Minimal cubic cones via Clifford algebras

We construct two infinite families of algebraic minimal cones in $R^{n}$. The first family consists of minimal cubics given explicitly in terms of the Clifford systems. We show that the classes of congruent minimal cubics are in one to one correspondence with those of geometrically equivalent Clifford systems. As a byproduct, we prove that for any $n\ge4$, $n\ne 16k+1$, there is at least one minimal cone in $R^{n}$ given by an irreducible homogeneous cubic polynomial. The second family consists of minimal cones in $R^{m^2}$, $m\ge2$, defined by an irreducible homogeneous polynomial of degree $m$. These examples provide particular answers to the questions on algebraic minimal cones posed by Wu-Yi Hsiang in the 1960's.Comment: Final version, corrects typos in Table

‘Oh you don’t want asylum seekers, oh you’re just racist’: A discursive analysis of discussions about whether it’s racist to oppose asylum seeking

ABSTRACT In this article, we explore how speakers discuss whether or not it is racist to oppose asylum seekers. A discourse analysis is conducted on the parts of a corpus of data collected from focus groups with undergraduate students talking about asylum seeking in which they were asked if it is racist to oppose asylum. It is shown that speakers use the word ‘just’ as part of a contrast structure which is used to present a topic as self-evidently unreasonable. While some participants orient to the taboo against prejudice, it is shown that there is also an orientation to the idea that accusations of racism are unreasonable and that opposition to asylum is usually based on practical and economic reasons rather than racism. These findings are discussed in light of the growing literature surrounding the changing nature of race talk and new taboos on accusations of racism

Bounds on the heat kernel of the Schroedinger operator in a random electromagnetic field

We obtain lower and upper bounds on the heat kernel and Green functions of the Schroedinger operator in a random Gaussian magnetic field and a fixed scalar potential. We apply stochastic Feynman-Kac representation, diamagnetic upper bounds and the Jensen inequality for the lower bound. We show that if the covariance of the electromagnetic (vector) potential is increasing at large distances then the lower bound is decreasing exponentially fast for large distances and a large time.Comment: some technical improvements, new references, to appear in Journ.Phys.

Structural basis for pure antagonism of integrin αVβ3 by a high affinity form of fibronectin

Integrins are important therapeutic targets. However, current RGD-based anti-integrin drugs are also partial agonists, inducing conformational changes that trigger potentially fatal immune reactions and paradoxical cell adhesion. Here we describe the first crystal structure of αVβ3 bound to a physiologic ligand: the 10th type III RGD-domain of wild-type fibronectin (wtFN10), or to a high affinity mutant (hFN10) that acts as a pure antagonist. Comparison of these structures revealed a central π - π interaction between Trp1496 in the RGD-containing loop of hFN10 and Tyr122 of the β3-subunit that blocked conformational changes triggered by wtFN10, and trapped hFN10-bound αVβ3 in an inactive conformation. Removing the Trp1496 or Tyr122 side-chains, or reorienting Trp1496 away from Tyr122, converted hFN10 into a partial agonist. The findings offer new insights on the mechanism of integrin activation and a basis for design of RGD-based pure antagonists

Integrin control of the transforming growth factor-β pathway in glioblastoma

Transforming growth factor-β is a central mediator of the malignant phenotype of glioblastoma, the most common and malignant form of intrinsic brain tumours. Transforming growth factor-β promotes invasiveness and angiogenesis, maintains cancer cell stemness and induces profound immunosuppression in the host. Integrins regulate cellular adhesion and transmit signals important for cell survival, proliferation, differentiation and motility, and may be involved in the activation of transforming growth factor-β. We report that αvβ3, αvβ5 and αvβ8 integrins are broadly expressed not only in glioblastoma blood vessels but also in tumour cells. Exposure to αv, β3 or β5 neutralizing antibodies, RNA interference-mediated integrin gene silencing or pharmacological integrin inhibition using the cyclic RGD peptide EMD 121974 (cilengitide) results in reduced phosphorylation of Smad2 in most glioma cell lines, including glioma-initiating cell lines and reduced transforming growth factor-β-mediated reporter gene activity, coinciding with reduced transforming growth factor-β protein levels in the supernatant. Time course experiments indicated that the loss of transforming growth factor-β bioactivity due to integrin inhibition likely results from two distinct mechanisms: an early effect on activation of preformed inactive protein, and second, major effect on transforming growth factor-β gene transcription as confirmed by decreased activity of the transforming growth factor-β gene promoter and decreased transforming growth factor-β1 and transforming growth factor-β2 messenger RNA expression levels. In vivo, EMD 121974 (cilengitide), which is currently in late clinical development as an antiangiogenic agent in newly diagnosed glioblastoma, was a weak antagonist of pSmad2 phosphorylation. These results validate integrin inhibition as a promising strategy not only to inhibit angiogenesis, but also to block transforming growth factor-β-controlled features of malignancy including invasiveness, stemness and immunosuppression in human glioblastom

SICANE: a Detector Array for the Measurement of Nuclear Recoil Quenching Factors using Monoenergetic Neutron Beam

SICANE is a neutron scattering multidetector facility for the determination of the quenching factor (ratio of the response to nuclear recoils and to electrons) of cryogenic detectors used in direct WIMP searches. Well collimated monoenergetic neutron beams are obtained with inverse (p,n) reactions. The facility is described, and results obtained for the quenching factors of scintillation in NaI(Tl) and of heat and ionization in Ge are presented.Comment: 30 pages, Latex, 11 figures. Submitted to NIM

High rates of infection by blood parasites during the nestling phase in UK Columbids with notes on ecological associations

Studies of blood parasite infection in nestling birds rarely find a high prevalence of infection. This is likely due to a combination of short nestling periods (limiting the age at which nestlings can be sampled) and long parasite prepatent periods before gametocytes can be detected in peripheral blood. Here we examine rates of blood parasite infection in nestlings from three Columbid species in the UK. We use this system to address two key hypotheses in the epidemiology of avian haemoparasites: first, that nestlings in open nests have a higher prevalence of infection; and second, that nestlings sampled at 14 days old have a higher apparent infection rate than those sampled at 7 days old. Open-nesting individuals had a 54% infection rate compared with 25% for box-nesters, probably due to an increased exposure of open-nesting species to dipteran vectors. Nestlings sampled at 14 days had a 68% infection rate compared with 32% in nestlings sampled at 7 days, suggesting that rates of infection in the nest are high. Further work should examine nestlings post-fledging to identify rates of successful parasite infection (as opposed to abortive development within a dead-end host) as well as impacts on host post-fledging survival and behaviour

Maternal psychological distress in primary care and association with child behavioural outcomes at age three

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers’ mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00787-015-0777-2) contains supplementary material, which is available to authorized users

Background discrimination capabilities of a heat and ionization germanium cryogenic detector

The discrimination capabilities of a 70 g heat and ionization Ge bolometer are studied. This first prototype has been used by the EDELWEISS Dark Matter experiment, installed in the Laboratoire Souterrain de Modane, for direct detection of WIMPs. Gamma and neutron calibrations demonstrate that this type of detector is able to reject more than 99.6% of the background while retaining 95% of the signal, provided that the background events distribution is not biased towards the surface of the Ge crystal. However, the 1.17 kg.day of data taken in a relatively important radioactive environment show an extra population slightly overlapping the signal. This background is likely due to interactions of low energy photons or electrons near the surface of the crystal, and is somewhat reduced by applying a higher charge-collecting inverse bias voltage (-6 V instead of -2 V) to the Ge diode. Despite this contamination, more than 98% of the background can be rejected while retaining 50% of the signal. This yields a conservative upper limit of 0.7 event.day^{-1}.kg^{-1}.keV^{-1}_{recoil} at 90% confidence level in the 15-45 keV recoil energy interval; the present sensitivity appears to be limited by the fast ambient neutrons. Upgrades in progress on the installation are summarized.Comment: Submitted to Astroparticle Physics, 14 page

Crystal structure of the complete integrin αVβ3 ectodomain plus an α/β transmembrane fragment

We determined the crystal structure of 1TM-αVβ3, which represents the complete unconstrained ectodomain plus short C-terminal transmembrane stretches of the αV and β3 subunits. 1TM-αVβ3 is more compact and less active in solution when compared with ΔTM-αVβ3, which lacks the short C-terminal stretches. The structure reveals a bent conformation and defines the α–β interface between IE2 (EGF-like 2) and the thigh domains. Modifying this interface by site-directed mutagenesis leads to robust integrin activation. Fluorescent lifetime imaging microscopy of inactive full-length αVβ3 on live cells yields a donor–membrane acceptor distance, which is consistent with the bent conformation and does not change in the activated integrin. These data are the first direct demonstration of conformational coupling of the integrin leg and head domains, identify the IE2–thigh interface as a critical steric barrier in integrin activation, and suggest that inside-out activation in intact cells may involve conformational changes other than the postulated switch to a genu-linear state