245 research outputs found

    Social Media Monitoring als Instrument der Kontrolle des Internet-Marketing

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    Social Media Monitoring (SMM) ist ein aktuelles und bedeutendes Thema im Bereich der Kontrolle des Internet-Marketing, und wird als Instrument der Erfolgskontrolle und zur Analyse von Maßnahmen des Unternehmens eingesetzt, (z.B.: Public Relation-Maßnahmen/Werbekampagnen). Zahlreiche kostenpflichtige und kostenlose Monitoring Tools ermöglichen Unternehmen GesprĂ€che und Diskussionen im Social Web zu analysieren. Aufwendige und teure Studien zu Marktzwecken werden eben durch das schnelle, kostengĂŒnstige und gezielte Marktforschungsinstrument ergĂ€nzt oder gĂ€nzlich aus den Unternehmensbereichen abgelöst. Gegenstand dieser Arbeit ist, das SMM als Instrument der Analyse der VorgĂ€nge in Social Media, in Bezug auf das Internet-Marketing. Diese Arbeit befasst sich mit den GrĂŒnden vom Einsatz von Social Media Monitoring, Lösungen und deren Tools. Im Zuge dieser Arbeit werden die verschiedenen Tools vorgestellt. Es wird auch deutlich, dass keine optimale Lösung fĂŒr ein Unternehmen existiert, denn es gibt kein einheitliches Tool fĂŒr alle Anwendungsbereiche im Unternehmen

    Macroalgae fouling community as quality element for the evaluation of the ecological status in Vela Luka Bay, Croatia

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    One year qualitative and quantitative study of communities of three major taxonomic groups has been carried out at test panles placed in the upper infarlittoral zone of coastal area of Vela Luka Bay, Croatia. A list of 44 taxa was recorded. Chaetomorpha sp., Ulva sp., Fosliella farinosa, Sphacelaria cirrosa, Polysiphonia scopulorum were the most frequent dominant taxa. Among 27 algal taxa with noticeable presence only three were classified as ESG (Ecological State Groups) I. Low diversity and species richness together with massive presence of the green algae (as Ulva sp.) and negligible presence of ESG I taxa, may lead to erroneous conclusion that Vela Luka Bay is eutrophicated area. Low values of biomass and R/P (Rhodophyceae by Phaeophyceae ratio) Index together with dominance of Phaeophyta also support conclusion that there is no negative impact of nutrient enrichment on macrophyta fouling community in Vela Luka Bay

    ATR‐101 inhibits cholesterol efflux and cortisol secretion by ATP‐binding cassette transporters, causing cytotoxic cholesterol accumulation in adrenocortical carcinoma cells

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    Background and PurposeTo further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR‐101 (PD132301‐02).Experimental ApproachWe compared the effects of ATR‐101, PD129337, and ABC transporter inhibitors on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC‐derived cell lines. We examined the effects of these compounds in combination with methyl‐ÎČ‐cyclodextrin or exogenous cholesterol to determine the roles of altered cholesterol levels in the effects of these compounds.Key ResultsATR‐101 caused cholesterol accumulation, ATP depletion, and caspase activation within 30 minutes after addition to ACC‐derived cells, whereas PD129337 did not. Suppression of cholesterol accumulation by methyl‐ÎČ‐cyclodextrin or exogenous cholesterol, prevented ATP depletion and caspase activation by ATR‐101. ATR‐101 blocked cholesterol efflux and cortisol secretion, suggesting that it inhibited ABCA1, ABCG1, and MDR1 transporters. Combinations of ABCA1, ABCG1, and MDR1 inhibitors were also cytotoxic. Combinations of ATR‐101 with inhibitors of ABCG1, MDR1, or mitochondrial functions had increased cytotoxicity. Inhibitors of steroidogenesis reduced ATP depletion by ATR‐101, whereas U18666A enhanced cholesterol accumulation and ATP depletion together with ATR‐101. ATR‐101 repressed ABCA1, ABCG1, and IDOL transcription by mechanisms that were distinct from the mechanisms that caused cholesterol accumulation.Conclusions and ImplicationsInhibition of multiple ABC transporters and the consequent accumulation of cholesterol mediated the cytotoxicity of ATR‐101. Compounds that replicate these effects in tumours are likely to be useful in the treatment of ACC.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138270/1/bph13951-sup-0001-supplementary_material.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138270/2/bph13951_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138270/3/bph13951.pd

    Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate

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    Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10-13; adjusted p= 2.2 x 10-3). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 – 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans

    Effect Of Exogenous Cholesterol And Dithiothreitol On The Activity Of Human Liver Microsomal Acyl-Coenzyme A:Cholesterol Acyltransferase (ACAT)

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    esterification of cholesterol with long-chain fatty acyl-CoA derivatives and has been implicated in atherosclerosis and gallstone disease. The effects of exogenous cholesterol and dithiothreitol (DTT) on the ACAT activity of human liver microsomes have been determined. Pre-incubation of microsomes with exogenous cholesterol gave a marked stimulation of activity. Experiments with [3H]cholesterol and [14C]ololeoyl-CoA indicated the time course of equilibration of exogenous with endogenous cholesterol as ACAT substrates, and showed that ACAT activity could be accurately measured using [3H]cholesterol/Tween 80, provising that the concentration of endogenous microsomal cholesterol was also determined. Pre-incubation of liver microsomes for 90 min in the presence of 2 mmol/1 DTT and exogenous cholesterol/Tween 80 resulted in a 60% reduction in ACAT activity, compared with the corresponding activity when DTT was omitted. If microsomes were pre-incubated with DTT prior to the pre-incubation with exogenous cholesterol/Tween 80, and 85–90% reduction in ACAT activity occurred. In contrast, pre-incubation of microsomes with DTT in the absence of exogenous cholesterol/Tween 80 (only endogenous cholesterol present) resulted, initially in a stimulation of ACAT activity; on further pre-incubation, activity returned to control levels. These results indicate that the supply of cholesterol to the enzyme active site is an important factor in ACAT assays in vitro and that DTT has a major effect on this process, suggesting that these factors may be important in controlling ACAT activity in vivo

    Mechanisms and targets of the modulatory action of S-nitrosoglutathione (GSNO) on inflammatory cytokines expression.

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    A number of experimental studies has documented that S-nitrosoglutathione (GSNO), the main endogenous low-molecular weight S-nitrosothiol, can exert modulatory effects on inflammatory processes, thus supporting its potential employment in medicine for the treatment of important disease conditions. At molecular level, GSNO effects have been shown to modulate the activity of a series of transcription factors (notably NF-jB, AP-1, CREB and others) as well as other components of signal transduction chains (e.g. IKK-b, caspase 1, calpain and others), resulting in the modulation of several cytokines and chemokines expression (TNFa, IL-1b, IFN-c, IL-4, IL-8, RANTES, MCP-1 and others). Results reported to date are however not univocal, and a single main mechanism of action for the observed anti-inflammatory effects of GSNO has not been identified. Conflicting observations can be explained by differences among the various cell types studies as to the relative abundance of enzymes in charge of GSNO metabolism (GSNO reductase, c-glutamyltransferase, protein disulfide isomerase and others), as well as by variables associated with the individual experimental models employed. Altogether anti-inflammatory properties of GSNO seem however to prevail, and exploration of the therapeutic potential of GSNO and analogues appears therefore warranted
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