24,646 research outputs found

    The major transcriptional regulatory protein of herpes simplex virus type 1 includes a protease resistant DNA binding domain

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    Herpes simplex virus type 1 expresses five immediateearly (IE) polypeptides. In the absence of functional Vmw175 (the product of IE gene 3) activation of transcription of later classes of viral genes and repression of IE gene expression does not occur. The recognition of specific DNA sequences by Vmw175 requires, as determined by sensitivity to mutation, a part of the protein highly conserved in the corresponding proteins of related herpes viruses. However, mutations in other parts of the protein can also disrupt specific DNA binding. This paper shows that the DNA binding domain of Vmw175 can be liberated as a functional unit by digestion with proteinase K. Analysis of mutant Vmw175 proteinsshowed that the proteinase K resistant domain has an amino terminus between amino acid residues 229 and 292, while its carboxy terminus is between residues 495 and 518. Mutations outside this region which affect DNA binding by the intact protein do not eliminate binding of the proteinase K resistant domain. This implies that direct DNA binding by Vmw175 involves a linear subsection of the polypeptide, and that mutations in other parts of the polypeptide which affect DNA binding of the whole protein do so by indirect means

    Virtual audio reproduced in a headrest

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    When virtual audio reproduction is simultaneously required in many seats, such as in aircraft or cinemas, it may be convenient to use loudspeakers mounted inside each seat's headrest. In this preliminary study, the feasibility of virtual audio reproduction in the headrest of a single seat is explored using an inversion technique to compensate for crosstalk and the synthesis of head related transfer functions. Although large changes in the magnitude of the signals reproduced at the listener's ears are observed as the listener moves their head within the headrest, informal listening tests indicate that the reproduced acoustic images are surprisingly stable in about an eighth of an arc either side of the loudspeaker positions. Not surprisingly, frontal images are more difficult to reproduce with headrest loudspeakers

    Sensitivity of the mussel Mytilus edulis to substrate‑borne vibration in relation to anthropogenically generated noise

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    © 2015 Inter-Research. Many anthropogenic activities in the oceans involve direct contact with the seabed (for example pile driving), creating radiating particle motion waves. However, the consequences of these waveforms to marine organisms are largely unknown and there is little information on the ability of invertebrates to detect vibration, or indeed the acoustic component of the signal. We quantified sensitivity of the marine bivalve Mytilus edulis to substrate-borne vibration by exposure to vibration under controlled conditions. Sinusoidal excitation by tonal signals at frequencies within the range 5 to 410 Hz was applied during the tests, using the 'staircase' method of threshold determination. Thresholds were related to mussel size and to seabed vibration data produced by anthropogenic activities. Clear behavioural changes were observed in response to the vibration stimulus. Thresholds ranged from 0.06 to 0.55 m s -2 (acceleration, root mean squared), with valve closure used as the behavioural indicator of reception and response. Thresholds were shown to be within the range of vibrations measured in the vicinity of anthropogenic operations such as pile driving and blasting. The responses show that vibration is likely to impact the overall fitness of both individuals and mussel beds of M. edulis due to disruption of natural valve periodicity, which may have ecosystem and commercial implications. The observed data provide a valuable first step to understanding the impacts of such vibration upon a key coastal and estuarine invertebrate which lives near industrial and construction activity, and illustrate that the role of seabed vibration should not be underestimated when assessing the impacts of noise pollution

    Reducing inappropriate antibiotics prescribing: The role of online commentary on physical examination findings

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    Objective: This study investigates the relationship of ‘online commentary’(contemporaneous physician comments about physical examination [PE] findings) with (i) parent questioning of the treatment recommendation and (ii) inappropriate antibiotic prescribing. Methods: A nested cross-sectional study of 522 encounters motivated by upper respiratory symptoms in 27 California pediatric practices (38 pediatricians). Physicians completed a post-visit survey regarding physical examination findings, diagnosis, treatment, and whether they perceived the parent as expecting an antibiotic. Taped encounters were coded for ‘problem’ online commentary (PE findings discussed as significant or clearly abnormal) and ‘no problem’ online commentary (PE findings discussed reassuringly as normal or insignificant). Results: Online commentary during the PE occurred in 73% of visits with viral diagnoses (n = 261). Compared to similar cases with ‘no problem’ online commentary, ‘problem’ comments were associated with a 13% greater probability of parents uestioning a non-antibiotic treatment plan (95% CI 0-26%, p = .05,) and a 27% (95% CI: 2-52%, p < .05) greater probability of an inappropriate antibiotic prescription. Conclusion: With viral illnesses, problematic online comments are associated with more pediatrician-parent conflict over non-antibiotic treatment recommendations. This may increase inappropriate antibiotic prescribing. Practice implications: In viral cases, physicians should consider avoiding the use of problematic online commentary

    Modelling cell motility and chemotaxis with evolving surface finite elements

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    We present a mathematical and a computational framework for the modelling of cell motility. The cell membrane is represented by an evolving surface, with the movement of the cell determined by the interaction of various forces that act normal to the surface. We consider external forces such as those that may arise owing to inhomogeneities in the medium and a pressure that constrains the enclosed volume, as well as internal forces that arise from the reaction of the cells' surface to stretching and bending. We also consider a protrusive force associated with a reaction-diffusion system (RDS) posed on the cell membrane, with cell polarization modelled by this surface RDS. The computational method is based on an evolving surface finite-element method. The general method can account for the large deformations that arise in cell motility and allows the simulation of cell migration in three dimensions. We illustrate applications of the proposed modelling framework and numerical method by reporting on numerical simulations of a model for eukaryotic chemotaxis and a model for the persistent movement of keratocytes in two and three space dimensions. Movies of the simulated cells can be obtained from http://homepages.warwick.ac.uk/maskae/CV_Warwick/Chemotaxis.html

    Living with the user: Design drama for dementia care through responsive scripted experiences in the home

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    Participation in forms of drama and narrative can provoke empathy and creativity in user-centred design processes. In this paper, we expand upon existing methods to explore the potential for responsive scripted experiences that are delivered through the combination of sensors and output devices placed in a home. The approach is being developed in the context of Dementia care, where the capacity for rich user participation in design activities is limited. In this case, a system can act as a proxy for a person with Dementia, allowing designers to gain experiences and insight as to what it is like to provide care for, and live with, this person. We describe the rationale behind the approach, a prototype system architecture, and our current work to explore the creation of scripted experiences for design, played out though UbiComp technologies.This research is funded by the Arts and Humanities Research Council UK, (AH/K00266X/1) and Horizon Digital Economy Research (RCUK grant EP/G065802/1)

    Using cultural probes to inform the design of assistive technologies

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    This paper discusses the practical implications of applying cultural probes to drive the design of assistive technologies. Specifically we describe a study in which a probe was deployed with home-based carers of people with dementia in order to capture critical data and gain insights of integrating the technologies into this sensitive and socially complex design space. To represent and utilise the insights gained from the cultural probes, we created narratives based on the probe data to enhance the design of assistive technologies.This work was supported by the Arts and Humanities Research Council (AH/K00266X/1) and RCUK through the Horizon Digital Economy Research grant (EP/G065802/1)
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