72 research outputs found

    Developing Creativity: Artificial Barriers in Artificial Intelligence

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    The greatest rhetorical challenge to developers of creative artificial intelligence systems is convincingly arguing that their software is more than just an extension of their own creativity. This paper suggests that “creative autonomy,” which exists when a system not only evaluates creations on its own, but also changes its standards without explicit direction, is a necessary condition for making this argument. Rather than requiring that the system be hermetically sealed to avoid perceptions of human influence, developing creative autonomy is argued to be more plausible if the system is intimately embedded in a broader society of other creators and critics. Ideas are presented for constructing systems that might be able to achieve creative autonomy

    Development of Peptidomimetics Targeting IAPs

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    Inhibitor of apoptosis proteins (IAPs) such as XIAP subvert apoptosis by binding and inhibiting caspases. Because occupation of the XIAP BIR3 peptide binding pocket by Smac abolishes the XIAP–caspase 9 interaction, it is a proapoptotic event of great therapeutic interest. An assay for pocket binding was developed based on the displacement of Smac 7-mer from BIR3. Through the physical and biochemical analysis of a variety of peptides, we have determined the minimum sequence required for inhibition of the Smac–BIR3 interaction and detailed the dimensions and topology of the BIR3 peptide binding pocket. This work describes the structure–activity relationship (SAR) for peptide inhibitors of Smac-IAP binding

    Reverse-Phase Phosphoproteome Analysis of Signaling Pathways Induced by Rift Valley Fever Virus in Human Small Airway Epithelial Cells

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    Rift valley fever virus (RVFV) infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK) and downstream transcriptional factors [STAT1 (Y701), ATF2 (T69/71), MSK1 (S360) and CREB (S133)]. NF-ÎșB phosphorylation was also increased. Activation of p53 (S15, S46) correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473), along with phosphorylation of FOX 01/03 (T24/31) which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication

    New technologies for examining neuronal ensembles in drug addiction and fear

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    Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear

    Creating creativity: reflections from fieldwork

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    The present article addresses the question of ‘When can we say something is creative?’ and, in answering it, takes a critical stand towards past and present scientific definitions of creativity. It challenges an implicit assumption in much psychological theory and research that creativity exists as an ‘objective’ feature of persons or products, universally recognised and independent of social agreement and cultural systems of norms and beliefs. Focusing on everyday life creative outcomes, the article includes both theoretical accounts and empirical examples from a research exploring creativity evaluations in the context of folk art. In the end, a multi-layered perspective of creativity assessment emerges, integrating dimensions such as newness and originality, value and usefulness, subjective reception and cultural reception of creative products. Implications for how we understand and study creativity are discussed
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