mediator complex reside in four modules: the head, middle, tail, and dissociable CDK8 kinase module (CKM). The head, middle, and tail modules form the core Mediator complex, and the association of CKM can modify the function of Mediator in transcription. Here, we show genetic and biochemical evidence that CKM-associated Mediator transmits auxin-dependent transcriptional repression in lateral root (LR) formation. The AUXIN/INDOLE 3-ACETIC ACID 14 (Aux/IAA14) transcriptional repressor inhibits the transcriptional activity of its binding partners AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 by making a complex with the CKM-associated Mediator. In addition, TOPLESS (TPL), a transcriptional corepressor, forms a bridge between IAA14 and the CKM component MED13 through the physical interaction. ChIP assays show that auxin induces the dissociation of MED13 but not the tail module component MED25 from the ARF7 binding region upstream of its target gene. These findings indicate that auxin-induced degradation of IAA14 changes the module composition of Mediator interacting with ARF7 and ARF19 in the upstream region of their target genes involved in LR formation. We suggest that this regulation leads to a quick switch of signal transmission from ARFs to target gene expression in response to auxin.

  9. A classical regression framework for mediation analysis: fitting one model to estimate mediation effects.

    Science.gov (United States)

    Saunders, Christina T; Blume, Jeffrey D

    2017-10-26

    Mediation analysis explores the degree to which an exposure's effect on an outcome is diverted through a mediating variable. We describe a classical regression framework for conducting mediation analyses in which estimates of causal mediation effects and their variance are obtained from the fit of a single regression model. The vector of changes in exposure pathway coefficients, which we named the essential mediation components (EMCs), is used to estimate standard causal mediation effects. Because these effects are often simple functions of the EMCs, an analytical expression for their model-based variance follows directly. Given this formula, it is instructive to revisit the performance of routinely used variance approximations (e.g., delta method and resampling methods). Requiring the fit of only one model reduces the computation time required for complex mediation analyses and permits the use of a rich suite of regression tools that are not easily implemented on a system of three equations, as would be required in the Baron-Kenny framework. Using data from the BRAIN-ICU study, we provide examples to illustrate the advantages of this framework and compare it with the existing approaches. © The Author 2017. Published by Oxford University Press.

  10. Establishment of an efficient Agrobacterium tumefaciens -mediated ...

    African Journals Online (AJOL)

    Spine gourd (Momordica dioica Roxb. ex Willd) is a medicinally and economically important plant and also used as vegetable. In this study, we established an Agrobacterium tumefaciens-mediated transformation procedure for M. dioica. Leaf explants were incubated with A. tumefaciens strain LBA4404 containing a binary ...

  11. Mediators of mucosal inflammation : Implications for therapy

    NARCIS (Netherlands)

    VanDullemen, H; Meenan, J; Stronkhorst, A; Tytgat, GNJ; VanDenenter, SJH

    1997-01-01

    Treatment of inflammatory bowel disease remains a challenge. The major shortcoming in the development of new therapeutic approaches is the fact that the cause of inflammatory bowel disease is still unknown. Recognition of the importance of the arachidonic acid cascade of inflammatory mediators

  12. Eicosanoid-mediated immunity in insects

    Science.gov (United States)

    Eicosanoid is a collective term for oxygenated metabolites of C20 polyunsaturated fatty acids. As seen in mammals, eicosanoids play crucial roles in mediating various physiological processes, including immune responses, in insects. Upon microbial pathogen infection, non-self recognition signals are ...

  13. Regional Organisations and International Mediation: The ...

    African Journals Online (AJOL)

    Angela

    increasing number of regional conflict management efforts undertaken by ... to study the advantages and disadvantages of mediation efforts by regional ... Elgström is Professor at the Department of Political Science, Lund University,. Sweden. .... partial or full settlement) in 42.1 per cent of cases; the UN achieved success.

  14. Mediating Artifact in Teacher Professional Development

    Science.gov (United States)

    Svendsen, Bodil

    2015-01-01

    This article focuses on teacher professional development (TPD) in natural science through the 5E model as mediating artifact. The study was conducted in an upper secondary school, grounded in a school-based intervention research project. My contribution to the field of research on TPD is founded on the hypothesis that teachers would be best…

  15. Nutritionally Mediated Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Alexandra Muñoz

    2013-01-01

    Full Text Available There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

  16. Comments: Causal Interpretations of Mediation Effects

    Science.gov (United States)

    Jo, Booil; Stuart, Elizabeth A.

    2012-01-01

    The authors thank Dr. Lindsay Page for providing a nice illustration of the use of the principal stratification framework to define causal effects, and a Bayesian model for effect estimation. They hope that her well-written article will help expose education researchers to these concepts and methods, and move the field of mediation analysis in…

  17. Microbial ecology of bacterially mediated PCB biodegradation

    International Nuclear Information System (INIS)

    Pettigrew, C.A. Jr.

    1989-01-01

    The roles of plasmid mediated and consortia mediated polychlorinated biphenyl (PCB) biodegradation by bacterial populations isolated from PCB contaminated freshwater sediments were investigated. PCB degrading bacteria were isolated by DNA:DNA colony hybridization, batch enrichments, and chemostat enrichment. Analysis of substrate removal and metabolite production were done using chlorinated biphenyl spray plates, reverse phase high pressure liquid chromatography, Cl - detection, and 14 C-labeled substrate mineralization methods. A bacterial consortium, designated LPS10, involved in a concerted metabolic attack on chlorinated biphenyls, was shown to mineralize 4-chlorobiphenyl (4CB) and 4,4'-dichlorobiphenyl (4,4' CB). The LPS10 consortium was isolated by both batch and chemostat enrichment using 4CB and biphenyl (BP) as sole carbon source and was found to have tree bacterial isolates that predominated; these included: Pseudomonas, testosteroni LPS10A which mediated the breakdown of 4CB and 4,4' CB to the putative meta-cleavage product and subsequently to 4-chlorobenzoic acid (4CBA), an isolate tentatively identified as an Arthrobacter sp. LPS10B which mediated 4CBA degradation, and Pseudomonas putida by A LPS10C whose role in the consortium has not been determined

  18. Design research into mobile museum mediation

    DEFF Research Database (Denmark)

    Baggesen, Rikke Haller

    2013-01-01

    community. 
The PhD research project “Mobile Mediation of Fashion by Museums” explores how aesthetic and ethnographic design methods can be used to develop mobile experiences and articulate museological matters of concern. Building on user perspectives, expressed in response to cultural probes, the project...

  19. Teaching Task Sequencing via Verbal Mediation.

    Science.gov (United States)

    Rusch, Frank R.; And Others

    1987-01-01

    Verbal sequence training was used to teach a moderately mentally retarded woman to sequence job-related tasks. Learning to say the tasks in the proper sequence resulted in the employee performing her tasks in that sequence, and the employee was capable of mediating her own work behavior when scheduled changes occurred. (Author/JDD)

  20. Genetic transformation of Physcomitrella patens mediated by ...

    African Journals Online (AJOL)

    USER

    2010-06-21

    Jun 21, 2010 ... plants could be obtained after 4 generations of selective culture. PCR analysis showed that gene ... 5'-triphosphate; SDS, sodium dodecyl sulfate; YFP, your favorite protein. ..... affected the transformation rate mediated by Agro- bacterium, this was confirmed and the result showed only the gametophores ...

  1. Analyzing the mediated voice - a datasession

    DEFF Research Database (Denmark)

    Lawaetz, Anna

    Broadcasted voices are technologically manipulated. In order to achieve a certain autencity or sound of “reality” paradoxically the voices are filtered and trained in order to reach the listeners. This “mis-en-scene” is important knowledge when it comes to the development of a consistent method o...... of analysis of the mediated voice...

  2. RETHINKING RESEARCH ETHICS FOR MEDIATED SETTINGS

    NARCIS (Netherlands)

    Beaulieu, Anne; Estalella, Adolfo

    2012-01-01

    An important feature of e-research is the increased mediation of research practices, which changes not only the objects and tools of research, but also the relation between researcher and object, between researchers, and between researchers and their constituencies and stakeholders. This article

  3. Optimization of Agrobacterium -mediated transformation parameters ...

    African Journals Online (AJOL)

    Agrobacterium-mediated transformation factors for sweet potato embryogenic calli were optimized using -glucuronidase (GUS) as a reporter. The binary vector pTCK303 harboring the modified GUS gene driven by the CaMV 35S promoter was used. Transformation parameters were optimized including bacterial ...

  4. Improving Undergraduates' Critique via Computer Mediated Communication

    Science.gov (United States)

    Mohamad, Maslawati; Musa, Faridah; Amin, Maryam Mohamed; Mufti, Norlaila; Latiff, Rozmel Abdul; Sallihuddin, Nani Rahayu

    2014-01-01

    Our current university students, labeled as "Generation Y" or Millennials, are different from previous generations due to wide exposure to media. Being technologically savvy, they are accustomed to Internet for information and social media for socializing. In line with this current trend, teaching through computer mediated communication…

  5. Detergent-Mediated Reconstitution of Membrane Proteins

    NARCIS (Netherlands)

    Knol, J; Sjollema, K.A; Poolman, B.

    1998-01-01

    The efficiency of reconstitution of the lactose transport protein (LacS) of Streptococcus thermophilus is markedly higher with Triton X-100 than with other detergents commonly employed to mediate the membrane insertion. To rationalize these differences, the lipid/detergent structures that are formed

  6. The Role of Artefacts in Presence Mediation

    NARCIS (Netherlands)

    Vyas, Dhaval; Tzovaras, D

    2007-01-01

    Approaches to support computer mediated communication (CMC) have predominantly relied on the face-to-face communication paradigm. However, interaction and coordination can also be supported by different technological artefacts. In fact, most researches [1, 2, 3] related to ethnomethodology have

  7. Proteinaceous molecules mediating Bifidobacterium-host interactions

    Directory of Open Access Journals (Sweden)

    Lorena Ruiz

    2016-08-01

    Full Text Available Bifidobacteria are commensal microoganisms found in the gastrointestinal tract.Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs.

  8. Mediation Analyses in the Real World

    DEFF Research Database (Denmark)

    Lange, Theis; Starkopf, Liis

    2016-01-01

    The paper by Nguyen et al.1 published in this issue of Epidemiology presents a comparison of the recently suggested inverse odds ratio approach for addressing mediation and a more conventional Baron and Kenny-inspired method. Interestingly, the comparison is not done through a discussion of restr......The paper by Nguyen et al.1 published in this issue of Epidemiology presents a comparison of the recently suggested inverse odds ratio approach for addressing mediation and a more conventional Baron and Kenny-inspired method. Interestingly, the comparison is not done through a discussion...... it simultaneously ensures that the comparison is based on properties, which matter in actual applications, and makes the comparison accessible for a broader audience. In a wider context, the choice to stay close to real-life problems mirrors a general trend within the literature on mediation analysis namely to put...... applications using the inverse odds ration approach, as it simply has not had enough time to move from theoretical concept to published applied paper, we do expect to be able to judge the willingness of authors and journals to employ the causal inference-based approach to mediation analyses. Our hope...

  9. Sonication assisted Agrobacterium -mediated transformation of ...

    African Journals Online (AJOL)

    In this study, a protocol was developed to obtain stable lines of the Spring Dendrobium cultivar 'Sanya' via sonication assisted Agrobacterium-mediated transformation (SAAT) of protocorm-like bodies (PLBs). Agrobacterium tumefaciens strain LBA4404 was used with the binary vector AG205 containing the chalcone ...

  10.  Fashion Mediators and Distributed Agency

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    intermediaries" (Bourdieu, 1984) which designates a certain class of people. Empirically, the paper works with the cultural and aesthetic economies - and with fashion in particular. Using the mediator as central concept, the paper presents empirical stories from the field of fashion, and fashion marketing...

  11. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and

  12. Identification as a Mediator of Celebrity Effects.

    Science.gov (United States)

    Basil, Michael D.

    1996-01-01

    This study examined personal concern, perceived risk, and sexual behavior of 147 college students a year after Magic Johnson announced he tested positive for HIV (Human Immunodeficiency Virus). It found that identification mediates message effects, suggesting that a spokesperson with whom an audience can identify insures the greatest likelihood of…

  13. Characterization of BASP1-mediated neurite outgrowth

    DEFF Research Database (Denmark)

    Korshunova, Irina; Caroni, Pico; Kolkova, Kateryna

    2008-01-01

    The brain acid-soluble protein BASP1 (CAP-23, NAP-22) belongs to the family of growth-associated proteins, which also includes GAP-43, a protein recently shown to regulate neural cell adhesion molecule (NCAM)-mediated neurite outgrowth. Here, the effects of BASP1 overexpression were investigated...

  14. Volatile-mediated interactions in the rhizosphere

    NARCIS (Netherlands)

    Cordovez da Cunha, Viviane

    2016-01-01

    Plants and microorganisms are constantly engaged in highly dynamic interactions both above- and belowground. Several of these interactions are mediated by volatile organic compounds (VOCs), small carbon-based compounds with high vapor pressure at ambient temperature. In the rhizosphere, VOCs have

  15. A Comparison of Three Tests of Mediation

    Science.gov (United States)

    Warbasse, Rosalia E.

    2009-01-01

    A simulation study was conducted to evaluate the performance of three tests of mediation: the bias-corrected and accelerated bootstrap (Efron & Tibshirani, 1993), the asymmetric confidence limits test (MacKinnon, 2008), and a multiple regression approach described by Kenny, Kashy, and Bolger (1998). The evolution of these methods is reviewed and…

  16. Structure of Energetic Particle Mediated Shocks Revisited

    International Nuclear Information System (INIS)

    Mostafavi, P.; Zank, G. P.; Webb, G. M.

    2017-01-01

    The structure of collisionless shock waves is often modified by the presence of energetic particles that are not equilibrated with the thermal plasma (such as pickup ions [PUIs] and solar energetic particles [SEPs]). This is relevant to the inner and outer heliosphere and the Very Local Interstellar Medium (VLISM), where observations of shock waves (e.g., in the inner heliosphere) show that both the magnetic field and thermal gas pressure are less than the energetic particle component pressures. Voyager 2 observations revealed that the heliospheric termination shock (HTS) is very broad and mediated by energetic particles. PUIs and SEPs contribute both a collisionless heat flux and a higher-order viscosity. We show that the incorporation of both effects can completely determine the structure of collisionless shocks mediated by energetic ions. Since the reduced form of the PUI-mediated plasma model is structurally identical to the classical cosmic ray two-fluid model, we note that the presence of viscosity, at least formally, eliminates the need for a gas sub-shock in the classical two-fluid model, including in that regime where three are possible. By considering parameters upstream of the HTS, we show that the thermal gas remains relatively cold and the shock is mediated by PUIs. We determine the structure of the weak interstellar shock observed by Voyager 1 . We consider the inclusion of the thermal heat flux and viscosity to address the most general form of an energetic particle-thermal plasma two-fluid model.

  17. Cultural Mediators Seduced by Mad Men:

    DEFF Research Database (Denmark)

    Kristensen, Nete Nørgaard; Hellman, Heikki; Riegert, Kristina

    2017-01-01

    Based on theories about the role of cultural mediators in cultural production and using the TV series Mad Men as a case, this article investigates how cultural journalists in the Nordic countries have contributed to legitimizing “quality TV series” as a worthy field of aesthetic consumption. Key...

  18. Holographic gauge mediation via strongly coupled messengers

    International Nuclear Information System (INIS)

    McGuirk, Paul; Shiu, Gary; Sumitomo, Yoske

    2010-01-01

    We consider a relative of semidirect gauge mediation where the hidden sector exists at large 't Hooft coupling. Such scenarios can be difficult to describe using perturbative field theory methods but may fall into the class of holographic gauge mediation scenarios, meaning that they are amenable to the techniques of gauge/gravity duality. We use a recently found gravity solution to examine one such case, where the hidden sector is a cascading gauge theory resulting in a confinement scale not much smaller than the messenger mass. In the original construction of holographic gauge mediation, as in other examples of semidirect gauge mediation at strong coupling, the primary contributions to visible sector soft terms come from weakly coupled messenger mesons. In contrast to these examples, we describe the dual of a gauge theory where there are significant contributions from scales in which the strongly coupled messenger quarks are the effective degrees of freedom. In this regime, the visible sector gaugino mass can be calculated entirely from holography.

  19. [Children in family mediation: A practice model].

    Science.gov (United States)

    Mayer, Stefan; Normann, Katrin

    2006-01-01

    The authors briefly describe the history of family mediation under the perspective of the role of the children in the process of mediation. They state that originally children were not directly included. But through empirical studies and different higher escalated families asking for help by mediation, the inclusion of children got an important issue in theory and practice. The discussion began with the question in which phases of the mediation process the children should be included - it went to the issue of the age of the children - and the authors propose to take the amount of escalation in the family as the most important point of reference to decide if and how the children should be included. They suggest to diagnose the loss of responsibility and autonomy of the parents on a nine level scale (from F. Glasl) with the parents and to decide and negotiate with them how the children will be included. They describe five different settings of inclusion of the children.

  20. Mitogen-activated protein kinases mediate Mycobacterium ...

    Indian Academy of Sciences (India)

    2012-01-19

    Jan 19, 2012 ... CD44, an adhesion molecule, has been reported to be a binding site for ... receptors in mediating mitogen-activated protein kinase activation. ... surface expression and tumour necrosis factor-alpha levels, ... Abbreviations used: Abs, antibodies; ANOVA, analysis of variance; AP-1, activator protein -1; BCG, ...

  1. 7 CFR 205.663 - Mediation.

    Science.gov (United States)

    2010-01-01

    ..., Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) ORGANIC FOODS PRODUCTION ACT PROVISIONS NATIONAL ORGANIC PROGRAM Administrative Compliance § 205.663 Mediation. Any dispute with respect to denial of certification or proposed suspension or revocation of certification under this part may...

  2. Mitogen-activated protein kinases mediate Mycobacterium

    Indian Academy of Sciences (India)

    CD44, an adhesion molecule, has been reported to be a binding site for Mycobacterium tuberculosis (M. tuberculosis) in macrophages and it also mediates mycobacterial phagocytosis, macrophage recruitment and protective immunity against pulmonary tuberculosis in vivo. However, the signalling pathways that are ...

  3. Synchronous Computer-Mediated Communication and Interaction

    Science.gov (United States)

    Ziegler, Nicole

    2016-01-01

    The current study reports on a meta-analysis of the relative effectiveness of interaction in synchronous computer-mediated communication (SCMC) and face-to-face (FTF) contexts. The primary studies included in the analysis were journal articles and dissertations completed between 1990 and 2012 (k = 14). Results demonstrate that interaction in SCMC…

  4. Integrating Computer-Mediated Communication Strategy Instruction

    Science.gov (United States)

    McNeil, Levi

    2016-01-01

    Communication strategies (CSs) play important roles in resolving problematic second language interaction and facilitating language learning. While studies in face-to-face contexts demonstrate the benefits of communication strategy instruction (CSI), there have been few attempts to integrate computer-mediated communication and CSI. The study…

  5. Structure of Energetic Particle Mediated Shocks Revisited

    Energy Technology Data Exchange (ETDEWEB)

    Mostafavi, P.; Zank, G. P. [Department of Space Science, University of Alabama in Huntsville, Huntsville, AL 35899 (United States); Webb, G. M. [Center for Space Plasma and Aeronomic Research (CSPAR), University of Alabama in Huntsville, Huntsville, AL 35899 (United States)

    2017-05-20

    The structure of collisionless shock waves is often modified by the presence of energetic particles that are not equilibrated with the thermal plasma (such as pickup ions [PUIs] and solar energetic particles [SEPs]). This is relevant to the inner and outer heliosphere and the Very Local Interstellar Medium (VLISM), where observations of shock waves (e.g., in the inner heliosphere) show that both the magnetic field and thermal gas pressure are less than the energetic particle component pressures. Voyager 2 observations revealed that the heliospheric termination shock (HTS) is very broad and mediated by energetic particles. PUIs and SEPs contribute both a collisionless heat flux and a higher-order viscosity. We show that the incorporation of both effects can completely determine the structure of collisionless shocks mediated by energetic ions. Since the reduced form of the PUI-mediated plasma model is structurally identical to the classical cosmic ray two-fluid model, we note that the presence of viscosity, at least formally, eliminates the need for a gas sub-shock in the classical two-fluid model, including in that regime where three are possible. By considering parameters upstream of the HTS, we show that the thermal gas remains relatively cold and the shock is mediated by PUIs. We determine the structure of the weak interstellar shock observed by Voyager 1 . We consider the inclusion of the thermal heat flux and viscosity to address the most general form of an energetic particle-thermal plasma two-fluid model.

  6. Strategic Game Moves Mediate Implicit Science Learning

    Science.gov (United States)

    Rowe, Elizabeth; Baker, Ryan S.; Asbell-Clarke, Jodi

    2015-01-01

    Educational games have the potential to be innovative forms of learning assessment, by allowing us to not just study their knowledge but the process that takes students to that knowledge. This paper examines the mediating role of players' moves in digital games on changes in their pre-post classroom measures of implicit science learning. We…

  7. Processes mediating expertise in air traffic control

    NARCIS (Netherlands)

    Van Meeuwen, Ludo; Jarodzka, Halszka; Brand-Gruwel, Saskia; Van Merriënboer, Jeroen; De Bock, Jeano; Kirschner, Paul A.

    2010-01-01

    Van Meeuwen, L., Jarodzka, H., Brand-Gruwel, S., Van Merriënboer, J. J. G., De Bock, J. J. P. R., & Kirschner, P. A. (2010, August). Processes mediating expertise in air traffic control. Meeting of the EARLI SIG6/7 Instructional Design and Learning and Instruction with Computers, Ulm, Germany.

  8. 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

  9. Teaching Responsibly with Technology-Mediated Communication

    Science.gov (United States)

    Veltsos, Jennifer R.; Veltsos, Christophe

    2010-01-01

    Technology-mediated communication, or "new media," such as blogs, Twitter, wikis, and social network sites, can be an endless source of ideas for activities or inspiration for classroom discussion. Many instructors ask students to monitor current events by following keywords and industry leaders on Twitter and reading both corporate and…

  10. Bridging the Divide: Cross-Cultural Mediation

    Science.gov (United States)

    Mahan, Laura N.; Mahuna, Joshua M.

    2017-01-01

    The article strives to contribute to the growing field of conflict resolution by analyzing contrasting cross-cultural perceptions through insights from multiple areas to resolve intercultural conflicts and disputes. Western-centric mediation techniques are dissected in juxtaposition to indigenous methodologies in degrees of (1) substantiality and…

  11. Cooperative learning, problem solving and mediating artifacts

    African Journals Online (AJOL)

    PROF.MIREKU

    10, 2012. 39. Cooperative learning, problem solving and mediating artifacts. F. Bahmaei6 & N. ... out cooperative learning in the end, post-test was done and by analyzing the tests it was concluded that ... Johnson et al, 1991 b, Reynolds et al. 1995, Vidakovic .... connection of mental constructs (Hiebert, Carpenter, 1992).

  12. Processes mediating expertise in air traffic control

    NARCIS (Netherlands)

    Van Meeuwen, Ludo; Jarodzka, Halszka; Brand-Gruwel, Saskia; Van Merriënboer, Jeroen; De Bock, Jeano; Kirschner, Paul A.

    2011-01-01

    Van Meeuwen, L. W., Jarodzka, H., Brand-Gruwel, S., Van Merriënboer, J. J. G., De Bock, J. J. P. R., & Kirschner, P. A. (2010, September). Processes mediating expertise in air traffic control. Poster presented at the European Association for Aviation Psychology Conference, Budapest.

  13. Web-Mediated Knowledge Synthesis for Educators

    Science.gov (United States)

    DeSchryver, Michael

    2015-01-01

    Ubiquitous and instant access to information on the Web is challenging what constitutes 21st century literacies. This article explores the notion of Web-mediated knowledge synthesis, an approach to integrating Web-based learning that may result in generative synthesis of ideas. This article describes the skills and strategies that may support…

  14. Associated technologies ensures complete loop mediated ...

    African Journals Online (AJOL)

    Loop Mediated Isothermal Amplification (LAMP) assay could be a useful adjunct diagnostic assay along with the conventional methods that would preclude the requirement of continuous maintenance of pure cultures. Moreover, LAMP assay is simple, rapid, specific and sensitive for the detection of pathogens. Having ...

  15. THE SCIENCE OF COMMUNICATION AND NEGOTIATION IN MEDIATION

    Directory of Open Access Journals (Sweden)

    ELENA NEDELCU

    2011-04-01

    Full Text Available The present study proposes to contribute in clarifying a subject of great actuality and social importance: why does the contemporary society need such mediation and mediators and what are the psycho-social premises of making the process of mediaton more efficient. In the first part, this study keeps the track of identifying the connections and the distinctions between communication-negotiation and mediation. The intercession carries forward with the analysis of the communicational and negotiative abilities of the mediator – premises of efficient mediation. The final part consists in an argument towards the imperative need of mediation felt by the contemporary society at all its levels.

  16. On the Interpretation and Use of Mediation: Multiple Perspectives on Mediation Analysis.

    Science.gov (United States)

    Agler, Robert; De Boeck, Paul

    2017-01-01

    Mediation analysis has become a very popular approach in psychology, and it is one that is associated with multiple perspectives that are often at odds, often implicitly. Explicitly discussing these perspectives and their motivations, advantages, and disadvantages can help to provide clarity to conversations and research regarding the use and refinement of mediation models. We discuss five such pairs of perspectives on mediation analysis, their associated advantages and disadvantages, and their implications: with vs. without a mediation hypothesis, specific effects vs. a global model, directness vs. indirectness of causation, effect size vs. null hypothesis testing, and hypothesized vs. alternative explanations. Discussion of the perspectives is facilitated by a small simulation study. Some philosophical and linguistic considerations are briefly discussed, as well as some other perspectives we do not develop here.

  17. On the Interpretation and Use of Mediation: Multiple Perspectives on Mediation Analysis

    Science.gov (United States)

    Agler, Robert; De Boeck, Paul

    2017-01-01

    Mediation analysis has become a very popular approach in psychology, and it is one that is associated with multiple perspectives that are often at odds, often implicitly. Explicitly discussing these perspectives and their motivations, advantages, and disadvantages can help to provide clarity to conversations and research regarding the use and refinement of mediation models. We discuss five such pairs of perspectives on mediation analysis, their associated advantages and disadvantages, and their implications: with vs. without a mediation hypothesis, specific effects vs. a global model, directness vs. indirectness of causation, effect size vs. null hypothesis testing, and hypothesized vs. alternative explanations. Discussion of the perspectives is facilitated by a small simulation study. Some philosophical and linguistic considerations are briefly discussed, as well as some other perspectives we do not develop here. PMID:29187828

  18. Reconstitution of DNA strand exchange mediated by Rhp51 recombinase and two mediators.

    Directory of Open Access Journals (Sweden)

    Yumiko Kurokawa

    2008-04-01

    Full Text Available In the fission yeast Schizosaccharomyces pombe, genetic evidence suggests that two mediators, Rad22 (the S. pombe Rad52 homolog and the Swi5-Sfr1 complex, participate in a common pathway of Rhp51 (the S. pombe Rad51 homolog-mediated homologous recombination (HR and HR repair. Here, we have demonstrated an in vitro reconstitution of the central step of DNA strand exchange during HR. Our system consists entirely of homogeneously purified proteins, including Rhp51, the two mediators, and replication protein A (RPA, which reflects genetic requirements in vivo. Using this system, we present the first robust biochemical evidence that concerted action of the two mediators directs the loading of Rhp51 onto single-stranded DNA (ssDNA precoated with RPA. Dissection of the reaction reveals that Rad22 overcomes the inhibitory effect of RPA on Rhp51-Swi5-Sfr1-mediated strand exchange. In addition, Rad22 negates the requirement for a strict order of protein addition to the in vitro system. However, despite the presence of Rad22, Swi5-Sfr1 is still essential for strand exchange. Importantly, Rhp51, but neither Rad22 nor the Swi5-Sfr1 mediator, is the factor that displaces RPA from ssDNA. Swi5-Sfr1 stabilizes Rhp51-ssDNA filaments in an ATP-dependent manner, and this stabilization is correlated with activation of Rhp51 for the strand exchange reaction. Rad22 alone cannot activate the Rhp51 presynaptic filament. AMP-PNP, a nonhydrolyzable ATP analog, induces a similar stabilization of Rhp51, but this stabilization is independent of Swi5-Sfr1. However, hydrolysis of ATP is required for processive strand transfer, which results in the formation of a long heteroduplex. Our in vitro reconstitution system has revealed that the two mediators have indispensable, but distinct, roles for mediating Rhp51 loading onto RPA-precoated ssDNA.

  19. Developing models of how cognitive improvements change functioning: Mediation, moderation and moderated mediation

    Science.gov (United States)

    Wykes, Til; Reeder, Clare; Huddy, Vyv; Taylor, Rumina; Wood, Helen; Ghirasim, Natalia; Kontis, Dimitrios; Landau, Sabine

    2012-01-01

    Background Cognitive remediation (CRT) affects functioning but the extent and type of cognitive improvements necessary are unknown. Aim To develop and test models of how cognitive improvement transfers to work behaviour using the data from a current service. Method Participants (N49) with a support worker and a paid or voluntary job were offered CRT in a Phase 2 single group design with three assessments: baseline, post therapy and follow-up. Working memory, cognitive flexibility, planning and work outcomes were assessed. Results Three models were tested (mediation — cognitive improvements drive functioning improvement; moderation — post treatment cognitive level affects the impact of CRT on functioning; moderated mediation — cognition drives functioning improvements only after a certain level is achieved). There was evidence of mediation (planning improvement associated with improved work quality). There was no evidence that cognitive flexibility (total Wisconsin Card Sorting Test errors) and working memory (Wechsler Adult Intelligence Scale III digit span) mediated work functioning despite significant effects. There was some evidence of moderated mediation for planning improvement if participants had poorer memory and/or made fewer WCST errors. The total CRT effect on work quality was d = 0.55, but the indirect (planning-mediated CRT effect) was d = 0.082 Conclusion Planning improvements led to better work quality but only accounted for a small proportion of the total effect on work outcome. Other specific and non-specific effects of CRT and the work programme are likely to account for some of the remaining effect. This is the first time complex models have been tested and future Phase 3 studies need to further test mediation and moderated mediation models. PMID:22503640

  20. Practical Guidance for Conducting Mediation Analysis With Multiple Mediators Using Inverse Odds Ratio Weighting

    OpenAIRE

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

    2015-01-01

    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 be...

  1. Mediated electrochemical oxidation of organic wastes using a Co(III) mediator in a neutral electrolyte

    International Nuclear Information System (INIS)

    Balazs, G.B.; Lewis, P.R.

    1999-01-01

    An electrochemical cell with a Co(III) mediator and neutral pH anolyte provides efficient destruction of organic and mixed wastes. The organic waste is concentrated in the anolyte reservoir, where the cobalt mediator oxidizes the organics and insoluble radioactive species and is regenerated at the anode until all organics are converted to carbon dioxide and destroyed. The neutral electrolyte is non-corrosive, and thus extends the lifetime of the cell and its components. 2 figs

  2. Phenomenology of flavor-mediated supersymmetry breaking

    International Nuclear Information System (INIS)

    Kaplan, D. Elazzar; Kribs, Graham D.

    2000-01-01

    The phenomenology of a new economical supersymmetric model that utilizes dynamical supersymmetry breaking and gauge mediation for the generation of the sparticle spectrum and the hierarchy of fermion masses is discussed. Similarities between the communication of supersymmetry breaking through a messenger sector and the generation of flavor using the Froggatt-Nielsen (FN) mechanism are exploited, leading to the identification of vector-like messenger fields with FN fields and the messenger U(1) as a flavor symmetry. An immediate consequence is that the first and second generation scalars acquire flavor-dependent masses, but do not violate flavor changing neutral current bounds since their mass scale, consistent with ''effective supersymmetry,'' is of order 10 TeV. We define and advocate a ''minimal flavor-mediated model'' (MFMM), recently introduced in the literature, which successfully accommodates the small flavor-breaking parameters of the standard model using order 1 couplings and ratios of flavon field VEVs. The mediation of supersymmetry breaking occurs via two-loop logarithm-enhanced gauge-mediated contributions, as well as several one-loop and two-loop Yukawa-mediated contributions for which we provide analytical expressions. The MFMM is parametrized by a small set of masses and couplings, with values restricted by several model constraints and experimental data. Full two-loop renormalization group evolution is performed, correctly taking into account the negative two-loop gauge contributions from heavy first and second generations. Electroweak symmetry is radiatively broken with the value of μ determined by matching to the Z mass. The weak scale spectrum is generally rather heavy, except for the lightest Higgs boson, the lightest stau, the lightest chargino, the lightest two neutralinos, and of course a very light gravitino. The next-to-lightest sparticle always has a decay length that is larger than the scale of a detector, and is either the lightest stau

  3. Best (but oft-forgotten) practices: mediation analysis12

    Science.gov (United States)

    McDaniel, Heather L

    2017-01-01

    This contribution in the “Best (but Oft-Forgotten) Practices” series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. PMID:28446497

  4. Best (but oft-forgotten) practices: mediation analysis.

    Science.gov (United States)

    Fairchild, Amanda J; McDaniel, Heather L

    2017-06-01

    This contribution in the "Best (but Oft-Forgotten) Practices" series considers mediation analysis. A mediator (sometimes referred to as an intermediate variable, surrogate endpoint, or intermediate endpoint) is a third variable that explains how or why ≥2 other variables relate in a putative causal pathway. The current article discusses mediation analysis with the ultimate intention of helping nutrition researchers to clarify the rationale for examining mediation, avoid common pitfalls when using the model, and conduct well-informed analyses that can contribute to improving causal inference in evaluations of underlying mechanisms of effects on nutrition-related behavioral and health outcomes. We give specific attention to underevaluated limitations inherent in common approaches to mediation. In addition, we discuss how to conduct a power analysis for mediation models and offer an applied example to demonstrate mediation analysis. Finally, we provide an example write-up of mediation analysis results as a model for applied researchers. © 2017 American Society for Nutrition.

  5. Human-mediated drivers of change — impacts on coastal ...

    African Journals Online (AJOL)

    Human-mediated drivers of change — impacts on coastal ecosystems and marine ... of global change because they are located at the land–ocean interface and ... upwelling regimes are all being affected by human-mediated climate change.

  6. Biologically mediated dissolution of volcanic glass in seawater

    NARCIS (Netherlands)

    Staudigel, H; Yayanos, A; Chastain, R; Davies, G.T.; Verdurmen, E.A Th; Schiffmann, P; Bourcier, R; de Baar, H.J.W.

    1998-01-01

    We studied the effects of biological mediation on the dissolution of basaltic glass in seawater. Experiments with typical seawater microbial populations were contrasted with a sterile control, and reactions were monitored chemically and isotopically. Biologically mediated experiments produce twice

  7. Non-IgE-mediated food allergies | Terblanche | South African ...

    African Journals Online (AJOL)

    mediated conditions such as atopic dermatitis and eosinophilic oesophagitis, and pure T-cell-mediated conditions such as food protein-induced enterocolitis syndrome, allergic proctocolitis and enteropathy syndromes. Diagnosing mixed or ...

  8. Guidelines for the Investigation of Mediating Variables in Business Research

    OpenAIRE

    MacKinnon, David P.; Coxe, Stefany; Baraldi, Amanda N.

    2011-01-01

    Business theories often specify the mediating mechanisms by which a predictor variable affects an outcome variable. In the last 30 years, investigations of mediating processes have become more widespread with corresponding developments in statistical methods to conduct these tests. The purpose of this article is to provide guidelines for mediation studies by focusing on decisions made prior to the research study that affect the clarity of conclusions from a mediation study, the statistical mo...

  9. Conceptualising International Peace Mediation - Bring Back the Law

    OpenAIRE

    Higgins, Noelle; Daly, Brenda

    2011-01-01

    Mediation has been acknowledged and utilised for a number of decades as an effective method of alternative dispute resolution in a variety of areas of law, including family law, commercial law and medical law. A uniform, standardised framework exists within legal discourse which clearly identifies and categorises three main styles of mediation as facilitative, evaluative and transformative mediation. In the post-Cold War period, mediation has also emerged as an important resolution tool in ar...

  10. 25-Hydroxyvitamin D and Peripheral Immune Mediators

    DEFF Research Database (Denmark)

    Thorsen, Steffen; Pipper, Christian; Skogstrand, Kristin

    2017-01-01

    Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470...... patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981–1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997–2005. A variety of peripheral immune mediators were measured and compared...... to total 25(OH)D levels (25(OH)D2 + 25(OH)D3). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH...

  11. Lignin Biodegradation with Laccase-Mediator Systems

    International Nuclear Information System (INIS)

    Christopher, Lew Paul; Yao, Bin; Ji, Yun

    2014-01-01

    Lignin has a significant and largely unrealized potential as a source for the sustainable production of fuels and bulk high-value chemicals. It can replace fossil-based oil as a renewable feedstock that would bring about socio-economic and environmental benefits in our transition to a biobased economy. The efficient utilization of lignin however requires its depolymerization to low-molecular weight phenolics and aromatics that can then serve as the building blocks for chemical syntheses of high-value products. The ability of laccase to attack and degrade lignin in conjunction with laccase mediators is currently viewed as one of the potential “breakthrough” applications for lignin valorization. Here, we review the recent progress in lignin biodegradation with laccase-mediator systems, and research needs that need to be addressed in this field.

  12. Gravity-mediated (or Composite) Dark Matter

    CERN Document Server

    Lee, Hyun Min; Sanz, Veronica

    2014-01-01

    Dark matter could have an electroweak origin, yet communicate with the visible sector exclusively through gravitational interactions. In a set-up addressing the hierarchy problem, we propose a new dark matter scenario where gravitational mediators, arising from the compactification of extra-dimensions, are responsible for dark matter interactions and its relic abundance in the Universe. We write an explicit example of this mechanism in warped extra-dimensions and work out its constraints. We also develop a dual picture of the model, based on a four-dimensional scenario with partial compositeness. We show that Gravity-mediated Dark Matter is equivalent to a mechanism of generating viable dark matter scenarios in a strongly-coupled, near-conformal theory, such as in composite Higgs models.

  13. 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.

  14. The Maieutic Force of Mediating Instruments

    DEFF Research Database (Denmark)

    Revellino, Silvana; Mouritsen, Jan

    and coordinating complex investments in inter-organizational spaces, the paper explores the role of the Chronoprogram in managing compromises and directing attention to concerns in relation to the development of an Italian piece of motorway(the Variante di Valico).The Chronoprogram acts as a mediating instrument......This paper investigates how compromising plays a role when framing, developing and appraising capital budgeting projects. Motivated by Miller & O’Leary’s (1997, 2005a, 2005b, 2007) call for further research on capital budgeting to include not only valuation practices but also practices for managing...... which leads multiple and dispersed actors to compromising on the investment project. In these compromising spaces, which enable questioning to emerge, disagreements and controversies are temporarily appeased even in the absence of an interest alignment. The mediating properties of the Chronoprogram...

  15. Gravity mediated supersymmetry breaking in six dimensions

    International Nuclear Information System (INIS)

    Falkowski, Adam; Lee, Hyun Min; Luedeling, Christoph

    2005-01-01

    We study gravity mediated supersymmetry breaking in four-dimensional effective theories derived from six-dimensional brane-world supergravity. Using the Noether method we construct a locally supersymmetric action for a bulk-brane system consisting of the minimal six-dimensional supergravity coupled to vector and chiral multiplets located at four-dimensional branes. Couplings of the bulk moduli to the brane are uniquely fixed, in particular, they are flavour universal. We compactify this system on T 2 /Z 2 and derive the four-dimensional effective supergravity. The tree-level effective Kaehler potential is not of the sequestered form, therefore gravity mediation may occur at tree-level. We identify one scenario of moduli stabilization in which the soft scalar masses squared are positive

  16. Supersymmetry Breaking, Gauge Mediation, and the LHC

    International Nuclear Information System (INIS)

    Shih, David

    2015-01-01

    Gauge mediated SUSY breaking (GMSB) is a promising class of supersymmetric models that automatically satisfies the precision constraints. Prior work of Meade, Seiberg and Shih in 2008 established the full, model-independent parameter space of GMSB, which they called 'General Gauge Mediation' (GGM). During the first half of 2010-2015, Shih and his collaborators thoroughly explored the parameter space of GGM and established many well-motivated benchmark models for use by the experimentalists at the LHC. Through their work, the current constraints on GGM from LEP, the Tevatron and the LHC were fully elucidated, together with the possible collider signatures of GMSB at the LHC. This ensured that the full discovery potential for GGM could be completely realized at the LHC.

  17. Emotion regulation mediates age differences in emotions.

    Science.gov (United States)

    Yeung, Dannii Y; Wong, Carmen K M; Lok, David P P

    2011-04-01

    This study aimed at testing the proposition of socioemotional selectivity theory whether older people would use more antecedent-focused emotion regulatory strategies like cognitive reappraisal but fewer response-focused strategies like suppression. It also aimed at investigating the mediating role of emotion regulation on the relationship between age and emotions. The sample consisted of 654 younger and older adults aged between 18 and 64. Results showed that age was significantly associated with positive emotions and cognitive reappraisal. No difference was found in negative emotions and suppression between younger and older adults. Cognitive reappraisal partially mediated the effect of age on positive emotions. Findings of this study contribute to our understanding of the underlying mechanism of age variations in emotional experiences.

  18. Lignin Biodegradation with Laccase-Mediator Systems

    Energy Technology Data Exchange (ETDEWEB)

    Christopher, Lew Paul, E-mail: lew.christopher@sdsmt.edu [Center for Bioprocessing Research and Development, South Dakota School of Mines & Technology, Rapid City, SD (United States); Department of Civil and Environmental Engineering, South Dakota School of Mines & Technology, Rapid City, SD (United States); Yao, Bin [Center for Bioprocessing Research and Development, South Dakota School of Mines & Technology, Rapid City, SD (United States); Ji, Yun [Department of Chemical Engineering, University of North Dakota, Grand Forks, ND (United States)

    2014-03-31

    Lignin has a significant and largely unrealized potential as a source for the sustainable production of fuels and bulk high-value chemicals. It can replace fossil-based oil as a renewable feedstock that would bring about socio-economic and environmental benefits in our transition to a biobased economy. The efficient utilization of lignin however requires its depolymerization to low-molecular weight phenolics and aromatics that can then serve as the building blocks for chemical syntheses of high-value products. The ability of laccase to attack and degrade lignin in conjunction with laccase mediators is currently viewed as one of the potential “breakthrough” applications for lignin valorization. Here, we review the recent progress in lignin biodegradation with laccase-mediator systems, and research needs that need to be addressed in this field.

  19. 29 CFR 1202.2 - Interpretation of mediation agreements.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Interpretation of mediation agreements. 1202.2 Section 1202.2 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.2 Interpretation of mediation agreements. Under section 5, Second, of title I of the Railway Labor...

  20. 15 CFR 930.114 - Secretarial mediation efforts.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Secretarial mediation efforts. 930.114... MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.114 Secretarial mediation efforts. (a) Following the close of the hearing, the hearing officer shall transmit the...

  1. 45 CFR 400.83 - Mediation and fair hearings.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Mediation and fair hearings. 400.83 Section 400.83... Employment § 400.83 Mediation and fair hearings. (a) Mediation—(1) Public/private RCA program. The State must ensure that a mediation period prior to imposition of sanctions is provided to refugees by local...

  2. 7 CFR 900.103 - Application for mediation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Application for mediation. 900.103 Section 900.103 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Application for mediation. An application for mediation by a cooperative, shall be in writing and shall...

  3. 76 FR 19310 - Information Collection; Certified State Mediation Program

    Science.gov (United States)

    2011-04-07

    ... DEPARTMENT OF AGRICULTURE Farm Service Agency Information Collection; Certified State Mediation... supports the Certified State Mediation Program. The information collection is necessary to ensure the grant... submit comments by any of the following methods: Mail: Carol Wagner, Certified State Mediation Program...

  4. Meaningful mediation analysis : Plausible causal inference and informative communication

    NARCIS (Netherlands)

    Pieters, Rik

    2017-01-01

    Statistical mediation analysis has become the technique of choice in consumer research to make causal inferences about the influence of a treatment on an outcome via one or more mediators. This tutorial aims to strengthen two weak links that impede statistical mediation analysis from reaching its

  5. 15 CFR 930.112 - Request for Secretarial mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Request for Secretarial mediation. 930... RESOURCE MANAGEMENT FEDERAL CONSISTENCY WITH APPROVED COASTAL MANAGEMENT PROGRAMS Secretarial Mediation § 930.112 Request for Secretarial mediation. (a) The Secretary or other head of a Federal agency, or the...

  6. 40 CFR 7.180 - Mediation of age discrimination complaints.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Mediation of age discrimination... Discrimination Prohibited on the Basis of Age § 7.180 Mediation of age discrimination complaints. (a) The OCR will refer all accepted complaints alleging age discrimination to the Mediation Agency designated by...

  7. 29 CFR 1203.3 - Interpretation of mediation agreements.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Interpretation of mediation agreements. 1203.3 Section 1203.3 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD APPLICATIONS FOR SERVICE § 1203.3 Interpretation of mediation agreements. (a) Applications may be filed with the Board's Chief of...

  8. The Use of Propensity Scores in Mediation Analysis

    Science.gov (United States)

    Jo, Booil; Stuart, Elizabeth A.; MacKinnon, David P.; Vinokur, Amiram D.

    2011-01-01

    Mediation analysis uses measures of hypothesized mediating variables to test theory for how a treatment achieves effects on outcomes and to improve subsequent treatments by identifying the most efficient treatment components. Most current mediation analysis methods rely on untested distributional and functional form assumptions for valid…

  9. Modelling User Preferences and Mediating Agents in Electronic Commerce

    NARCIS (Netherlands)

    Dastani, M.M.; Jacobs, N.; Jonker, C.M.; Treur, J.

    2005-01-01

    An important ingredient in agent-mediated electronic commerce is the presence of intelligent mediating agents that assist electronic commerce participants (e.g. individual users, other agents, organisations). These mediating agents are in principle autonomous agents that interact with their

  10. Modeling User Preferences and Mediating Agents in Electronic Commerce

    NARCIS (Netherlands)

    Dastani, M.M.; Jacobs, N.; Jonker, C.M.; Treur, J.; Dignum, F.; Sierra, C.

    2001-01-01

    An important ingredient in agent-mediated Electronic Commerce is the presence of intelligent mediating agents that assist Electronic Commerce participants (e.g., individual users, other agents, organisations). These mediating agents are in principle autonomous agents that will interact with their

  11. 7 CFR 900.106 - Assignment of mediator.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Assignment of mediator. 900.106 Section 900.106 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Assignment of mediator. The Director of the Division shall assign a mediator, from the group designated by...

  12. Murine Colitis is Mediated by Vimentin

    OpenAIRE

    Mor-Vaknin, Nirit; Legendre, Maureen; Yu, Yue; Serezani, Carlos H. C.; Garg, Sanjay K.; Jatzek, Anna; Swanson, Michael D.; Gonzalez-Hernandez, Marta J.; Teitz-Tennenbaum, Seagal; Punturieri, Antonello; Engleberg, N. Cary; Banerjee, Ruma; Peters-Golden, Marc; Kao, John Y.; Markovitz, David M.

    2013-01-01

    Vimentin, an abundant intermediate filament protein, presumably has an important role in stabilizing intracellular architecture, but its function is otherwise poorly understood. In a vimentin knockout (Vim KO) mouse model, we note that Vim KO mice challenged with intraperitoneal Escherichia coli control bacterial infection better than do wild-type (WT) mice. In vitro, Vim KO phagocytes show significantly increased capacity to mediate bacterial killing by abundant production of reactive oxygen...

  13. The New Flavor of Higgsed Gauge Mediation

    OpenAIRE

    Craig, Nathaniel; McCullough, Matthew; Thaler, Jesse

    2012-01-01

    Recent LHC bounds on squark masses combined with naturalness and flavor considerations motivate non-trivial sfermion mass spectra in the supersymmetric Standard Model. These can arise if supersymmetry breaking is communicated to the visible sector via new extended gauge symmetries. Such extended symmetries must be spontaneously broken, or confined, complicating the calculation of soft masses. We develop a new formalism for calculating perturbative gauge-mediated two-loop soft masses for gauge...

  14. Strain mediated interaction of adatom dimers

    OpenAIRE

    Kappus, Wolfgang

    2013-01-01

    An earlier model for substrate strain mediated interactions between monomer adatoms is extended to the interaction of monomers with dimers and the interaction of dimers. While monomers (sitting on high symmetric sites) are supposed to create isotropic stress on the substrate, dimers would create anisotropic stress caused by stretching their bond. Resulting interactions are strongly angle dependent and also reflect the elastic anisotropy of the substrate. The applicability of a continuum elast...

  15. Leptonic Dark Matter with Scalar Dilepton Mediator

    OpenAIRE

    Ma, Ernest

    2018-01-01

    A simple and elegant mechanism is proposed to resolve the problem of having a light scalar mediator for self-interacting dark matter and the resulting disruption to the cosmic microwave background (CMB) at late times by the former's enhanced Sommerfeld production and decay. The crucial idea is to have Dirac neutrinos with the conservation of U(1) lepton number extended to the dark sector. The simplest scenario consists of scalar or fermion dark matter with unit lepton number accompanied by a ...

  16. Agrobacterium-mediated transformation of lipomyces

    Science.gov (United States)

    Dai, Ziyu; Magnuson, Jon K.; Deng, Shuang; Bruno, Kenneth S.; Culley, David E.

    2018-03-13

    This disclosure provides Agrobacterium-mediated transformation methods for the oil-producing (oleaginous) yeast Lipomyces sp., as well as yeast produced by the method. Such methods utilize Agrobacterium sp. cells that have a T-DNA binary plasmid, wherein the T-DNA binary plasmid comprises a first nucleic acid molecule encoding a first protein and a second nucleic acid molecule encoding a selective marker that permits growth of transformed Lipomyces sp. cells in selective culture media comprising an antibiotic.

  17. Tear Mediators in Corneal Ectatic Disorders.

    Directory of Open Access Journals (Sweden)

    Dorottya Pásztor

    Full Text Available To compare the concentrations of 11 tear mediators in order to reveal the biochemical difference between pellucid marginal degeneration (PMD and keratoconus (KC.We have designed a cross-sectional study in which patients with corneal ectasia based on slit-lamp biomicroscopy and Pentacam HR (keratometry values (K1, K2, Kmax, astigmatism, minimal radius of curvature (Rmin, corneal thickness (Apex and Min, indices (surface variation, vertical asymmetry, keratoconus, central keratoconus, height asymmetry and decentration were enrolled. Eyes of keratoconic patients were similar to the PMD patients in age and severity (K2, Kmax and Rmin. Non-stimulated tear samples were collected from nine eyes of seven PMD patients, 55 eyes of 55 KC patients and 24 eyes of 24 healthy controls. The mediators' (interleukin -6, -10, chemokine ligand 5, -8, -10, matrix metalloproteinase (MMP -9, -13, tissue inhibitor of metalloproteinases (TIMP-1, tissue plasminogen activator, plasminogen activator inhibitor, nerve growth factor concentrations were measured using Cytometric Bead Array.MMP-9 was the only mediator which presented relevant variances between the two patient groups (p = 0.005. The ratios of MMP-9 and TIMP-1 were 2.45, 0.40 and 0.23 in PMD, KC and the controls, respectively.As far as we are aware, this is the first study that aims to reveal the biochemical differences between PMD and KC. Further studies of biomarkers to investigate the precise role of these mediators need to be defined, and it is important to confirm the observed changes in a larger study to gain further insights into the molecular alterations in PMD.

  18. Instrumentness for Creativity - Mediation, Materiality & Metonymy

    DEFF Research Database (Denmark)

    Bertelsen, Olav Wedege; Breinbjerg, Morten; Pold, Søren

    2007-01-01

    in use beyond what is initially designed for. The paper performs a conceptual investigation into qualities in software interfaces that support creativity, supported by analysis of, and interviews with, musical composers. Instrumentness is explained through discussions of materiality and metonymy...... as central strategies for computer mediated creativity. The paper is contributing to an investigation of the aesthetics of use in relation to software, pointing to alternative values, differing from traditional usability, which are also relevant in creative work outside art and music composition....

  19. Modelling Toehold-Mediated RNA Strand Displacement

    OpenAIRE

    Šulc, Petr; Ouldridge, Thomas E.; Romano, Flavio; Doye, Jonathan P.K.; Louis, Ard A.

    2015-01-01

    We study the thermodynamics and kinetics of an RNA toehold-mediated strand displacement reaction with a recently developed coarse-grained model of RNA. Strand displacement, during which a single strand displaces a different strand previously bound to a complementary substrate strand, is an essential mechanism in active nucleic acid nanotechnology and has also been hypothesized to occur in vivo. We study the rate of displacement reactions as a function of the length of the toehold and temperat...

  20. The Mediator Complex and Lipid Metabolism

    OpenAIRE

    Zhang, Yi; Xiaoli,; Zhao, Xiaoping; Yang, Fajun

    2013-01-01

    The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understan...

  1. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

    2010-01-01

    a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  2. Lithium-mediated protection against ethanol neurotoxicity

    Directory of Open Access Journals (Sweden)

    Jia Luo

    2010-06-01

    Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

  3. Data Mediation with Enterprise Level Security

    Directory of Open Access Journals (Sweden)

    Kevin E. Foltz

    2017-10-01

    Full Text Available Enterprise Level Security (ELS is an architecture for enabling information sharing with strong security guarantees. It is built upon basic tenets and concepts that shape its component technologies and implementation. One challenge in sharing information is that the source and recipient of the information may use different units, protocols, data formats, or tools to process information. As a result, a transformation of the data is needed before the recipient can use the information. These conversions introduce potential security weaknesses into an ELS system, so an approach for enterprise-wide mediation is required. Methods in common use today, such as a man-in-the-middle (MITM translation and an online mediation service, do not preserve the basic ELS tenets and concepts. This paper examines these existing approaches and compares them with two new approaches designed to preserve ELS security. It looks at the complete picture of security, performance, and ease of implementation, offering a framework for choosing the best mediation approach based on the data sharing context.

  4. 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.

  5. Molecular architecture of the yeast Mediator complex

    Science.gov (United States)

    Robinson, Philip J; Trnka, Michael J; Pellarin, Riccardo; Greenberg, Charles H; Bushnell, David A; Davis, Ralph; Burlingame, Alma L; Sali, Andrej; Kornberg, Roger D

    2015-01-01

    The 21-subunit Mediator complex transduces regulatory information from enhancers to promoters, and performs an essential role in the initiation of transcription in all eukaryotes. Structural information on two-thirds of the complex has been limited to coarse subunit mapping onto 2-D images from electron micrographs. We have performed chemical cross-linking and mass spectrometry, and combined the results with information from X-ray crystallography, homology modeling, and cryo-electron microscopy by an integrative modeling approach to determine a 3-D model of the entire Mediator complex. The approach is validated by the use of X-ray crystal structures as internal controls and by consistency with previous results from electron microscopy and yeast two-hybrid screens. The model shows the locations and orientations of all Mediator subunits, as well as subunit interfaces and some secondary structural elements. Segments of 20–40 amino acid residues are placed with an average precision of 20 Å. The model reveals roles of individual subunits in the organization of the complex. DOI: http://dx.doi.org/10.7554/eLife.08719.001 PMID:26402457

  6. GEOGRAPHICAL EDUCATION MEDIATIZATION AND MEDIASECURITY ISSUES

    Directory of Open Access Journals (Sweden)

    M. R. Arpentieva

    2017-01-01

    Full Text Available The article is devoted to the interaction of legal and moral development of media technologies in the context of geographical education. The article summarizes the experience of the theoretical analysis of mediatization in geographic education, the legal and moral aspects of the disorders and ways of their prevention and correction in the process of educational interaction between teacher and student, between student and teacher, mediated mediatechnologies. It is noted that geographical education in the modern world is education, which is closely associated with the use of media technologies. In other types of education the role of media technologies in improving the quality of education is less obvious, in the field of teaching and learning geography, it speaks very clearly. Therefore, the problems associated with its mediatization, are very important and their solution is particularly compelling. These issues are primarily associated with actively flowing social, economic, political and ideological crisis in many communities and countries of the Earth. Many of them as in the “mirror” are reflected in the sphere of high technologies, including media technologies. The article provides guidance and direction to the correction of violations at the individual and social levels.

  7. Nurse turnover: the mediating role of burnout.

    Science.gov (United States)

    Leiter, Michael P; Maslach, Christina

    2009-04-01

    This study tested whether the mediation model of burnout could predict nurses' turnover intentions. A better understanding of what factors support a commitment to a nursing career could inform both policies and workplace practices. The mediation model of burnout provides a way of linking the quality of a nurse's worklife to various outcomes, such as turnover. Data on areas of worklife, burnout, and turnover intentions were collected by surveying 667 Canadian nurses in the Atlantic Provinces. The findings supported the mediation model of burnout, in which areas of worklife predicted burnout, which in turn predicted turnover intentions. Cynicism was the key burnout dimension for turnover, and the most critical areas of worklife were value conflicts and inadequate rewards. The results of this study provide some new insights into how the intention of nurses to leave their job is related to particular aspects of their worklife and to burnout. These results suggest what may be the most appropriate areas to target for interventions to reduce the risk of nurses exiting early from their chosen career.

  8. Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

    Directory of Open Access Journals (Sweden)

    Laxton Kevin

    2010-05-01

    Full Text Available Abstract Background One pathological hallmark of Alzheimer's disease (AD is amyloid plaques, composed primarily of amyloid-β peptide (Aβ. Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42 in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ has recently emerged to be as a likely proximal cause of AD. Results Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity. Conclusions These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.

  9. Diverse exocytic pathways for mast cell mediators.

    Science.gov (United States)

    Xu, Hao; Bin, Na-Ryum; Sugita, Shuzo

    2018-04-17

    Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells respond to environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g. proteases, amines, and cytokines). Many of these mediators are stored in granules/lysosomes and rely on intricate degranulation processes for release. Mast cell stabilizers (e.g. sodium cromoglicate), which prevent such degranulation processes, have therefore been clinically employed to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators that rely on overlapping but distinct mechanisms for release. This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells. We also discuss strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  10. LDB1-mediated enhancer looping can be established independent of mediator and cohesin.

    Science.gov (United States)

    Krivega, Ivan; Dean, Ann

    2017-08-21

    Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected. Additional deletion of the promoter GATA1 site eliminated LDB1 complex and mediator occupancy and resulted in loss of LCR/β-globin proximity. To separate the roles of LDB1 and mediator in LCR looping, we expressed a looping-competent but transcription-activation deficient form of LDB1 in LDB1 knock down cells: LCR/β-globin proximity was restored without mediator core occupancy. Further, Cas9-directed tethering of mutant LDB1 to the β-globin promoter forced LCR loop formation in the absence of mediator or cohesin occupancy. Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

  11. Two-step estimation in ratio-of-mediator-probability weighted causal mediation analysis.

    Science.gov (United States)

    Bein, Edward; Deutsch, Jonah; Hong, Guanglei; Porter, Kristin E; Qin, Xu; Yang, Cheng

    2018-04-15

    This study investigates appropriate estimation of estimator variability in the context of causal mediation analysis that employs propensity score-based weighting. Such an analysis decomposes the total effect of a treatment on the outcome into an indirect effect transmitted through a focal mediator and a direct effect bypassing the mediator. Ratio-of-mediator-probability weighting estimates these causal effects by adjusting for the confounding impact of a large number of pretreatment covariates through propensity score-based weighting. In step 1, a propensity score model is estimated. In step 2, the causal effects of interest are estimated using weights derived from the prior step's regression coefficient estimates. Statistical inferences obtained from this 2-step estimation procedure are potentially problematic if the estimated standard errors of the causal effect estimates do not reflect the sampling uncertainty in the estimation of the weights. This study extends to ratio-of-mediator-probability weighting analysis a solution to the 2-step estimation problem by stacking the score functions from both steps. We derive the asymptotic variance-covariance matrix for the indirect effect and direct effect 2-step estimators, provide simulation results, and illustrate with an application study. Our simulation results indicate that the sampling uncertainty in the estimated weights should not be ignored. The standard error estimation using the stacking procedure offers a viable alternative to bootstrap standard error estimation. We discuss broad implications of this approach for causal analysis involving propensity score-based weighting. Copyright © 2018 John Wiley & Sons, Ltd.

  12. Redox-Mediated and Ionizing-Radiation-Induced Inflammatory Mediators in Prostate Cancer Development and Treatment

    Science.gov (United States)

    Miao, Lu; Holley, Aaron K.; Zhao, Yanming; St. Clair, William H.

    2014-01-01

    Abstract Significance: Radiation therapy is widely used for treatment of prostate cancer. Radiation can directly damage biologically important molecules; however, most effects of radiation-mediated cell killing are derived from the generated free radicals that alter cellular redox status. Multiple proinflammatory mediators can also influence redox status in irradiated cells and the surrounding microenvironment, thereby affecting prostate cancer progression and radiotherapy efficiency. Recent Advances: Ionizing radiation (IR)–generated oxidative stress can regulate and be regulated by the production of proinflammatory mediators. Depending on the type and stage of the prostate cancer cells, these proinflammatory mediators may lead to different biological consequences ranging from cell death to development of radioresistance. Critical Issues: Tumors are heterogeneous and dynamic communication occurs between stromal and prostate cancer cells, and complicated redox-regulated mechanisms exist in the tumor microenvironment. Thus, antioxidant and anti-inflammatory strategies should be carefully evaluated for each patient at different stages of the disease to maximize therapeutic benefits while minimizing unintended side effects. Future Directions: Compared with normal cells, tumor cells are usually under higher oxidative stress and secrete more proinflammatory mediators. Thus, redox status is often less adaptive in tumor cells than in their normal counterparts. This difference can be exploited in a search for new cancer therapeutics and treatment regimes that selectively activate cell death pathways in tumor cells with minimal unintended consequences in terms of chemo- and radio-resistance in tumor cells and toxicity in normal tissues. Antioxid. Redox Signal. 20, 1481–1500. PMID:24093432

  13. Deflected Mirage Mediation: A Phenomenological Framework for Generalized Supersymmetry Breaking

    International Nuclear Information System (INIS)

    Everett, Lisa L.; Kim, Ian-Woo; Ouyang, Peter; Zurek, Kathryn M.

    2008-01-01

    We present a general phenomenological framework for dialing between gravity mediation, gauge mediation, and anomaly mediation. The approach is motivated from recent developments in moduli stabilization, which suggest that gravity mediated terms can be effectively loop suppressed and thus comparable to gauge and anomaly mediated terms. The gauginos exhibit a mirage unification behavior at a ''deflected'' scale, and gluinos are often the lightest colored sparticles. The approach provides a rich setting in which to explore generalized supersymmetry breaking at the CERN Large Hadron Collider

  14. Is intercultural mediation necessary? An approach from a communications perspective

    Directory of Open Access Journals (Sweden)

    Susana Ridao Rodrigo

    2014-10-01

    Full Text Available Institutionalized intercultural mediation is expanding as a result of the increase in the number of immigrants in our country. Institutionalized intercultural mediation, which started in the early Nineties in Spain, is understood to mean activities carried out by ONGs and by the social services of the host nation. In line with Giménez (1997: 127, we understand intercultural mediation as a modality within the broader field of mediation. Because of its recent expansion, there is not at present a unique methodology accepted by experts in this field. In this paper, our aims are focused on describing various mediation techniques and the possibility of their application within intercultural contexts

  15. Applications of Vygotskyan Concept of Mediation in SLA

    Directory of Open Access Journals (Sweden)

    Carmen Helena Guerrero Nieto

    2011-04-01

    Full Text Available The application of Vygotskian ideas is not new to education, research studies abound reporting various ways in which they can be applied. But in the particular field of Second Language Acquisition a Vygotskian approach is rather new, with the first studies dating from about mid 1990s. In this article I discuss one Vygotskian concept, mediation, and report on some research studies that have been framed in this concept. I found that the studies surveyed could be grouped according to the type of mediation, therefore three categories emerged: Mediation by dialoguing with one self, Mediation by dialoguing with the other, and mediation through technology.

  16. Mediator and moderator effects in developmental and behavioral pediatric research.

    Science.gov (United States)

    Rose, Brigid M; Holmbeck, Grayson N; Coakley, Rachael Millstein; Franks, Elizabeth A

    2004-02-01

    The terms mediation and moderation are defined and clarified with particular emphasis on the role of mediational and moderational analyses in developmental and behavioral pediatric research. The article highlights the applicability of mediational and moderational analyses to longitudinal, intervention, and risk and protective factor research, and it provides basic information about how these analyses might be conducted. Also included is a discussion of various ways that both mediator and moderator variables can be incorporated into a single model. The article concludes with extended examples of both types of analyses using a longitudinal pediatric study for illustration. The article provides recommendations for applying mediational and moderational research in clinical practice.

  17. Predictors of Parental Mediation Regarding Children's Smartphone Use.

    Science.gov (United States)

    Hwang, Yoori; Jeong, Se-Hoon

    2015-12-01

    Children's addiction to smartphones has become a serious issue, and parental mediation could help prevent children's problematic use of smartphones. This research examined the factors that predict and explain parents' intention to mediate children's behavior over smartphone use. Based on a survey of 460 parents of elementary school students, we found that parental mediation was predicted by (a) parent's own addiction to smartphones, (b) perceived severity of smartphone addiction, and (c) personality traits such as neuroticism, openness, and agreeableness. To the best of our knowledge, this study is the first to examine the predictors of parental mediation regarding children's smartphone addiction, and the findings suggest some strategies to increase parental mediation.

  18. Creativity in Court-Connected Mediation: Myth or Reality?

    DEFF Research Database (Denmark)

    Adrian, Lin; Mykland, Solfrid

    2014-01-01

    In this study, we examined creativity in court-connected mediation. We analyzed 129 mediated agreements from civil cases in Norway and Denmark and compared the outcomes with the parties' original claims to determine whether the agreement addressed only the disputants' demands or contained other...... elements. If the mediated agreements contained elements in addition to the original claims, we considered them to be “creative.” We devised a creativity scale and found that approximately two thirds of the cases contained creative elements and one quarter of them contained more than five creative elements....... We then sought to determine which aspects of the mediation promoted creativity by looking at a variety of mediation characteristics (length of mediation, characteristics of the parties, etc.). We found that lengthier mediations tended to feature more creativity as did cases that involved two private...

  19. Demonstration and evaluation of a method for assessing mediated moderation.

    Science.gov (United States)

    Morgan-Lopez, Antonio A; MacKinnon, David P

    2006-02-01

    Mediated moderation occurs when the interaction between two variables affects a mediator, which then affects a dependent variable. In this article, we describe the mediated moderation model and evaluate it with a statistical simulation using an adaptation of product-of-coefficients methods to assess mediation. We also demonstrate the use of this method with a substantive example from the adolescent tobacco literature. In the simulation, relative bias (RB) in point estimates and standard errors did not exceed problematic levels of +/- 10% although systematic variability in RB was accounted for by parameter size, sample size, and nonzero direct effects. Power to detect mediated moderation effects appears to be severely compromised under one particular combination of conditions: when the component variables that make up the interaction terms are correlated and partial mediated moderation exists. Implications for the estimation of mediated moderation effects in experimental and nonexperimental research are discussed.

  20. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros

    Science.gov (United States)

    Valeri, Linda; VanderWeele, Tyler J.

    2012-01-01

    Mediation analysis is a useful and widely employed approach to studies in the field of psychology and in the social and biomedical sciences. The contributions of this paper are several-fold. First we seek to bring the developments in mediation analysis for non linear models within the counterfactual framework to the psychology audience in an accessible format and compare the sorts of inferences about mediation that are possible in the presence of exposure-mediator interaction when using a counterfactual versus the standard statistical approach. Second, the work by VanderWeele and Vansteelandt (2009, 2010) is extended here to allow for dichotomous mediators and count outcomes. Third, we provide SAS and SPSS macros to implement all of these mediation analysis techniques automatically and we compare the types of inferences about mediation that are allowed by a variety of software macros. PMID:23379553