570 research outputs found

    Metal interactions and activities of truncated and extended hammerhead ribozyme constructs

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    The hammerhead ribozyme (HHRz) catalyzes a site-specific phosphodiester bond cleavage reaction that is enhanced by the presence of metal cations. Metal cations are thought to aid in the folding and possibly the catalytic mechanism of this ribozyme. The goal of this research is to characterize the activities and metal interactions of minimal and extended HHRz constructs using kinetic and spectroscopic studies. Metal binding to the cleavage site of the HHRz was probed using 31P NMR to monitor Cd2+ titrations of HHRzs with a phosphorothioate modification at the cleavage site. Either a 2'-F or a 2'-NH2 substitution at the nucleophile position was used to block cleavage. With a 2'-F, no metal binding to the cleavage site phosphate was observed. However, with a 2'-NH2 substitution, a large change in 31P chemical shift of the phosphorothioate peak suggests Cd2+ binding. A 2'-NH2 is a potential metal ligand, but a 2'-F is not. This suggests that a metal ion binds to the cleavage site phosphate when the 2' nucleophile position also provides a ligand. Minimal HHRzs with only one stem loop structure show little activity in presence of physiologically relevant concentrations of divalent cations. A kinetic and thermodynamic characterization of an extended HHRz derived from Schistosoma mansoni with loops in stems I and II was performed. High catalytic activity was observed with low concentrations of divalent cations, and loss of potential loop-loop interactions resulted in a large decrease in activity. An electrostatic surface plot of a HHRz crystal structure revealed an area of high negative electrostatic potential in the cleft between stems I and II with contributions from nucleotides U7, A6, and C17 of the HHRz that could serve to trap metal ions. To probe this putative metal site, kinetic studies of HHRz constructs with phosphorothioate substitutions 5' to U7 or C17 or with an A6 2'- OMe substitution were performed. Results of these studies suggest that a metal interaction at this site would include direct coordination to A6 2'-OH, but indirect interactions with the phosphates

    Moby, Minstrelsy and Melville

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    In 1999 Mute Records released Play by Moby. Daniel Miller has admitted that the label was not in ‘great shape’ at this point and nor was Moby’s career. The performer had had chart success in the UK with his 1991 single ‘Go’, which was released by the Mute sub-label Rhythm King. His left-turn turn from electronica to hardcore punk with Animal Rights (1996) was poorly received, however, confusing fans and record company alike. Play was therefore an unexpected triumph. By 2016, it had sold more than 12 million copies, making it the world’s highest-selling electronica album. For Miller, this turnaround was ‘like the cavalry coming over the hill’, safeguarding Mute for the twenty-first century. This chapter explores the phenomenon of Play but in a tangential manner. It traces three overlapping stories. It explores ‘Blackface’ minstrelsy, the most popular form of entertainment in the US from the mid-1840s until the end of the nineteenth century. It addresses the work of the author Herman Melville, whose quest was ‘the absolute amidst its relative manifestations [...] the delicate and shifting relationship between its truth and its illusion’. And it examines Moby and the music he recorded and sampled for Play. This album, through its use of sampling, bears hallmarks of minstrelsy. It also raises questions about truth and illusion

    The Concept of "Self" in Some Plays by Ibsen, Strindberg, Beckett, Osborne, and Pinter

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    PhDCentring on Peer Gynt's onion as a symbol of modern man's "dissolved" self, this thesis is a study of the changing concept of "self" and its effect on the development of dramatic technique from Ibsen's Brand and Peer Gynt, through Strindberg's "dream plays, " to the plays of the three most influential post-war British playwrights, Beckett, Osborne, and Pinter. The aim of this comparative study is not to "prove" direct influence, but to demonstrate affinities and to trace the continuing process of the "dissolving self" from Brand's monumental concept of man as a being essentially divine, to Beckett's tramps picturing themselves as worms in a God-forsaken universe, and from Peer Gynt's uncentred onion self, which still adds up to a tremendous personality, to Pinter's "classic female figure" who is divested of personality as well as of self. The philosophical dissolution of man's essential Godgiven self and the redefinition of the human personality in existentialist terms as simply the sum of one's actions, habits, or roles, has its corollary in dramatic technique, of which the most radical example is Strindberg's A Dream Play, where the Dreamer's self is projected on stage, not as one indelible personality, which is still the case in Peer Gynt, but as a motley gallery of "dream characters, " each representing one aspect of the Dreamer's (the poet's) discontinuous self. Beckett's Krapp, spooling back the tapes of his former selves in search of his quintessential "I" and discovering that the "self" is merely a string of discarded habits; Osborne's Archie Rice playing for time against the inevitable annihilation of his inauthentic comedian's mask by "the man with the hook"; and Pinter's stupefied Stanley Webber being "crowned" by his persecutors with a bowler hat, the symbol of conformity, and hence of non-identity, are all modern counterparts of Peer Gynt, the "Emperor of Self.

    It's written in the cloud: The hype and promise of cloud computing

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    Purpose of paper: This viewpoint discusses the emerging IT platform of Cloud Computing and discusses where and how this has developed in terms of the collision between internet and enterprise computing paradigms – and hence why cloud computing will be driven not by computing architectures but more fundamental ICT consumption behaviours. Design/methodology/approach: The approach has been based upon the discussion and recent developments of Software as a Service (SaaS) and associated ICT computing metaphors and is largely based upon the contemporary discussion at the moment of the impact of social, open source and configurable technology services. Findings: It is suggested that whilst cloud computing and SaaS are indeed innovations within ICT, the real innovation will come when such platforms allow new industries, sectors, ways of doing business, connecting with and engaging with people to emerge. Thus looking beyond the technology itself. Research limitations/applications: Author viewpoint only, not research based. Practical applications: Brings together some of the recent discussions within the popular as well as business and computing press on social networking, open source and utility computing. Social implications: Suggests that cloud computing can potentially transform and change the way in which IS and IT are accessed, consumed, configured and used in daily life. Originality / value of paper: Author viewpoint on a contemporary subject

    Inhibitors and Triggers of Discontinuous Innovation Development

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    Technology, Policy and Managemen

    Computational Complexity of Weighted Threshold Games

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    Weighted threshold games are coalitional games in which each player has a weight (intuitively corresponding to its voting power), and a coalition is successful if the sum of its weights exceeds a given threshold. Key questions in coalitional games include finding coalitions that are stable (in the sense that no member of the coalition has any rational incentive to leave it), and finding a division of payoffs to coalition members (an imputation) that is fair. We investigate the computational complexity of such questions for weighted threshold games. We study the core, the least core, and the nucleolus, distinguishing those problems that are polynomial-time computable from those that are NP-hard, and providing pseudopolynomial and approximation algorithms for the NP-hard problems

    mcbooki457p361: First Beaver County Chapter

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    FIRST BEAVER COUNTY CHAPTER On August 24, 1931, the first Beaver County Company of Daughters of Pioneers was organized with the follow-ing executives : Isabel B. Gillies, president ; Edith C. Wool-sey and Rosella M. Eyre, vice-presidents ; Alice G. White and Jennie T. Wood, secretary and treasurer. Following is a list of County excutives since the organization 1935-37 - Stella Burt, president; Mabel B. Colton and Eliza A. Gunn, vice-presidents ; Martha Beaumont, secretary. 1937-39 - Geneva P. Idol, president ; Mabel B. Colton and Stella Burt, vice-presidents; Jane C. Munford, secretary. 1939-41 - Geneva P. Idol, president ; Minnie Grif-fith and Alvaretta Robinson, vice-presidents ; Jane C. Munford, secretary. 1941-43 - Treva B. Griffiths, president ; Lottie Burke and Edith S. Osborn, vice-presidents ; Nettie White, secretary. 1943-45 - Lottie C. Burke, president ; Kate P. Bow-man and Edith S. Osborn, vice-presidents ; Nettie White, secretary. 1945-47 - Margery A. Mackerell, president; Edith S. Osborn and Metta H. White, vice-presidents ; Lottie R. Farrer, secretary ; Mary F. Goodwin, corresponding secretary ; Martha Barton, historian; Phylis S. Warr, treasurer ; Kate L. Jensen, registrar; Myrtle W. Burt, auditor ; Lucy M. Osborne, parliamentarian ; Amelia O. Paice, chaplain ; Eliza A. Gunn, custodian of relics ; Ruth Willden, organist. The four camps of Beaver were first organized September 7,1931, by dividing the town with Highway 91 north and south and by Tenth Street east and west, with a camp in each of the sections of the town, namely : northeast camp, "The Greenwood," named for William and Ann H. Greenwood, Utah pioneers of 1852; northwest camp, "The Belknap," named for the mountain in the Tusher Range; southeast camp, "The Nancy K.," named in honor of Nan

    Societal Response to Developmental Differences and Adolescent Substance Abuse Treatment Outcomes

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    Recent findings indicate an increased concern that conventional substance abuse treatment models consistently reflect less than satisfactory outcomes when applied to adolescents. This study investigates developmental differences among adolescents and adults as a possible cause of the disparity. The author conducted interviews with substance abuse professionals, developmental psychologists, adolescents in treatment, and adolescents no less than six months out of treatment. Questions focus on assessment agendas, developmental and motivational differences among adolescents and adults, movement along the addiction continuum, developmental tasks of adolescence, and adolescent receptivity. The results of the interviews among each group are compared and consistencies are noted. The implications of any correlation within the noted consistencies are discussed, as well as the implications for social work practice

    The Price of Democracy in Coalition Formation

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    Whenever rational agents form coalitions to execute tasks, doing so via a decentralized negotiation process—while more robust and democratic—may lead to a loss of efficiency compared to a centralized solution. To quantify this loss, we introduce the notion of the Price of Democracy (PoD), which measures the amount of resources needlessly committed to the task(s) at hand. After defining this concept for general coalitional games, we instantiate it in the setting of weighted voting games, a simple but expressive class of coalitional games that can be used to model resource allocation in multiagent scenarios. We approach the problem of forming winning coalitions in this setting from a non-cooperative perspective, and put forward an intuitive deterministic bargaining process, which exhibits no delay of agreement (i.e., the agents are guaranteed to form a winning coalition in round one) and allows for efficient computation of bargaining strategies. We show a tight bound of 3/2 on the PoD of our process if two rounds of bargaining are allowed, and demonstrate that this bound cannot improve with more rounds. We then generalize our bargaining process to settings where multiple coalitions are allowed to be formed, show that this generalization also exhibits no delay of agreement, and discuss the PoD in such settings
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