875 research outputs found

    Fluorescence-based incision assay for human XPF-ERCC1 activity identifies important elements of DNA junction recognition

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    The structure-specific endonuclease activity of the human XPF–ERCC1 complex is essential for a number of DNA processing mechanisms that help to maintain genomic integrity. XPF–ERCC1 cleaves DNA structures such as stem–loops, bubbles or flaps in one strand of a duplex where there is at least one downstream single strand. Here, we define the minimal substrate requirements for cleavage of stem–loop substrates allowing us to develop a real-time fluorescence-based assay to measure endonuclease activity. Using this assay, we show that changes in the sequence of the duplex upstream of the incision site results in up to 100-fold variation in cleavage rate of a stem-loop substrate by XPF-ERCC1. XPF–ERCC1 has a preference for cleaving the phosphodiester bond positioned on the 3′-side of a T or a U, which is flanked by an upstream T or U suggesting that a T/U pocket may exist within the catalytic domain. In addition to an endonuclease domain and tandem helix–hairpin–helix domains, XPF has a divergent and inactive DEAH helicase-like domain (HLD). We show that deletion of HLD eliminates endonuclease activity and demonstrate that purified recombinant XPF–HLD shows a preference for binding stem–loop structures over single strand or duplex alone, suggesting a role for the HLD in initial structure recognition. Together our data describe features of XPF–ERCC1 and an accepted model substrate that are important for recognition and efficient incision activity

    Library Analytics: Shaping the Future — Data, Privacy and the User Experience

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    The Mirage of Triangular Arbitrage in the Spot Foreign Exchange Market

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    We investigate triangular arbitrage within the spot foreign exchange market using high-frequency executable prices. We show that triangular arbitrage opportunities do exist, but that most have short durations and small magnitudes. We find intra-day variations in the number and length of arbitrage opportunities, with larger numbers of opportunities with shorter mean durations occurring during more liquid hours. We demonstrate further that the number of arbitrage opportunities has decreased in recent years, implying a corresponding increase in pricing efficiency. Using trading simulations, we show that a trader would need to beat other market participants to an unfeasibly large proportion of arbitrage prices to profit from triangular arbitrage over a prolonged period of time. Our results suggest that the foreign exchange market is internally self-consistent and provide a limited verification of market efficiency

    Temporal Evolution of Financial Market Correlations

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    We investigate financial market correlations using random matrix theory and principal component analysis. We use random matrix theory to demonstrate that correlation matrices of asset price changes contain structure that is incompatible with uncorrelated random price changes. We then identify the principal components of these correlation matrices and demonstrate that a small number of components accounts for a large proportion of the variability of the markets that we consider. We then characterize the time-evolving relationships between the different assets by investigating the correlations between the asset price time series and principal components. Using this approach, we uncover notable changes that occurred in financial markets and identify the assets that were significantly affected by these changes. We show in particular that there was an increase in the strength of the relationships between several different markets following the 2007--2008 credit and liquidity crisis.Comment: 15 pages, 10 figures, 1 table. Accepted for publication in Phys. Rev. E. v2 includes additional section

    Human Aspects in Digital Rights Management: the Perspective of Content Developers.

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    Legal norms and social behaviours are some of the human aspects surrounding the effectiveness and future of DRM security. Further exploration of these aspects would help unravel the complexities of the interaction between rights protection security and law. Most importantly, understanding the perspectives behind the circumvention of content security may have a significant impact on DRM effectiveness and acceptance at the same time. While there has been valuable research on consumer acceptability, (The INDICARE project, Bohle 2008, Akester 2009) there is hardly any work on the human perspective of content creators. Taking video games as a case study, this paper employs qualitative socio-legal analysis and an interdisciplinary approach to explore this particular aspect of content protection

    Human aspects of digital rights management: the perspective of content developers. [Conference Paper]

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    Legal norms and social behaviours are some of the human aspects surrounding the effectiveness and future of DRM security. Further exploration of these aspects would help unravel the complexities of the interaction between rights protection security and law. Most importantly, understanding the perspectives behind the circumvention of content security may have a significant impact on DRM effectiveness and acceptance at the same time. While there has been valuable research on consumer acceptability (The INDICARE project, Bohle 2008, Akester 2009), there is hardly any work on the human perspective of content creators. Taking video games as a case study, this paper employs qualitative socio-legal analysis and an interdisciplinary approach to explore this particular aspect of content protection

    Digital rights management: the four perspectives of developers, distributors, users and lawyers.

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    Digital Rights Management (DRM) refers to a collection of security mechanisms that are widely deployed on a number of copyright-protected digital assets. However, despite the existence of a number of studies of the technical architectures of rights management security systems, there is little scholarly/academic literature dedicated to the human aspects associated with circumvention of DRM security. Using videogames as a case study, this paper discusses how DRM is perceived differently depending on where one's stake in the use of DRM security lies. This paper concludes by proposing questions that could be used to aid content distributors and security practitioners in the creation of a fairer DRM framework
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