978 resultados para Lemery, Nicolas, 1645-1715


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China’s biggest search engine has a constitutional right to filter its search results, a US court found last month. But that’s just the start of the story. Eight New York-based pro-democracy activists sued Baidu Inc in 2011, seeking damages because Baidu prevents their work from showing up in search results. Baidu follows Chinese law that requires it to censor politically sensitive results. But in what the plaintiffs’ lawyer has dubbed a “perfect paradox”, US District Judge Jesse Furman has dismissed the challenge, explaining that to hold Baidu liable for its decisions to censor pro-democracy content would itself infringe the right to free speech.

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The Arabidopsis (Arabidopsis thaliana) orthologs of Brca2, a protein whose mutations are involved in breast cancer in humans, were previously shown to be essential at meiosis. In an attempt to better understand the Brca2-interacting properties, we examined four partners of the two isoforms of Brca2 identified in Arabidopsis (AtRad51, AtDmc1, and two AtDss1 isoforms). The two Brca2 and the two Dss1 isoforms are named AtBrca2(IV), AtBrca2(V), AtDss1(I), and AtDss1(V) after their chromosomal localization. We first show that both AtBrca2 proteins can interact with either AtRad51 or AtDmc1 in vitro, and that the N-terminal region of AtBrca2 is responsible for these interactions. More specifically, the BRC motifs (so called because iterated in the Brca2 protein) in Brca2 are involved in these interactions: BRC motif number 2 (BRC2) alone can interact with AtDmc1, whereas BRC motif number 4 (BRC4) recognizes AtRad51. The human Rad51 and Dmc1 proteins themselves can interact with either the complete (HsRad51) or a shorter version of AtBrca2 (HsRad51 or HsDmc1) that comprises all four BRC motifs. We also identified two Arabidopsis isoforms of Dss1, another known partner of Brca2 in other organisms. Although all four Brca2 and Dss1 proteins are much conserved, AtBrca2(IV) interacts with only one of these AtDss1 proteins, whereas AtBrca2(V) interacts with both of them. Finally, we show for the first time that an AtBrca2 protein could bind two different partners at the same time: AtRad51 and AtDss1(I), or AtDmc1 and AtDss1(I).

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The SOS screen, as originally described by Perkins et al. (1999), was setup with the aim of identifying Arabidopsis functions that might potentially be involved in the DNA metabolism. Such functions, when expressed in bacteria, are prone to disturb replication and thus trigger the SOS response. Consistently, expression of AtRAD51 and AtDMC1 induced the SOS response in bacteria, even affecting E. coli viability. 100 SOS-inducing cDNAs were isolated from a cDNA library constructed from an Arabidopsis cell suspension that was found to highly express meiotic genes. A large proportion of these SOS+ candidates are clearly related to the DNA metabolism, others could be involved in the RNA metabolism, while the remaining cDNAs encode either totally unknown proteins or proteins that were considered as irrelevant. Seven SOS+ candidate genes are induced following gamma irradiation. The in planta function of several of the SOS-inducing clones was investigated using T-DNA insertional mutants or RNA interference. Only one SOS+ candidate, among those examined, exhibited a defined phenotype: silenced plants for DUT1 were sensitive to 5-fluoro-uracil (5FU), as is the case of the leaky dut-1 mutant in E. coli that are affected in dUTPase activity. dUTPase is essential to prevent uracil incorporation in the course of DNA replication.

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The BRC repeat is a structural motif in the tumor suppressor BRCA2 (breast cancer type 2 susceptibility protein), which promotes homologous recombination (HR) by regulating RAD51 recombinase activity. To date, the BRC repeat has not been observed in other proteins, so that its role in HR is inferred only in the context of BRCA2. Here, we identified a BRC repeat variant, named BRCv, in the RECQL5 helicase, which possesses anti-recombinase activity in vitro and suppresses HR and promotes cellular resistance to camptothecin-induced replication stress in vivo. RECQL5-BRCv interacted with RAD51 through two conserved motifs similar to those in the BRCA2-BRC repeat. Mutations of either motif compromised functions of RECQL5, including association with RAD51, inhibition of RAD51-mediated D-loop formation, suppression of sister chromatid exchange, and resistance to camptothecin-induced replication stress. Potential BRCvs were also found in other HR regulatory proteins, including Srs2 and Sgs1, which possess anti-recombinase activities similar to that of RECQL5. A point mutation in the predicted Srs2-BRCv disrupted the ability of the protein to bind RAD51 and to inhibit D-loop formation. Thus, BRC is a common RAD51 interaction module that can be utilized by different proteins to either promote HR, as in the case of BRCA2, or to suppress HR, as in RECQL5.

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Several recently proposed ciphers, for example Rijndael and Serpent, are built with layers of small S-boxes interconnected by linear key-dependent layers. Their security relies on the fact, that the classical methods of cryptanalysis (e.g. linear or differential attacks) are based on probabilistic characteristics, which makes their security grow exponentially with the number of rounds N r r. In this paper we study the security of such ciphers under an additional hypothesis: the S-box can be described by an overdefined system of algebraic equations (true with probability 1). We show that this is true for both Serpent (due to a small size of S-boxes) and Rijndael (due to unexpected algebraic properties). We study general methods known for solving overdefined systems of equations, such as XL from Eurocrypt’00, and show their inefficiency. Then we introduce a new method called XSL that uses the sparsity of the equations and their specific structure. The XSL attack uses only relations true with probability 1, and thus the security does not have to grow exponentially in the number of rounds. XSL has a parameter P, and from our estimations is seems that P should be a constant or grow very slowly with the number of rounds. The XSL attack would then be polynomial (or subexponential) in N r> , with a huge constant that is double-exponential in the size of the S-box. The exact complexity of such attacks is not known due to the redundant equations. Though the presented version of the XSL attack always gives always more than the exhaustive search for Rijndael, it seems to (marginally) break 256-bit Serpent. We suggest a new criterion for design of S-boxes in block ciphers: they should not be describable by a system of polynomial equations that is too small or too overdefined.

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An estimated 285 million people worldwide are visually impaired. Some 90% of those live in developing nations, where less than 1% of the world’s books are available in a form they can read. In developed countries, the situation is only marginally better: only around 7% of the world’s books are accessible to print-disabled people. The right to read is part of our basic human rights. Access to the written word is crucial to allow people to fully participate in society. It’s important for education, political involvement, success in the workplace, scientific progress and, not least, creative play and leisure. Equal access to books and other cultural goods is also required by international law. The technology now exists to deliver books in accessible electronic forms to people much more cheaply than printing and shipping bulky braille copies or books on tape. Electronic books can be read with screen readers and refreshable braille devices, or printed into large print or braille if needed. Now that we have this technology, what’s been referred to as the global “book famine” is a preventable tragedy.

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Vertical line extensions, both step-up and step-down, are common occurrence in consumer products. For example, Timex recently launched its luxury high-end Valentino line. On the other hand, many companies use downscale extensions to increase the overall sales volume. For instance, a number of luxury watch brands recently introduced watch collections with lower price points, like TAG Heur’s affordable watch the Aquaracer Calibre 5. Previous literature on vertical extensions has investigated how number of products in the line (Dacin and Smith 1994), the direction of the extension, brand concept (Kim, Lavack, and Smith 2001), and perceived risk (Lei, de Ruyter, and Wetzels 2008) affect extensions’ evaluation. Common to this literature is the use of models based on adaptation-level theory, which states that all relevant price information is integrated into a single prototype value and used in consumer judgments of price (Helson 1947; Mazumdar, Raj, and Sinha 2005). In the current research we argue that, while adaptation-level theory can be viewed as a useful simplification to understanding consumers’ evaluations, it misses out important contextual influences caused by a brand’s price range. Drawing on research on range-frequency theory (Mellers and Cooke 1994; Parducci 1965) we investigate the effects of price point distance and parent brand’s price range on evaluations of vertical extensions. Our reasoning leads to two important predictions that we test in a series of three experiments...

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It is often said that Australia is a world leader in rates of copyright infringement for entertainment goods. In 2012, the hit television show, Game of Thrones, was the most downloaded television show over bitorrent, and estimates suggest that Australians accounted for a plurality of nearly 10% of the 3-4 million downloads each week. The season finale of 2013 was downloaded over a million times within 24 hours of its release, and again Australians were the largest block of illicit downloaders over BitTorrent, despite our relatively small population. This trend has led the former US Ambassador to Australia to implore Australians to stop 'stealing' digital content, and rightsholders to push for increasing sanctions on copyright infringers. The Australian Government is looking to respond by requiring Internet Service Providers to issue warnings and potentially punish consumers who are alleged by industry groups to have infringed copyright. This is the logical next step in deterring infringement, given that the operators of infringing networks (like The Pirate Bay, for example) are out of regulatory reach. This steady ratcheting up of the strength of copyright, however, comes at a significant cost to user privacy and autonomy, and while the decentralisation of enforcement reduces costs, it also reduces the due process safeguards provided by the judicial process. This article presents qualitative evidence that substantiates a common intuition: one of the major reasons that Australians seek out illicit downloads of content like Game of Thrones in such numbers is that it is more difficult to access legitimately in Australia. The geographically segmented way in which copyright is exploited at an international level has given rise to a ‘tyranny of digital distance’, where Australians have less access to copyright goods than consumers in other countries. Compared to consumers in the US and the EU, Australians pay more for digital goods, have less choice in distribution channels, are exposed to substantial delays in access, and are sometimes denied access completely. In this article we focus our analysis on premium film and television offerings, like Game of Thrones, and through semi-structured interviews, explore how choices in distribution impact on the willingness of Australian consumers to seek out infringing copies of copyright material. Game of Thrones provides an excellent case study through which to frame this analysis: it is both one of the least legally accessible television offerings and one of the most downloaded through filesharing networks of recent times. Our analysis shows that at the same time as rightsholder groups, particularly in the film and television industries, are lobbying for stronger laws to counter illicit distribution, the business practices of their member organisations are counter-productively increasing incentives for consumers to infringe. The lack of accessibility and high prices of copyright goods in Australia leads to substantial economic waste. The unmet consumer demand means that Australian consumers are harmed by lower access to information and entertainment goods than consumers in other jurisdictions. The higher rates of infringement that fulfils some of this unmet demand increases enforcement costs for copyright owners and imposes burdens either on our judicial system or on private entities – like ISPs – who may be tasked with enforcing the rights of third parties. Most worryingly, the lack of convenient and cheap legitimate digital distribution channels risks undermining public support for copyright law. Our research shows that consumers blame rightsholders for failing to meet market demand, and this encourages a social norm that infringing copyright, while illegal, is not morally wrongful. The implications are as simple as they are profound: Australia should not take steps to increase the strength of copyright law at this time. The interests of the public and those of rightsholders align better when there is effective competition in distribution channels and consumers can legitimately get access to content. While foreign rightsholders are seeking enhanced protection for their interests, increasing enforcement is likely to increase their ability to engage in lucrative geographical price-discrimination, particularly for premium content. This is only likely to increase the degree to which Australian consumers feel that their interests are not being met and, consequently, to further undermine the legitimacy of copyright law. If consumers are to respect copyright law, increasing sanctions for infringement without enhancing access and competition in legitimate distribution channels could be dangerously counter-productive. We suggest that rightsholders’ best strategy for addressing infringement in Australia at this time is to ensure that Australians can access copyright goods in a timely, affordable, convenient, and fair lawful manner.

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In the years since Nicolas Bourriaud’s Relational Aesthetics (1998) was published, a plethora of books (Shannon Jackson’s Social Works: Performing Art, Supporting Publics [2011], Nato Thompson’s Living as Form: Socially Engaged Art from 1991–2011 [2011], Grant Kester’s Conversation Pieces: Community and Communication in Modern Art [2004], Pablo Helguera’s Education for Socially Engaged Art: A Material and Techniques Handbook [2011]), conferences and articles have surfaced creating a rich and textured discourse that has responded to, critiqued and reconfigured the proposed social utopias of Bourriaud’s aesthetics. As a touchstone for this emerging discourse, Relational Aesthetics outlines in a contemporary context the plethora of social and process-based art forms that took as their medium the ‘social’. It is, however, Clare Bishop’s book Artificial Hells: Participatory Art and the Politics of Spectatorship (Verso), that offers a deeper art historical and theoretically considered rendering of this growing and complicated form of art, and forms a central body of work in this broad constellation of writings about participatory art, or social practice art/socially engaged art (SEA), as it is now commonly known...

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Background The level of plasma-derived naturally circulating anti-glycan antibodies (AGA) to P1 trisaccharide has previously been shown to significantly discriminate between ovarian cancer patients and healthy women. Here we aim to identify the Ig class that causes this discrimination, to identify on cancer cells the corresponding P1 antigen recognised by circulating anti-P1 antibodies and to shed light into the possible function of this glycosphingolipid. Method An independent Australian cohort was assessed for the presence of anti-P1 IgG and IgM class antibodies using suspension array. Monoclonal and human derived anti-glycan antibodies were verified using three independent glycan-based immunoassays and flow cytometry-based inhibition assay. The P1 antigen was detected by LC-MS/MS and flow cytometry. FACS-sorted cell lines were studied on the cellular migration by colorimetric assay and real-time measurement using xCELLigence system. Results Here we show in a second independent cohort (n=155) that the discrimination of cancer patients is mediated by the IgM class of anti-P1 antibodies (P=0.0002). The presence of corresponding antigen P1 and structurally related epitopes in fresh tissue specimens and cultured cancer cells is demonstrated. We further link the antibody and antigen (P1) by showing that human naturally circulating and affinity-purified anti-P1 IgM isolated from patients ascites can bind to naturally expressed P1 on the cell surface of ovarian cancer cells. Cell-sorted IGROV1 was used to obtain two study subpopulations (P1-high, 66.1%; and P1-low, 33.3%) and observed that cells expressing high P1-levels migrate significantly faster than those with low P1-levels. Conclusions This is the first report showing that P1 antigen, known to be expressed on erythrocytes only, is also present on ovarian cancer cells. This suggests that P1 is a novel tumour-associated carbohydrate antigen recognised by the immune system in patients and may have a role in cell migration. The clinical value of our data may be both diagnostic and prognostic; patients with low anti-P1 IgM antibodies present with a more aggressive phenotype and earlier relapse.

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Millions of people with print disabilities are denied the right to read. While some important efforts have been made to convert standard books to accessible formats and create accessible repositories, these have so far only addressed this crisis in an ad hoc way. This article argues that universally designed ebook libraries have the potential of substantially enabling persons with print disabilities. As a case study of what is possible, we analyse 12 academic ebook libraries to map their levels of accessibility. The positive results from this study indicate that universally designed ebooks are more than possible; they exist. While results are positive, however, we also found that most ebook libraries have some features that frustrate full accessibility, and some ebook libraries present critical barriers for people with disabilities. Based on these findings, we consider that some combination of private pressure and public law is both possible and necessary to advance the right-to-read cause. With access improving and recent advances in international law, now is the time to push for universal design and equality.

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Governments around the world want to know a lot about who we are and what we’re doing online and they want communications companies to help them find it. We don’t know a lot about when companies hand over this data, but we do know that it’s becoming increasingly common.

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Attorney-General George Brandis is at loggerheads with Communications Minister Malcolm Turnbull over proposed reforms to the Copyright Act. Brandis wants ISPs to take more responsibility for copyright infringement by their users. Turnbull says that they shouldn’t be required to police their subscribers’ activities. Here’s how to understand what’s at stake in the debate.

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The latest case of a popular YouTube blogger being sued for using music by other artists in her videos without permission raises the question of who really benefits from the re-use of music. In a claim filed this month, the electronic dance music label Ultra Records allege that beauty blogger Michelle Phan’s videos infringe their copyrights in nearly 50 cases. Phan is a self-made internet star who began posting makeup and self-help tutorials on YouTube in 2007. She has more than 6.7 million subscribers on her YouTube channel and has made a career from the associated advertising and endorsement revenue, book deal and even her own line of makeup.