Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence

Viral immune evasion strategies target key aspects of the host antiviral response. Recently, it has been recognized that Toll-like receptors (TLRs) have a role in innate defense against viruses. Here, we define the function of the vaccinia virus (VV) protein A46R and show it inhibits intracellular signalling by a range of TLRs. TLR signalling is triggered by homotypic interactions between the Toll-like-interleukin-1 resistance (TIR) domains of the receptors and adaptor molecules. A46R contains a TIR domain and is the only viral TIR domain-containing protein identified to date. We demonstrate that A46R targets the host TIR adaptors myeloid differentiation factor 88 (MyD88), MyD88 adaptor-like, TIR domain-containing adaptor inducing IFN-beta (TRIF), and the TRIF-related adaptor molecule and thereby interferes with downstream activation of mitogen-activated protein kinases and nuclear factor kappaB. TRIF mediates activation of interferon (IFN) regulatory factor 3 (IRF3) and induction of IFN-beta by TLR3 and TLR4 and suppresses VV replication in macrophages. Here, A46R disrupted TRIF-induced IRF3 activation and induction of the TRIF-dependent gene regulated on activation, normal T cell expressed and secreted. Furthermore, we show that A46R is functionally distinct from another described VV TLR inhibitor, A52R. Importantly, VV lacking the A46R gene was attenuated in a murine intranasal model, demonstrating the importance of A46R for VV virulence

Bound-State Representation of Scattering Solutions

Journals published by the American Physical Society can be found at http://publish.aps.org

Totally Microscopic Description of N-O-16 Elastic-Scattering

Journals published by the American Physical Society can be found at http://publish.aps.org

Anomalous magnetic phase in an undistorted pyrochlore oxide Cd2Os2O7 induced by geometrical frustration

We report on the muon spin rotation/relaxation study of a pyrochlore oxide, Cd2Os2O7, which exhibits a metal-insulator (MI) transition at T_{MI}~225 K without structural phase transition. It reveals strong spin fluctuation (>10^8/s) below the MI transition, suggesting a predominant role of geometrical spin frustration amongst Os^{5+} ions. Meanwhile, upon further cooling, a static spin density wave discontinuously develops below T_{SDW}~150 K. These observations strongly suggest the occurrence of an anomalous magnetic transition and associated change in the local spin dynamics in undistorted pyrochlore antiferromagnet.Comment: 5 pages, 4 figure

Going beyond defining: Preschool educators\u27 use of knowledge in their pedagogical reasoning about vocabulary instruction

Previous research investigating both the knowledge of early childhood educators and the support for vocabulary development present in early childhood settings has indicated that both educator knowledge and enacted practice are less than optimal, which has grave implications for children\u27s early vocabulary learning and later reading achievement. Further, the nature of the relationship between educators\u27 knowledge and practice is unclear, making it difficult to discern the best path towards improved knowledge, practice, and children\u27s vocabulary outcomes. The purpose of the present study was to add to the existing literature by using stimulated recall interviews and a grounded approach to examine how 10 preschool educators used their knowledge to made decisions about their moment-to-moment instruction in support of children\u27s vocabulary development. Results indicate that educators were thinking in highly context-specific ways about their goals and strategies for supporting vocabulary learning, taking into account important knowledge of their instructional history with children and of the children themselves to inform their decision making in the moment. In addition, they reported thinking about research-based goals and strategies for supporting vocabulary learning that went beyond simply defining words for children. Implications for research and professional development are discussed

Exploring young people's and youth workers' experiences of spaces for ‘youth development’: creating cultures of participation

The paper focuses on the emergence of ‘positive youth development’ and its impact on older, more established practices of working with young people, such as youth work. Drawing on ethnographic fieldwork in England between 2004 and 2006, in particular young people's and youth workers' accounts of participating in youth work, the analysis engages with the social spaces in which youth work takes place and asks key questions about why young people might participate in youth spaces, what they get out of participating and how such spaces can promote cultures of participation. The analysis shows that such spaces provide young people and their communities with biographical continuity and time becomes a key component for sustaining such spaces. The argument is made for a more nuanced understanding of what young people get out of their participation in youth spaces, and for an epistemological approach to youth praxis that embraces the messiness and inequalities of lived experience

Associahedra via spines

An associahedron is a polytope whose vertices correspond to triangulations of a convex polygon and whose edges correspond to flips between them. Using labeled polygons, C. Hohlweg and C. Lange constructed various realizations of the associahedron with relevant properties related to the symmetric group and the classical permutahedron. We introduce the spine of a triangulation as its dual tree together with a labeling and an orientation. This notion extends the classical understanding of the associahedron via binary trees, introduces a new perspective on C. Hohlweg and C. Lange's construction closer to J.-L. Loday's original approach, and sheds light upon the combinatorial and geometric properties of the resulting realizations of the associahedron. It also leads to noteworthy proofs which shorten and simplify previous approaches.Comment: 27 pages, 11 figures. Version 5: minor correction

Seismicity and Pn Velocity Structure of Central West Antarctica

We have located 117 previously undetected seismic events mainly occurring between 2015 and 2017 that originated from glacial, tectonic, and volcanic processes in central West Antarctica using data recorded on Polar Earth Observing Network (POLENET/ANET) and UK Antarctic Network (UKANET) seismic stations. The seismic events, with local magnitudes (ML) ranging from 1.1 to 3.5, are predominantly clustered in four geographic regions; the Ellsworth Mountains, Thwaites Glacier, Pine Island Glacier, and Mount Takahe. Eighteen of the events are in the Ellsworth Mountains and can be attributed to a mixture of glacial and tectonic processes. The largest event noted in this study was a mid‐crustal (∼19 km focal depth; ML 3.5) normal mechanism earthquake beneath Thwaites Glacier. We also located 91 glacial events near the grounding zones of Thwaites Glacier and Pine Island Glacier that are predominantly associated with time periods of significant calving activity. Eight events, likely arising from volcano‐tectonic processes, occurred beneath Mount Takahe. Using Pn travel times from the seismic events, we find laterally variable uppermost mantle structure in central West Antarctica. On average, the Ellsworth Mountains are underlain by a faster mantle lid (VPn = ∼8.4 km/s) compared to the Amundsen Sea Embayment region (VPn = ∼8.1 km/s). Within the Amundsen Sea Embayment itself, we find mantle lid velocities ranging from ∼8.05 to 8.18 km/s. Laterally heterogeneous uppermost mantle structure, indicative of variable thermal and rheological structure, likely influences both geothermal heat flux and glacial isostatic adjustment spatial patterns and rates within central West Antarctica

Syn‐rift sediment gravity flow deposition on a Late Jurassic fault‐terraced slope, northern North Sea

Structurally controlled bathymetry in rifts has a significant influence on sediment routing pathways and depositional architecture of sediment gravity flow deposits. In contrast to rift segments characterized by crustal-scale half-grabens, the tectono-stratigraphic evolution of deep-water rift domains characterised by distributed faulting on narrow fault terraces has received little attention. We use 3D broadband seismic data, calibrated by boreholes, from the Lomre and Uer terraces in the northern North Sea rift to investigate Late Jurassic syn-rift sediment gravity flow systems on fault-terraced slopes. The sediment gravity flow fairways were sourced from hinterland drainages via basin margin deltaic systems on the Horda Platform to the southeast. The deep-water sedimentary systems evolve from initial, widespread submarine channelized lobe complexes, through submarine channels, to incised submarine canyons. This progressive confinement of the sediment gravity flow system was concomitant with progressive localization of strain onto the main terrace-bounding faults. Although the normal fault network on the terraces has local impact on deep-water sediment transport and the architecture of gravity flow deposits, it is the regional basin margin to rift axis gradient that dominantly controls deep-water sediment routing. Furthermore, the gravity flow deposits on the Lomre and Uer terraces were predominantly sourced by rift margin deltaic systems, not from erosion of local uplifted footwall crests, emphasising the significance of hinterland catchments in the development of volumetrically significant deep-water syn-rift depositional systems

Success for All in England: Results From the Third Year of a National Evaluation

This article reports the third-year findings of a longitudinal evaluation in England of Success for All (SFA), a comprehensive literacy program. Eighteen SFA schools across England and 18 control schools, matched on prior achievement and demographics, were included in this quasi-experimental study. The results of hierarchical linear modeling analysis reveal a statistically significant positive school-level effect for SFA schools compared with control schools on standardized reading measures of word-level and decoding skills, and there were directionally positive but nonsignificant school-level effects on measures of comprehension and fluency. Practical and policy implications of these findings are discussed, particularly as they relate to recent English government policies encouraging schools to implement research-proven approaches