Vpu Antagonizes BST-2–Mediated Restriction of HIV-1 Release via β-TrCP and Endo-Lysosomal Trafficking

The interferon-induced transmembrane protein BST-2/CD317 (tetherin) restricts the release of diverse enveloped viruses from infected cells. The HIV-1 accessory protein Vpu antagonizes this restriction by an unknown mechanism that likely involves the down-regulation of BST-2 from the cell surface. Here, we show that the optimal removal of BST-2 from the plasma membrane by Vpu requires the cellular protein β-TrCP, a substrate adaptor for a multi-subunit SCF E3 ubiquitin ligase complex and a known Vpu-interacting protein. β-TrCP is also required for the optimal enhancement of virion-release by Vpu. Mutations in the DSGxxS β-TrCP binding-motif of Vpu impair both the down-regulation of BST-2 and the enhancement of virion-release. Such mutations also confer dominant-negative activity, consistent with a model in which Vpu links BST-2 to β-TrCP. Optimal down-regulation of BST-2 from the cell surface by Vpu also requires the endocytic clathrin adaptor AP-2, although the rate of endocytosis is not increased; these data suggest that Vpu induces post-endocytic membrane trafficking events whose net effect is the removal of BST-2 from the cell surface. In addition to its marked effect on cell-surface levels, Vpu modestly decreases the total cellular levels of BST-2. The decreases in cell-surface and intracellular BST-2 are inhibited by bafilomycin A1, an inhibitor of endosomal acidification; these data suggest that Vpu induces late endosomal targeting and partial degradation of BST-2 in lysosomes. The Vpu-mediated decrease in surface expression is associated with reduced co-localization of BST-2 and the virion protein Gag along the plasma membrane. Together, the data support a model in which Vpu co-opts the β-TrCP/SCF E3 ubiquitin ligase complex to induce endosomal trafficking events that remove BST-2 from its site of action as a virion-tethering factor

Thermodynamic calculations of oxygen self-diffusion in mixed-oxide nuclear fuels

Molecular dynamics calculations are used to provide a self-consistent prediction of the elastic, thermal expansion and oxygen self-diffusion properties of mixed oxide nuclear fuels at arbitrary compositions.</p

The mediating effect of task presentation on collaboration and children's acquisition of scientific reasoning

There has been considerable research concerning peer interaction and the acquisition of children's scientific reasoning. This study investigated differences in collaborative activity between pairs of children working around a computer with pairs of children working with physical apparatus and related any differences to the development of children's scientific reasoning. Children aged between 9 and 10 years old (48 boys and 48 girls) were placed into either same ability or mixed ability pairs according to their individual, pre-test performance on a scientific reasoning task. These pairs then worked on either a computer version or a physical version of Inhelder and Piaget's (1958) chemical combination task. Type of presentation was found to mediate the nature and type of collaborative activity. The mixed-ability pairs working around the computer talked proportionally more about the task and management of the task; had proportionally more transactive discussions and used the record more productively than children working with the physical apparatus. Type of presentation was also found to mediated children's learning. Children in same ability pairs who worked with the physical apparatus improved significantly more than same ability pairs who worked around the computer. These findings were partially predicted from a socio-cultural theory and show the importance of tools for mediating collaborative activity and collaborative learning

Dealing with mobility: Understanding access anytime, anywhere

The rapid and accelerating move towards the adoption and use of mobile technologies has increasingly provided people and organisations with the ability to work away from the office and on the move. The new ways of working afforded by these technologies are often characterised in terms of access to information and people ‘anytime, anywhere’. This paper presents a study of mobile workers that highlights different facets of access to remote people and information, and different facets of anytime, anywhere. Four key factors in mobile work are identified from the study: the role of planning, working in ‘dead time’, accessing remote technological and informational resources, and monitoring the activities of remote colleagues. By reflecting on these issues, we can better understand the role of technology and artefact use in mobile work and identify the opportunities for the development of appropriate technological solutions to support mobile workers

Lattice setup for quantum field theory in AdS2

Holographic conformal field theories (CFTs) are usually studied in a limit where the gravity description is weakly coupled. By contrast, lattice quantum field theory can be used as a tool for doing computations in a wider class of holographic CFTs where nongravitational interactions in AdS become strong, and gravity is decoupled. We take preliminary steps for studying such theories on the lattice by constructing the discretized theory of a scalar field in AdS 2 and investigating its approach to the continuum limit in the free and perturbative regimes. Our main focus is on finite sublattices of maximally symmetric tilings of hyperbolic space. Up to boundary effects, these tilings preserve the triangle group as a large discrete subgroup of AdS 2 , but have a minimum lattice spacing that is comparable to the radius of curvature of the underlying spacetime. We quantify the effects of the lattice spacing as well as the boundary effects, and find that they can be accurately modeled by modifications within the framework of the continuum limit description. We also show how to do refinements of the lattice that shrink the lattice spacing at the cost of breaking the triangle group symmetry of the maximally symmetric tilings.Published versio

Near-IR search for lensed supernovae behind galaxy clusters: I. Observations and transient detection efficiency

Massive galaxy clusters at intermediate redshift can magnify the flux of distant background sources by several magnitudes and we exploit this effect to search for lensed distant supernovae that may otherwise be too faint to be detected. A supernova search was conducted at near infrared wavelengths using the ISAAC instrument at the VLT. The galaxy clusters Abell 1689, Abell 1835 and AC114 were observed at multiple epochs of 2 hours of exposure time, separated by a month. Image-subtraction techniques were used to search for transient objects with light curve properties consistent with supernovae, both in our new and archival ISAAC/VLT data. The limiting magnitude of the individual epochs was estimated by adding artificial stars to the subtracted images. Most of the epochs reach 90% detection efficiency at SZ(J) ~= 23.8-24.0 mag (Vega). Two transient objects, both in archival images of Abell 1689 and AC114, were detected. The transient in AC114 coincides - within the position uncertainty - with an X-ray source and is likely to be a variable AGN at the cluster redshift. The transient in Abell 1689 was found at SZ=23.24 mag, ~0.5 arcsec away from a galaxy with photometric redshift z=0.6 +/-0.15. The light curves and the colors of the transient are consistent with a reddened Type IIP supernova at redshift z=0.59 +/- 0.05. The lensing model of Abell 1689 predicts ~1.4 mag of magnification at the position of the transient, making it the most magnified supernova ever found and only the second supernova found behind a galaxy cluster. Our pilot survey has demonstrated the feasibility to find distant gravitationally magnified supernovae behind massive galaxy clusters. One likely supernova was found behind Abell 1689, in accordance with the expectations for this survey, as shown in an accompanying analysis paper.Comment: Language-edited version, 9 pages, 6 figures, accepted by A&

UV Absorption Lines from High-Velocity Gas in the Vela Supernova Remnant: New insights from STIS Echelle Observations of HD72089

The star HD72089 is located behind the Vela supernova remnant and shows a complex array of high and low velocity interstellar absorption features arising from shocked clouds. A spectrum of this star was recorded over the wavelength range 1196.4 to 1397.2 Angstroms at a resolving power lambda/Delta lambda = 110,000 and signal-to-noise ratio of 32 by STIS on the Hubble Space Telescope. We have identified 7 narrow components of C I and have measured their relative populations in excited fine-structure levels. Broader features at heliocentric velocities ranging from -70 to +130 km/s are seen in C II, N I, O I, Si II, S II and Ni II. In the high-velocity components, the unusually low abundances of N I and O I, relative to S II and Si II, suggest that these elements may be preferentially ionized to higher stages by radiation from hot gas immediately behind the shock fronts.Comment: 11 pages, 2 figures, Latex. Submitted for the special HST ERO issue of the Astrophysical Journal Letter

Near-IR Search for Lensed Supernovae Behind Galaxy Clusters - II. First Detection and Future Prospects

Powerful gravitational telescopes in the form of massive galaxy clusters can be used to enhance the light collecting power over a limited field of view by about an order of magnitude in flux. This effect is exploited here to increase the depth of a survey for lensed supernovae at near-IR wavelengths. A pilot SN search program conducted with the ISAAC camera at VLT is presented. Lensed galaxies behind the massive clusters A1689, A1835 and AC114 were observed for a total of 20 hours split into 2, 3 and 4 epochs respectively, separated by approximately one month to a limiting magnitude J<24 (Vega). Image subtractions including another 20 hours worth of archival ISAAC/VLT data were used to search for transients with lightcurve properties consistent with redshifted supernovae, both in the new and reference data. The feasibility of finding lensed supernovae in our survey was investigated using synthetic lightcurves of supernovae and several models of the volumetric Type Ia and core-collapse supernova rates as a function of redshift. We also estimate the number of supernova discoveries expected from the inferred star formation rate in the observed galaxies. The methods consistently predict a Poisson mean value for the expected number of SNe in the survey between N_SN=0.8 and 1.6 for all supernova types, evenly distributed between core collapse and Type Ia SN. One transient object was found behind A1689, 0.5" from a galaxy with photometric redshift z_gal=0.6 +- 0.15. The lightcurve and colors of the transient are consistent with being a reddened Type IIP SN at z_SN=0.59. The lensing model predicts 1.4 magnitudes of magnification at the location of the transient, without which this object would not have been detected in the near-IR ground based search described in this paper (unlensed magnitude J~25). (abridged)Comment: Accepted by AA, matches journal versio

The human semicircular canal model of galvanic vestibular stimulation

A vector summation model of the action of galvanic stimuli on the semicircular canals has been shown to explain empirical balance and perceptual responses to binaural-bipolar stimuli. However, published data suggest binaural-monopolar stimuli evoke responses that are in the reverse direction of the model prediction. Here, we confirm this by measuring balance responses to binaural-monopolar stimulation as movements of the upper trunk. One explanation for the discrepancy is that the galvanic stimulus might evoke an oppositely directed balance response from the otolith organs that sums with and overrides the semicircular canal response. We tested this hypothesis by measuring sway responses across the full range of head pitch. The results showed some modulation of sway with pitch such that the maximal response occurred with the head in the primary position. However, the effect fell a long way short of that required to reverse the canal sway response. This indicates that the model is incomplete. Here, we examine alterations to the model that could explain both the bipolar and monopolar-evoked behavioural responses. An explanation was sought by remodelling the canal response with more recent data on the orientation of the individual canals. This improved matters but did not reverse the model prediction. However, the model response could be reversed by either rotating the entire labyrinth in the skull or by altering the gains of the individual canals. The most parsimonious solution was to use the more recent canal orientation data coupled with a small increase in posterior canal gain