234 research outputs found
Scenarios for the Internet Migration of the Television Industry
All the conditions for the television industry’s migration to the Internet are now in place. While this migration will be gradual, it will have a deep-seated impact on the industry:•the exclusive rights model will no longer be the standard;•some consumers will abandon traditional managed networks;•a globalization trend will be sparked, to the benefit of the major rights holders. Unlike the music and print media industries, the TV industry is gaining a strong position on the Web. As a result, television is poised to play a central role in video services. This offensive strategy will likely pay off down the line, but does not entirely eliminate the possibility of destroying value. There are structural reasons for this, including a fiercely competitive online advertising market and a lack of control over program circulation. Far from being simply transitory, the 2009-2010 economic downturn marks the beginning of a decade of restructuring for the TV industry. This new period will begin with an overall decline in the sector’s resources before increasingly varied consumption patterns spur a new period of growth. The decade running from 2010 to 2020 will also be a period that focuses on cost control, with the industrialization of TV production that will depart once and for all from its historical model, i.e., film. This migration to the Web poses a threat to the European industry in particular. A reassessment of the television industry’s regulatory strategy appears both necessary and urgent, and will involve the creation of integrated pan-European conglomerates.Television, video, networks, on-demand, connected devices, advertising, pay-TV.
Conditions hydrologiques de la zone frontale du Cap Lopez pendant la campagne thonière de juin-juillet 1971
An Updated View on an Emerging Target: Selected Papers from the 8th International Conference on Protein Kinase CK2
The 8th International Conference on Protein Kinase CK2 took place in Homburg, Germany, from 6 September to 9 September 2016. Over 80 scientists from Australia, China, Japan, USA, Canada, Denmark, France, Italy, Spain, Poland and Germany participated. After the opening lecture by Lorenzo A. Pinna, Padova, Italy, entitled Exploring the CK2 Paradox: Restless, Dangerous, Dispensable, the scientists reported their latest research on the structural characterization of CK2, hence leading directly to the development of CK2 inhibitors. The driving force behind the development of inhibitors is their use in the treatment of various diseases, which was the next topic of the conference. New findings on protein kinase CK2 were addressed in the following session. The final topic of the conference addressed the role of CK2 in differentiation and development
Aprendizaje cooperativo: una nueva metodologĂa motivadora para el alumno
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Inhibition of Shiga toxin-converting bacteriophage development by novel antioxidant compounds
Oxidative stress may be the major cause of induction of Shiga toxin-converting (Stx) prophages from chromosomes of Shiga toxin-producing Escherichia coli (STEC) in human intestine. Thus, we aimed to test a series of novel antioxidant compounds for their activities against prophage induction, thus, preventing pathogenicity of STEC. Forty-six compounds (derivatives of carbazole, indazole, triazole, quinolone, ninhydrine, and indenoindole) were tested. Fifteen of them gave promising results and were further characterized. Eleven compounds had acceptable profiles in cytotoxicity tests with human HEK-293 and HDFa cell lines. Three of them (selected for molecular studies) prevent the prophage induction at the level of expression of specific phage genes. In bacterial cells treated with hydrogen peroxide, expression of genes involved in the oxidative stress response was significantly less efficient in the presence of the tested compounds. Therefore, they apparently reduce the oxidative stress, which prevents induction of Stx prophage in E. coli
Innovation in smallholder farming in Africa: recent advances and recommendations: Proceedings of the International Workshop on Agricultural Innovation Systems in Africa (AISA)
In the wake of a series of recent international events and initiatives focusing on understanding and fostering innovation1, there is growing awareness and interest in applying and making sense of the Agricultural Innovation Systems (AIS) concepts and perspectives and what they offer for understanding and supporting innovation systems, processes and networks. This has particular relevance for African agriculture as it faces several challenges, such as increasing and intensifying food production in a sustainable way and nourishing its fast-growing population, adapting to the consequences of climate change, and finding its rightful place in an increasingly global and complex international scene. Several initiatives and programmes seeking answers to these questions jointly organised a series of events during a Week on Agricultural Innovation in Africa (WAIA) held in Nairobi, Kenya, on 25–31 May 2013, of which the international workshop on Agricultural Innovation Systems in Africa (AISA) on 29–31 May was a major part. Another key event during this week, was the Eastern African Farmer Innovation Fair (EAFIF) held on 28–29 May, which was linked to AISA
Functional display of heterotetrameric human protein kinase CK2 on Escherichia coli: a novel tool for drug discovery
Background: Human protein kinase CK2 represents a novel therapeutic target for neoplastic diseases. Inhibitors are in need to explore the druggability and the therapeutic options of this enzyme. A bottleneck in the search for new inhibitors is the availability of the target for testing. Therefore an assay was developed to provide easy access to CK2 for discovery of novel inhibitors. Results: Autodisplay was used to present human CK2 on the surface of Escherichia coli. Heterotetrameric CK2 consists of two subunits, α and β, which were displayed individually on the surface. Co-display of CK2α and CK2β on the cell surface led to the formation of functional holoenzyme, as demonstrated by NaCl dependency of enzymatic activity, which differs from that of the catalytic subunit CK2α without β. In addition interaction of CK2α and CK2β at the cell surface was confirmed by co-immunoprecipitation assays. Surface displayed CK2 holoenzyme enabled an easy IC50 value determination. The IC50 values for the known CK2 inhibitors TBB and Silmitasertib were determined to be 50 and 3.3 nM, respectively. Conclusion: Surface-displayed CK2α and CK2β assembled on the cell surface of E. coli to an active tetrameric holoenzyme. The whole-cell CK2 autodisplay assay as developed is suitable for inhibition studies. Furthermore, it can be used to determine quantitative CK2 inhibition data such as IC50 values. In summary, this is the first report on the functional surface display of a heterotetrameric enzyme on E. coli.<br
1D NMR WaterLOGSY as an efficient method for fragment-based lead discovery
WaterLOGSY is a sensitive ligand-observed NMR experiment for detection of interaction between a ligand and a protein and is now well-established as a screening technique for fragment-based lead discovery. Here we develop and assess a protocol to derive ligand epitope mapping from WaterLOGSY data and demonstrate its general applicability in studies of fragment-sized ligands binding to six different proteins (glycogen phosphorylase, protein peroxiredoxin 5, Bcl-xL, Mcl-1, HSP90, and human serum albumin). We compare the WaterLOGSY results to those obtained from the more widely used saturation transfer difference experiments and to the 3D structures of the complexes when available. In addition, we evaluate the impact of ligand labile protons on the WaterLOGSY data. Our results demonstrate that the WaterLOGSY experiment can be used as an additional confirmation of the binding mode of a ligand to a protein
Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2
Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitorsFil: Guillon, Jean. Universite de Bordeaux; Francia;Fil: Le Borgne, Marc. Université de Lyon; Francia;Fil: Rimbault, Charlotte. Universite de Bordeaux; Francia;Fil: Moreau, Stéphane. Universite de Bordeaux; Francia;Fil: Savrimoutou, Solène. Universite de Bordeaux; Francia;Fil: Pinaud, Noël. Universite de Bordeaux; Francia;Fil: Baratin, Sophie. Universite de Bordeaux; Francia;Fil: Marchivie, Mathieu. Universite de Bordeaux; Francia;Fil: Roche, Séverine. Universite de Bordeaux; Francia;Fil: Bollacke, Andre. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania;Fil: Pecci, Adali. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Fisiol., Biol.molecular y Neurociencias; Argentina;Fil: Alvarez, Lautaro Damian. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unid.microanal.y Met.fisicos En Quim.org.(i); Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Organica;Fil: Desplat, Vanessa. Universite de Bordeaux; Francia;Fil: Joachim, Jose. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania
Distinct intracellular motifs of Delta mediate its ubiquitylation and activation by Mindbomb1 and Neuralized
Ubiquitylation of the intracellular domain of Drosophila Delta is necessary for Notch activation
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