30 research outputs found

    Untersuchungen zur Optimierung von barrierefreien visuellen Kontrasten

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    Die visuelle Barrierefreiheit ist eine Voraussetzung dafür, dass Personen mit Seheinschränkungen selbstständig am öffentlichen Leben teilnehmen können. In Anforderungen und Normen gibt es deshalb Mindestkontraste und Vorgaben für die Reflexionsgrade der Materialen, mit denen die Sehobjekte realisiert werden müssen. Die Anforderungen an die Kontraste sind so groß, dass sie mit vielen Materialen nur schwer erfüllt werden können. Es ist bekannt, dass eine Optimierung der Beleuchtung dazu führt, dass auch weniger hohe Kontraste sicher erkannt werden. Dazu zählen die Erhöhung der Leuchtdichte und die Vermeidung von Blendung. Im Rahmen einer Forschung wurde ein Teststand entwickelt, mit dem die Parameter gezielt variiert werden konnten und an Testpersonen Untersuchungen zum Kontrastsehen durchgeführt wurden. Die Erhöhung der Umfeldleuchtdichte führte dabei zu einer Verbesserung der Wahrnehmung von Kontrasten. Trotz Erhöhung der Umfeldleuchtdichte konnte nicht jeder Kontrast von allen Probanden erkannt werden. Direktblendung führt dazu, dass Kontraste schlechter wahrgenommen wurden

    Untersuchungen zur Optimierung von barrierefreien visuellen Kontrasten

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    Die visuelle Barrierefreiheit ist eine Voraussetzung dafür, dass Personen mit Seheinschränkungen selbstständig am öffentlichen Leben teilnehmen können. In Anforderungen und Normen gibt es deshalb Mindestkontraste und Vorgaben für die Reflexionsgrade der Materialen, mit denen die Sehobjekte realisiert werden müssen. Die Anforderungen an die Kontraste sind so groß, dass sie mit vielen Materialen nur schwer erfüllt werden können. Es ist bekannt, dass eine Optimierung der Beleuchtung dazu führt, dass auch weniger hohe Kontraste sicher erkannt werden. Dazu zählen die Erhöhung der Adaptations-Leuchtdichte und die Vermeidung von Blendung. Im Rahmen einer Forschung wurde ein Teststand entwickelt, mit dem die Parameter gezielt variiert werden können und an dem mit Testpersonen Untersuchungen zum Kontrastsehen durchgeführt werden. Es werden das Testkonzept und erste Ergebnisse vorgestellt

    Screening a mushroom extract library for activity against Acinetobacter baumannii and Burkholderia cepacia and the identification of a compound with anti-Burkholderia activity

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    <p>Abstract</p> <p>Background</p> <p><it>Acinetobacter baumannii </it>and species within the <it>Burkholderia cepacia </it>complex (BCC) are significant opportunistic bacterial pathogens of humans. These species exhibit a high degree of antibiotic resistance, and some clinical isolates are resistant to all currently available antimicrobial drugs used for treatment. Thus, new drugs are needed to treat infections by these species. Mushrooms could be a potential source for new drugs to treat <it>A. baumannii </it>and BCC infections.</p> <p>Methods</p> <p>The aim of this study was to screen a library of crude extracts from 330 wild mushrooms by disk diffusion assays for antibacterial activity against <it>A. baumannii </it>and <it>Burkholderia cepacia </it>in the hope of identifying a novel natural drug that could be used to treat infections caused by these species. Once positive hits were identified, the extracts were subjected to bioassay-guided separations to isolate and identify the active drug molecules. MICs were performed to gauge the <it>in vitro </it>activity of the purified compounds.</p> <p>Results</p> <p>Only three crude extracts (0.9%) had activity against <it>A. baumannii </it>and <it>B. cepacia</it>. Compounds from two of these extracts had MICs greater than 128 μg/ml, and further analyses were not performed. From the third extract, prepared from <it>Leucopaxillus albissimus</it>, 2-aminoquinoline (2-AQ) was isolated. This compound exhibited a modest MIC <it>in vitro </it>against strains from nine different BCC species, including multi-drug resistant clinical isolates (MIC = 8-64 μg/ml), and a weak MIC (128 μg/ml) against <it>A baumannii</it>. The IC<sub>50 </sub>against a murine monocyte line was 1.5 mg/ml.</p> <p>Conclusion</p> <p>The small number of positive hits in this study suggests that finding a new drug from mushrooms to treat Gram-negative bacterial infections may be difficult. Although 2-AQ was identified in one mushroom, and it was shown to inhibit the growth of multi-drug resistant BCC isolates, the relatively high MICs (8-128 μg/ml) for both <it>A. baumannii </it>and BCC strains suggests that 2-AQ is not suitable for further drug development in its current form.</p

    Harnessing the NEON data revolution to advance open environmental science with a diverse and data-capable community

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    It is a critical time to reflect on the National Ecological Observatory Network (NEON) science to date as well as envision what research can be done right now with NEON (and other) data and what training is needed to enable a diverse user community. NEON became fully operational in May 2019 and has pivoted from planning and construction to operation and maintenance. In this overview, the history of and foundational thinking around NEON are discussed. A framework of open science is described with a discussion of how NEON can be situated as part of a larger data constellation—across existing networks and different suites of ecological measurements and sensors. Next, a synthesis of early NEON science, based on >100 existing publications, funded proposal efforts, and emergent science at the very first NEON Science Summit (hosted by Earth Lab at the University of Colorado Boulder in October 2019) is provided. Key questions that the ecology community will address with NEON data in the next 10 yr are outlined, from understanding drivers of biodiversity across spatial and temporal scales to defining complex feedback mechanisms in human–environmental systems. Last, the essential elements needed to engage and support a diverse and inclusive NEON user community are highlighted: training resources and tools that are openly available, funding for broad community engagement initiatives, and a mechanism to share and advertise those opportunities. NEON users require both the skills to work with NEON data and the ecological or environmental science domain knowledge to understand and interpret them. This paper synthesizes early directions in the community’s use of NEON data, and opportunities for the next 10 yr of NEON operations in emergent science themes, open science best practices, education and training, and community building

    Challenges to Funding School Facilities in Colorado

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    Appalling conditions have existed in Colorado schools for many years. Yet Colorado, like many other states, has shifted its priority from adequately funding schools to tax refunds. This article gives an overview of Colorado facilities-funding challenges, followed by an account of the Giardino v. Colorado State Board of Education litigation, the author’s involvement in it, and the aftermath of the settlement reached

    Epigenetische Kontrolle meiotischer Rekombination und Kartierung neuer Su(var)-Gene in Drosophila melanogaster

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    Die Neukombination väterlicher und mütterlicher Gene wird während der Meiose durch den Prozess der homologen Rekombination vermittelt. Heterochromatin hat als ein regulatorischer Aspekt meiotischer Rekombinationsprozesse einen negativen Effekt auf Crossover, wodurch eine signifikante Reduktion von Rekombinationsereignissen vor allem in heterochromatischen Bereichen stattfindet. Somit sollten Faktoren, die die Chromatinstruktur beeinflussen, folglich auch die Crossoverfrequenz verändern. Diese Faktoren können bei Drosophila melanogaster durch das System der Positionseffekt-Variegation (PEV) identifiziert werden. Eine Vielzahl der PEV-Faktoren zeigt in diesem Zusammenhang einen rekombinogenen Effekt auf das perizentrische Hetereochromatin. In der vorliegenden Arbeit sollen am Modellsystem Drosophila melanogaster mit Hilfe genetischer, immunzytologischer und molekularbiologischer Analysen epigenetische Prozesse aufgeklärt werden, die die meiotische Rekombination beeinflussen. Weiterhin wurden neue Kartierungsmethoden zur effizienten Identifizierung neuer epigenetischer Faktoren etabliert.The new combination of paternal and maternal genes is arranged by the process of homologous recombination during meiosis. As its regulatory aspect of meiotic recombination heterochromatin has a negativ effect on crossover, whereby a significant reduction of crossover occur in heterochromatic regions. Consequently factors, which influence chromatin structure, should therefore also change crossover frequency. These factors can be identified by the system of position effect variegation (PEV) among Drosophila melanogaster. In connection with this, a variety of PEV factors show recombinogentic effects on pericentric heterochromatin. The present work consists in resolution of epigenetic processes controlling meiotic recombination by genetic, immunocytological and molecular analysis using the Drosophila melanogaster model system. Furthermore new mapping methods were established for efficient identification of new epigenetic factors.von Kathleen Gebhard

    Resistance to BRAF Inhibitors: EZH2 and Its Downstream Targets as Potential Therapeutic Options in Melanoma

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    Activating BRAF mutations occurs in 50–60% of malignant melanomas. Although initially treatable, the development of resistance to BRAF-targeted therapies (BRAFi) is a major challenge and limits their efficacy. We have previously shown that the BRAFV600E signaling pathway mediates the expression of EZH2, an epigenetic regulator related to melanoma progression and worse overall survival. Therefore, we wondered whether inhibition of EZH2 would be a way to overcome resistance to vemurafenib. We found that the addition of an EZH2 inhibitor to vemurafenib improved the response of melanoma cells resistant to BRAFi with regard to decreased viability, cell-cycle arrest and increased apoptosis. By next-generation sequencing, we revealed that the combined inhibition of BRAF and EZH2 dramatically suppresses pathways of mitosis and cell cycle. This effect was linked to the downregulation of Polo-kinase 1 (PLK1), a key regulator of cell cycle and proliferation. Subsequently, when we inhibited PLK1, we found decreased cell viability of melanoma cells resistant to BRAFi. When we inhibited both BRAF and PLK1, we achieved an improved response of BRAFi-resistant melanoma cells, which was comparable to the combined inhibition of BRAF and EZH2. These results thus reveal that targeting EZH2 or its downstream targets, such as PLK1, in combination with BRAF inhibitors are potential novel therapeutic options in melanomas with BRAF mutations

    Resistance to BRAF Inhibitors: EZH2 and Its Downstream Targets as Potential Therapeutic Options in Melanoma

    No full text
    Activating BRAF mutations occurs in 50&ndash;60% of malignant melanomas. Although initially treatable, the development of resistance to BRAF-targeted therapies (BRAFi) is a major challenge and limits their efficacy. We have previously shown that the BRAFV600E signaling pathway mediates the expression of EZH2, an epigenetic regulator related to melanoma progression and worse overall survival. Therefore, we wondered whether inhibition of EZH2 would be a way to overcome resistance to vemurafenib. We found that the addition of an EZH2 inhibitor to vemurafenib improved the response of melanoma cells resistant to BRAFi with regard to decreased viability, cell-cycle arrest and increased apoptosis. By next-generation sequencing, we revealed that the combined inhibition of BRAF and EZH2 dramatically suppresses pathways of mitosis and cell cycle. This effect was linked to the downregulation of Polo-kinase 1 (PLK1), a key regulator of cell cycle and proliferation. Subsequently, when we inhibited PLK1, we found decreased cell viability of melanoma cells resistant to BRAFi. When we inhibited both BRAF and PLK1, we achieved an improved response of BRAFi-resistant melanoma cells, which was comparable to the combined inhibition of BRAF and EZH2. These results thus reveal that targeting EZH2 or its downstream targets, such as PLK1, in combination with BRAF inhibitors are potential novel therapeutic options in melanomas with BRAF mutations

    The role of personality factors in young adults’ motives for sharing alcohol references on social networking sites

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    Sharing alcohol-related content on social media has been linked to young adults’ alcohol use. Therefore, it is important to understand why these references are shared in the first place. As such, the first aim of this study was to identify the motives (social, entertainment, information/identification) that predict the sharing of alcohol references through an online survey of young Dutch adults (N = 339, Mage = 22.67 years, SDage = 3.04 years, 69.4% women). The second aim was to investigate individual differences in motives by examining whether motives mediate the relationship between personality traits (agreeableness, neuroticism, extroversion) and internal states (need for popularity) and sharing alcohol-related content. Our findings showed that identification/information (and not social or entertainment) motives and extroversion directly predicted the sharing of alcohol-related content. Moreover, respondents with a great need for popularity scored higher on all sharing motives, but only identification/information motives mediated the relationship between the need for popularity and sharing alcohol-related content. Thus, extroverted and popularity-oriented individuals are highly likely to post alcohol-related content. Overall, our findings show that certain motives predict the sharing of alcohol references on social media and that certain groups of individuals may be particularly prone to sharing such content, which makes them potential targets for interventions
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