Vaccinia protein C16 blocks innate immune sensing of DNA by binding the Ku complex

VACV gene C16L encodes a 37-kDa protein that is highly conserved in orthopoxviruses and functions as an immunomodulator. Intranasal infection of mice with a virus lacking C16L (vΔC16) induced less weight loss, fewer signs of illness and increased infiltration of leukocytes to the lungs compared with wild-type virus. To understand C16’s mechanism of action, tandem affinity purification and mass spectrometry were used to identify C16 binding partners. This revealed that Ku70, Ku80 and PHD2 interact with C16 in cells. Ku70 and Ku80 constitute the Ku heterodimer, a well characterised DNA repair complex. MEFs lacking Ku, or the other component of the DNA-dependent protein kinase (DNA-PK) complex, the catalytic subunit of DNA-PK (DNA-PKcs), were shown to be deficient in the upregulation of IRF-3-dependent genes such as Cxcl10, Il6 and Ifnb in response to transfection of DNA, but not poly (I:C). Furthermore, following infection of MEFs with VACV strain MVA the activation of Cxcl10 or Il6 transcription was dependent on DNA-PK. Therefore, DNA-PK is a DNA sensor capable of detecting poxvirus DNA and activating IRF-3-dependent innate immunity. C16 inhibited the binding of Ku to DNA, and therefore inhibited DNA-mediated induction of Cxcl10 and Il-6 in MEFs. The role of C16 in vivo was also examined: infection with vΔC16 led to increased production of Cxcl10 and Il-6 following intranasal infection of mice compared with wild-type virus. C16 is therefore an inhibitor of DNA-PK-mediated DNA sensing and innate immune activation. C16 was also shown to bind to PHD2, an enzyme involved in regulation of hypoxic signalling. VACV was found to activate the transcription of hypoxia-related genes, and C16 expression in cells was also capable of doing this. The role of hypoxic signalling in VACV infection remains poorly understood

'Learning Styles' and 'Approaches to Studying' in Sports-Related Programmes: Relationships to Academic Achievement and Implications for Successful Learning, Teaching and Assessment: Project Report Summary

There are relatively few recent investigations that have addressed the issues of preferred learning styles and approaches to studying in sports-related disciplines such as: Sports Studies; Sports and Exercise Science; Coaching Science; Sport and Leisure Management and Outdoor Recreation Management. The purpose of this study was therefore to examine student learning across a range of sport-related programmes at a UK University College. It applied tools from two related, but different, educational research paradigms: approaches to learning and learning styles analysis. Thus, these differing means of researching student learning were tested against the same student group. Results were compared to students’ perceptions of their own developing autonomy of learning and achieved grades; insights were generated into the particular learning approaches and styles of sports students; and tentative recommendations are made on the implications of the findings for higher education teachers seeking to promote improvements in the learning of sports subjects

On rigidity of locally symmetric spaces

In this note I generalize the classical results of Calabi-Vesentini to certain non-compact locally symmetric domains, namely those that are quotients of a hermitian symmetric domain by a neat arithmetic subgroup of the group of its holomorphic automorphisms.Comment: To be published in the M\"unster Journal of Mathematic

Beyond the Standard Model searches with top quarks at D0

Due to its high mass and short lifetime, the top quark plays an important role in checking the Standard Model of particle physics. In this report, we pr\ esent a variety of searches for physics beyond the Standard Model, involving top quarks, at the D0 detector at the Fermilab Tevatron collider. Specifically, we present searches in top quark pair production, single top quark production and top quark decays. The search spectra discussed here involve a search for $t\bar{t}$ resonances, associated production of Higgs bosons and $t\bar{t}$, charged Higgs bosons and heavy gauge $W^{'}$ bosons. Furthermore, we measure the forward-backward charge asymmetry and a ratio of branching fractions.Comment: To appear in the proceedings of 2009 Europhysics Conference on High Energy Physics: HEP 2009 (EPS-HEP 2009), Cracow, Poland, 16-22 Jul 2009. 5 pages, 2 figures

Searches for New Physics in the Top Sector at the Tevatron

The top quark, discovered in 1995 by the CDF and D0 collaborations at the Tevatron collider at Fermilab, is the heaviest known elementary particle today. Due to its high mass and short lifetime, the top quark plays a special role in searching for physics beyond the Standard Model. In this article, recent results of searches for new physics in the top sector, performed by CDF and D0, are presented. In particular, we discuss the search for ttbar resonances, for tj resonances, the search for heavy fourth generation quarks, for dark matter produced in association with single tops, the study of anomalous couplings, the search for boosted top quarks as well as the analysis of Lorentz Invariance violation in the top quark sector.Comment: 4 pages, proceedings for the DIS2012 conference, Bonn, German

Recognising Multidimensional Euclidean Preferences

Euclidean preferences are a widely studied preference model, in which decision makers and alternatives are embedded in d-dimensional Euclidean space. Decision makers prefer those alternatives closer to them. This model, also known as multidimensional unfolding, has applications in economics, psychometrics, marketing, and many other fields. We study the problem of deciding whether a given preference profile is d-Euclidean. For the one-dimensional case, polynomial-time algorithms are known. We show that, in contrast, for every other fixed dimension d > 1, the recognition problem is equivalent to the existential theory of the reals (ETR), and so in particular NP-hard. We further show that some Euclidean preference profiles require exponentially many bits in order to specify any Euclidean embedding, and prove that the domain of d-Euclidean preferences does not admit a finite forbidden minor characterisation for any d > 1. We also study dichotomous preferencesand the behaviour of other metrics, and survey a variety of related work.Comment: 17 page