85 research outputs found

    Developing Modular Application Builders to Exploit MIMD Parallel Resources

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    Modular application builders (MABs), such as AVS and Iris Explorer[6, 7] are increasingly being used in the visualisation community. Such systems can already place compute intensive modules on supercomputers in order to utilise their power. This paper details two major projects at EPCC which attempted to fully integrate the MAB concept with a distributed memory MIMD (DM-MIMD) environment. The work presented was driven by two goals, efficient use of the resource and ease of use by programmer and end user. We present a model of MABs and describe the major problems faced, giving solutions to them through two case studies

    Beyond locutionary denotations: exploring trust between practitioners and policy

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    This study reports the findings of a research on the trust relationship between practitioners in the Skills for Life (SfL) area and the policy that informs their practice. The exploration of this relationship was premised on an extended notion of trust relationship which draws from the Speech Act theory of Austin (1962; Searle 1969; Kissine 2008), leading to the claim that the existence of different layers of imports in textual analysis makes it possible for a trust relationship to exist between the human/physical and the non human/non physical. The study found that the majority of practitioners in the SfL field trust policy to deliver its inherent policy only to a limited extent. Amongst others, the study identified the impact of the perlocutionary import of policy text on practitioners as a viable reason for this limited level of trust. Such perlocutionary imports, it also found, have adverse impact on practitioners who are considered to have drawn from previous experience to mediate the import of contemporary policies

    Cultural Predictors of Facial Ethnicity Preference in the Miskitu and Mestizos of Rural Nicaragua

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    Both basic visual experience and cultural associations with race and ethnicity may contribute to the extent observers do or do not favor some facial ethnicity cues over others. Given that visual media contain a highly biased selection of faces, with Whiteness both over-represented and strongly privileged in film and television, communities for whom visual media are relatively novel may experience an additional, pervasive source of attitudes to facial ethnicity markers. In the current research, we compared individuals of Mestizo and Miskitu identities living in communities on the Caribbean Coast of Nicaragua with, and without, regular access to television on their relative preference for facial stimuli manipulated to look more or less White (Black vs White, Black vs Mestizo, Mestizo vs White). Results showed that all communities showed an overall preference for images with lighter skin, although changes in facial shape did not affect preferences. Those who had attended more years of education preferred whiter faces than those with less education, and those who watched more television preferred whiter faces more only where color (rather than shape) had been manipulated. Results are discussed in terms of the broader relations around ethnicity, status, and technological transition in this area

    Cultural Predictors of Facial Ethnicity Preference in the Miskitu and Mestizos of Rural Nicaragua

    Get PDF
    Both basic visual experience and cultural associations with race and ethnicity may contribute to the extent observers do or do not favor some facial ethnicity cues over others. Given that visual media contain a highly biased selection of faces, with Whiteness both over-represented and strongly privileged in film and television, communities for whom visual media are relatively novel may experience an additional, pervasive source of attitudes to facial ethnicity markers. In the current research, we compared individuals of Mestizo and Miskitu identities living in communities on the Caribbean Coast of Nicaragua with, and without, regular access to television on their relative preference for facial stimuli manipulated to look more or less White (Black vs White, Black vs Mestizo, Mestizo vs White). Results showed that all communities showed an overall preference for images with lighter skin, although changes in facial shape did not affect preferences. Those who had attended more years of education preferred whiter faces than those with less education, and those who watched more television preferred whiter faces more only where color (rather than shape) had been manipulated. Results are discussed in terms of the broader relations around ethnicity, status, and technological transition in this area

    Identity Drift:The Multivocality of Ethical Identity in Islamic Financial Institution

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    In today’s neo-liberalist world, Islamic financial institutions (IFIs) face many difficulties combining contemporary financial thinking with Islamic, faith-based principles, on which their day-to-day operations ought to be based. Hence, IFI are likely to experience shifts/changes in organizational and ethical identity due to tensions that the combination of these principles invokes. We present an in-depth case study that focuses on these shifts in a major European based IFI across a 14-year period. We conceptualize identity change as drift, highlighting the multivocal nature of identity construction. The ethico-faith principles that were meant to serve as living codes of ethics guiding the IFI’s organizational culture, operational processes, and strategy formation turned out to mainly have been discursively rationalized to respond to regulatory, market and institutional imperatives. The company is aware that it needs to engage in a continuous dialogue with those who set these requirements. Its ethico-faith principles may consequently be adapted quite radically, especially in periods of turmoil and takeover, as we show across the analysed time period. The paper provides valuable insights for faith-inspired organizations to reflect on the extent to which they wish to engage in the discursive justification and legitimization of current market hegemonies, whilst they actively encourage their managers to behave ethically as well

    Characterization of genome-wide p53-binding sites upon stress response

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    The tumor suppressor p53 is a sequence-specific transcription factor, which regulates the expression of target genes involved in different stress responses. To understand p53's essential transcriptional functions, unbiased analysis of its DNA-binding repertoire is pivotal. In a genome-wide tiling ChIP-on-chip approach, we have identified and characterized 1546 binding sites of p53 upon Actinomycin D treatment. Among those binding sites were known as well as novel p53 target sites, which included regulatory regions of potentially novel transcripts. Using this collection of genome-wide binding sites, a new high-confidence algorithm was developed, p53scan, to identify the p53 consensus-binding motif. Strikingly, this motif was present in the majority of all bound sequences with 83% of all binding sites containing the motif. In the surrounding sequences of the binding sites, several motifs for potential regulatory cobinders were identified. Finally, we show that the majority of the genome-wide p53 target sites can also be bound by overexpressed p63 and p73 in vivo, suggesting that they can possibly play an important role at p53 binding sites. This emphasizes the possible interplay of p53 and its family members in the context of target gene binding. Our study greatly expands the known, experimentally validated p53 binding site repertoire and serves as a valuable knowledgebase for future research

    Second Order Perturbations in the Randall-Sundrum Infinite Brane-World Model

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    We discuss the non-linear gravitational interactions in the Randall-Sundrum single brane model. If we naively write down the 4-dimensional effective action integrating over the fifth dimension with the aid of the decomposition with respect to eigen modes of 4-dimensional d'Alembertian, the Kaluza-Klein mode coupling seems to be ill-defined. We carefully analyze second order perturbations of the gravitational field induced on the 3-brane under the assumption of the static and axial-symmetric 5-dimensional metric. It is shown that there remains no pathological feature in the Kaluza-Klein mode coupling after the summation over all different mass modes. Furthermore, the leading Kaluza-Klein corrections are shown to be sufficiently suppressed in comparison with the leading order term which is obtained by the zero mode truncation. We confirm that the 4-dimensional Einstein gravity is approximately recovered on the 3-brane up to second order perturbations.Comment: 15 pages, 2 figures, comment and reference added, typos correcte

    Lysine120 Interactions with p53 Response Elements can Allosterically Direct p53 Organization

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    p53 can serve as a paradigm in studies aiming to figure out how allosteric perturbations in transcription factors (TFs) triggered by small changes in DNA response element (RE) sequences, can spell selectivity in co-factor recruitment. p53-REs are 20-base pair (bp) DNA segments specifying diverse functions. They may be located near the transcription start sites or thousands of bps away in the genome. Their number has been estimated to be in the thousands, and they all share a common motif. A key question is then how does the p53 protein recognize a particular p53-RE sequence among all the similar ones? Here, representative p53-REs regulating diverse functions including cell cycle arrest, DNA repair, and apoptosis were simulated in explicit solvent. Among the major interactions between p53 and its REs involving Lys120, Arg280 and Arg248, the bps interacting with Lys120 vary while the interacting partners of other residues are less so. We observe that each p53-RE quarter site sequence has a unique pattern of interactions with p53 Lys120. The allosteric, DNA sequence-induced conformational and dynamic changes of the altered Lys120 interactions are amplified by the perturbation of other p53-DNA interactions. The combined subtle RE sequence-specific allosteric effects propagate in the p53 and in the DNA. The resulting amplified allosteric effects far away are reflected in changes in the overall p53 organization and in the p53 surface topology and residue fluctuations which play key roles in selective co-factor recruitment. As such, these observations suggest how similar p53-RE sequences can spell the preferred co-factor binding, which is the key to the selective gene transactivation and consequently different functional effects

    Noncanonical DNA Motifs as Transactivation Targets by Wild Type and Mutant p53

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    Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0–13 nucleotides (nt), originally defined by the consensus RRRCWWGYYY (nβ€Š=β€Š0–13) RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs) by wild type (WT) and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi–in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical Β½-(a single decamer) and ΒΎ-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of Β½- and ΒΎ-site REs greatly expands the p53 master regulatory network
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