2,336 research outputs found

    Maneuvering in a Large Organization (Case Study)

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    PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells

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    Chemoattractants such as formyl-Met-Leu-Phe (fMLP) induce neutrophils to polarize by triggering divergent pathways that promote formation of a protrusive front and contracting back and sides. RhoA, a Rho GTPase, stimulates assembly of actomyosin contractile complexes at the sides and back. We show here, in differentiated HL60 cells, that PDZRhoGEF (PRG), a guanine nucleotide exchange factor (GEF) for RhoA, mediates RhoA-dependent responses and determines their spatial distribution. As with RNAi knock-down of PRG, a GEF-deleted PRG mutant blocks fMLP-dependent RhoA activation and causes neutrophils to exhibit multiple fronts and long tails. Similarly, inhibition of RhoA, a Rho-dependent protein kinase (ROCK), or myosin II produces the same morphologies. PRG inhibition reduces or mislocalizes monophosphorylated myosin light chains in fMLP-stimulated cells, and myosin II ATPase inhibition reciprocally disrupts normal localization of PRG. We propose a cooperative reinforcing mechanism at the back of cells, in which PRG, RhoA, ROCK, myosin II, and actomyosin spatially cooperate to consolidate attractant-induced contractility and ensure robust cell polarity

    Empathetic encounters of children’s augmented storying across the human and more-than-human worlds

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    This study brings empathy to the centre of literacy practice by investigating children's augmented storying as it was related to empathetic encounters across the human and more-than-human worlds. The study applies sociomaterial theorising that defines empathy as relational and emergent across human-material-spatial-temporal assemblages. The empirical study was situated in a Finnish primary school in which children used an augmented story-crafting tool (MyAR Julle) to explore their local environment and to create and share their stories. The findings show how empathy emerged situationally across the children, other human beings, materials, technology and the natural world. The empathetic encounters of the children's narratives were more than romantic or smooth encounters, instead competing and in tension with one another, calling moral reasoning and agency. The study shows the potential of sociomaterial theorising to change the way we think about children's encounters with the world, using empathy as a framework.Peer reviewe

    Cluster building by policy design: a sociotechnical constituency study of information communication technology (ICT) industries in Scotland and Hong Kong

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    This thesis investigates whether and how public policies can help build industrial clusters. The research applies a case study method based on 60 interviews to the emerging information communication technology (ICT) clusters in Scotland and Hong Kong. The analysis uses Molina’s sociotechnical constituency (STC) framework and its associated ‘diamond of alignment’, which help focus on two interrelated dimensions: 1) the complex technical and social aspects of the design, implementation and evolution of the Scottish and Hong Kong ICT clusters and 2) the difficulties of developing a cluster in the context of major diversity of organisational interests and patterns of interaction. This research revealed that the cluster building effort in the two regions has been fraught with difficulties due to misalignment between the perceptions and pursuits of policy makers and the interests of industry members. This thesis concludes that cluster building is an evolutionary process of sociotechnical alignment which can be facilitated by feedback and learning. It also suggests that for successful cluster building to take place, policy makers should focus on stimulating the processes of cluster formation, including the building up of the technological capabilities of the industrial actors, while facilitating the integration of the major actors’ interests and demands with the policy programmes. Cluster building involves the development of new ways of thinking as well as the practice of networking; it necessitates the coherent effort of collective learning and a long-term commitment to change the existing technological system. A long-term adaptive policy programme should be pursued to focus on effectively aligning the interests and pursuits of the different actors in the cluster at various stages

    Information-based methods for predicting gene function from systematic gene knock-downs

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    <p>Abstract</p> <p>Background</p> <p>The rapid annotation of genes on a genome-wide scale is now possible for several organisms using high-throughput RNA interference assays to knock down the expression of a specific gene. To date, dozens of RNA interference phenotypes have been recorded for the nematode <it>Caenorhabditis elegans</it>. Although previous studies have demonstrated the merit of using knock-down phenotypes to predict gene function, it is unclear how the data can be used most effectively. An open question is how to optimally make use of phenotypic observations, possibly in combination with other functional genomics datasets, to identify genes that share a common role.</p> <p>Results</p> <p>We compared several methods for detecting gene-gene functional similarity from phenotypic knock-down profiles. We found that information-based measures, which explicitly incorporate a phenotype's genomic frequency when calculating gene-gene similarity, outperform non-information-based methods. We report the presence of newly predicted modules identified from an integrated functional network containing phenotypic congruency links derived from an information-based measure. One such module is a set of genes predicted to play a role in regulating body morphology based on their multiply-supported interactions with members of the TGF-<it>β </it>signaling pathway.</p> <p>Conclusion</p> <p>Information-based metrics significantly improve the comparison of phenotypic knock-down profiles, based upon their ability to enhance gene function prediction and identify novel functional modules.</p

    Non-Contact Thrust Stand Calibration Method for Repetitively-Pulsed Electric Thrusters

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    A thrust stand calibration technique for use in testing repetitively-pulsed electric thrusters for in-space propulsion has been developed and tested using a modified hanging pendulum thrust stand. In the implementation of this technique, current pulses are applied to a solenoidal coil to produce a pulsed magnetic field that acts against the magnetic field produced by a permanent magnet mounted to the thrust stand pendulum arm. The force on the magnet is applied in this non-contact manner, with the entire pulsed force transferred to the pendulum arm through a piezoelectric force transducer to provide a time-accurate force measurement. Modeling of the pendulum arm dynamics reveals that after an initial transient in thrust stand motion the quasisteady average deflection of the thrust stand arm away from the unforced or zero position can be related to the average applied force through a simple linear Hooke s law relationship. Modeling demonstrates that this technique is universally applicable except when the pulsing period is increased to the point where it approaches the period of natural thrust stand motion. Calibration data were obtained using a modified hanging pendulum thrust stand previously used for steady-state thrust measurements. Data were obtained for varying impulse bit at constant pulse frequency and for varying pulse frequency. The two data sets exhibit excellent quantitative agreement with each other as the constant relating average deflection and average thrust match within the errors on the linear regression curve fit of the data. Quantitatively, the error on the calibration coefficient is roughly 1% of the coefficient value
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