14,588 research outputs found

    Business on television: continuity, change and risk in the development of television’s ‘business entertainment format’

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    This article traces the evolution of what has become known as the business entertainment format on British television. Drawing on interviews with channel controllers, commissioners and producers from across the BBC, Channel 4 and the independent sector this research highlights a number of key individuals who have shaped the development of the business entertainment format and investigates some of the tensions that arise from combining entertainment values with more journalistic or educational approaches to factual television. While much work has looked at docusoaps and reality programming, this area of television output has remained largely unexamined by television scholars. The research argues that as the television industry has itself developed into a business, programme-makers have come to view themselves as [creative] entrepreneurs thus raising the issue of whether the development off-screen of a more commercial, competitive and entrepreneurial TV marketplace has impacted on the way the medium frames its onscreen engagement with business, entrepreneurship, risk and wealth creation

    Differential regulation of anti-inflammatory genes by p38 MAP kinase and MAP kinase kinase 6.

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    BackgroundConventional p38α inhibitors have limited efficacy in rheumatoid arthritis, possibly because p38 blockade suppresses the counter-regulatory mechanisms that limit inflammation. In contrast, targeting the upstream MAP kinase kinases, MKK3 and MKK6, partially maintains p38-mediated anti-inflammatory responses in bone marrow-derived macrophages (BMDM). In this study, we explored the mechanisms that preserve anti-inflammatory gene expression by evaluating differential regulation of IL-10 and p38-dependent anti-inflammatory genes in MKK3-/-, MKK6-/-, and p38 inhibitor-treated wildtype cells.MethodsBMDM from wild type (WT), MKK3-/-, and MKK6-/- mice were pre-treated with p38 inhibitor SB203580 (SB), JNK inhibitor SP600125 (SP), and/or ERK inhibitor PD98059 (PD) and stimulated with LPS. Supernatant protein levels were measured by multiplex bead immunoassay. mRNA expression was determined by qPCR and protein expression by Western blot analysis. De novo IL-10 mRNA synthesis was quantified in cells treated with ethynyl-uridine and LPS followed by reverse transcription and qPCR. mRNA half-life was measured in LPS-treated cells that were then incubated with actinomycin D ± SB203580.ResultsPre-treatment of WT BMDM with p38 inhibitor significantly reduced IL-10 production in the three groups, while ERK and JNK inhibitors had minimal effects. IL-10 production was significantly decreased in MKK3-/- BMDM compared with either WT or MKK6-/- cells. IL-10 mRNA expression was modestly reduced in MKK3-/- BMDM but was preserved in MKK6-/- cells compared with WT. De novo IL-10 mRNA synthesis was inhibited in MKK3-/- and p38 inhibitor pre-treated cells, but not MKK6-/- cells compared with WT. IL-10 mRNA half-life was markedly reduced in p38 inhibitor-treated WT cells while MKK-deficiency had minimal effect. DUSP1 mRNA levels were preserved in MKK-deficient cells but not in p38 inhibitor-treated WT cells. Tristetraprolin mRNA and protein levels were reduced in p38 inhibitor-treated WT cells compared with MKK6-/- cells.ConclusionUnlike p38-inhibition, the absence of MKK6 mostly preserves IL-10 and TTP protein expression in BMDM. MKK6-deficiency also spares DUSP1 and IL-1RA, which are key negative regulators of the inflammatory response. Together, these data suggest that MKK6 is a potential therapeutic target in RA

    Missing A Lance Corporal

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    Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes.

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    c-Jun N-terminal kinase (JNK) contributes to metalloproteinase (MMP) gene expression and joint destruction in inflammatory arthritis. It is phosphorylated by at least two upstream kinases, the mitogen-activated protein kinase kinases (MEK) MKK4 and MKK7, which are, in turn, phosphorylated by MEK kinases (MEKKs). However, the MEKKs that are most relevant to JNK activation in synoviocytes have not been determined. These studies were designed to assess the hierarchy of upstream MEKKs, MEKK1, MEKK2, MEKK3, and transforming growth factor-beta activated kinase (TAK)1, in rheumatoid arthritis (RA). Using either small interfering RNA (siRNA) knockdown or knockout fibroblast-like synoviocytes (FLSs), MEKK1, MEKK2, or MEKK3 deficiency (either alone or in combination) had no effect on IL-1beta-stimulated phospho-JNK (P-JNK) induction or MMP expression. However, TAK1 deficiency significantly decreased P-JNK, P-MKK4 and P-MKK7 induction compared with scrambled control. TAK1 knockdown did not affect p38 activation. Kinase assays showed that TAK1 siRNA significantly suppressed JNK kinase function. In addition, MKK4 and MKK7 kinase activity were significantly decreased in TAK1 deficient FLSs. Electrophoretic mobility shift assays demonstrated a significant decrease in IL-1beta induced AP-1 activation due to TAK1 knockdown. Quantitative PCR showed that TAK1 deficiency significantly decreased IL-1beta-induced MMP3 gene expression and IL-6 protein expression. These results show that TAK1 is a critical pathway for IL-1beta-induced activation of JNK and JNK-regulated gene expression in FLSs. In contrast to other cell lineages, MEKK1, MEKK2, and MEKK3 did not contribute to JNK phosphorylation in FLSs. The data identify TAK1 as a pivotal upstream kinase and potential therapeutic target to modulate synoviocyte activation in RA

    A META ANALYSIS OF CONTINGENT VALUES FOR GROUNDWATER QUALITY IN THE UNITED STATES

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    This paper provides an overview and a meta analysis of existing US contingent valuation studies of groundwater quality. Using 108 observations from 14 studies, core economic variables, risk variables, and elicitation effects are found to systematically influence groundwater values. Other research design features are also investigated.Resource /Energy Economics and Policy,

    An Investigation of the Metallic Derivatives of Ortho-Substituted Azo Compounds

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    The investigation of the mono-o-hydroxyazo compounds showed that these compounds formed metallic derivatives with comparative ease. This seems to be in accord with the concensus of published work on the subject, though disputed by some of the foremost investigators. An interesting point that arose, was that copper seems unable to form a complex with mono-o-hydroxyazo sulphonic acids, unless the sulphonic acid group has been neutralised. In this respect, this class is inferior in lake forming properties to the di-o-hydroxyazo compounds. It appears that, in general, with o:o'-dihydroxyazo compounds metallisation results in the formation of typical inner complex compounds, both hydroxyl groups acting as acidic groups and either one or both of the azo nitrogen atoms co-ordinating with the metal. However, the experiments have led also to the conclusion that, several different derivatives of the same metal can be prepared from the one dyestuff; the differences being in the proportion of metal combined with the dyestuff and being accounted for by one of the following reasons; free sulphonic acid group; metal retaining within the complex some residual basicity; some of the hydroxyl groups may not have combined with the metal through hydrogen replacement, but merely by co-ordination. The experiments with primary and secondary complexes leads to the following suggested mechanism for the conversion of one to the other. Primary complexes contain monobasic chromium. The first reaction in the passage of a primary into a secondary complex is the formation of the free sulphonic acid of the former and this combines with the monobasic chromium already in the complex to give an even more internally bound inner complex salt. The above represents the suggested course of the change. When taking into account the co-ordinate links between the metal and the azo nitrogen atoms, it is apparent that a compound represented as the secondary one is, would be linked to the dyestuff molecule at five points. Such quinquidentate chelate compounds do not seem to have been recorded in the literature hitherto. The claims in the patent literature were confirmed that an o-alkyloxy group can give rise to metallic derivatives, if the conditions of the reaction are such as first to hydrolyse the alkyloxy group. This can be done by metallising under pressure - a method which was found to facilitate complex formation and to encourage the maximum combination between dyestuff and metal. In the o-carboxyl-o-hydroxyazo compounds, it was found that an o-carboxyl group, though it resembles an o-hydroxyl, results in the formation of a slightly less stable link between the azo compound and the metal. The experiments with toluylene Brown G indicated that an amino group o-to the azo link acts similarly to an hydroxyl group, i.e. by hydrogen displacement displacement it can combine with copper or chromium forming part of a chelate group and there were no signs of triazol formation. The reactions of Chrome Brown T.V. (in which there is both an o-amino and an o-hydroxyl group) supported this conclusion. The test with the Grignard Reagent showed that chromium lakes sometimes contain the metal in a monobasic state
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