Normal human breast xenografts activate N-nitrosodimethylamine: identification of potential target cells for an environmental nitrosamine.

Normal human breast tissue maintained as xenografts in female Balb/c (nu/nu) athymic mice is capable of metabolising N-nitrosodimethylamine (NDMA) to active intermediates that will react with DNA. Administration of NDMA to mice with slow-release implants of 17 beta-oestradiol which provide human physiological (luteal phase) circulating oestrogen levels and increase cell proliferation in the xenograft (Laidlaw et al., 1992), leads to an apparent increase in the extent of reaction with DNA compared to controls without oestrogen implants. In mice with oestrogen implants, measurements of the amounts of the promutagenic lesion, O6-methyl-2'-deoxyguanosine formed in DNA clearly indicated a dose related increase in the extent of reaction. Detection of O6-methyl-2'-deoxyguanosine using immunohistochemical procedures revealed that the nuclei of cells of the glandular epithelium, supportive tissue and adipose tissue, in decreasing order of prevalence, were positively stained for the presence of this DNA lesion. Epithelial cells, which are the putative target cells for carcinogenesis in the breast, are therefore prone to promutagenic damage as a result of exposure to an environmental nitrosamine

Analytic Representation of Finite Quantum Systems

A transform between functions in R and functions in Zd is used to define the analogue of number and coherent states in the context of finite d-dimensional quantum systems. The coherent states are used to define an analytic representation in terms of theta functions. All states are represented by entire functions with growth of order 2, which have exactly d zeros in each cell. The analytic function of a state is constructed from its zeros. Results about the completeness of finite sets of coherent states within a cell are derived

No-Boundary Theta-Sectors in Spatially Flat Quantum Cosmology

Gravitational theta-sectors are investigated in spatially locally homogeneous cosmological models with flat closed spatial surfaces in 2+1 and 3+1 spacetime dimensions. The metric ansatz is kept in its most general form compatible with Hamiltonian minisuperspace dynamics. Nontrivial theta-sectors admitting a semiclassical no-boundary wave function are shown to exist only in 3+1 dimensions, and there only for two spatial topologies. In both cases the spatial surface is nonorientable and the nontrivial no-boundary theta-sector unique. In 2+1 dimensions the nonexistence of nontrivial no-boundary theta-sectors is shown to be of topological origin and thus to transcend both the semiclassical approximation and the minisuperspace ansatz. Relation to the necessary condition given by Hartle and Witt for the existence of no-boundary theta-states is discussed.Comment: 30 p

Running couplings and triviality of field theories on non-commutative spaces

We examine the issue of renormalizability of asymptotically free field theories on non-commutative spaces. As an example, we solve the non-commutative O(N) invariant Gross-Neveu model at large N. On commutative space this is a renormalizable model with non-trivial interactions. On the noncommutative space, if we take the translation invariant ground state, we find that the model is non-renormalizable. Removing the ultraviolet cutoff yields a trivial non-interacting theory.Comment: Latex, 9p, Minor changes, references and clarifications are adde

Testing spatial noncommutativiy via the Aharonov-Bohm effect

The possibility of detecting noncommutative space relics is analyzed using the Aharonov-Bohm effect. We show that, if space is noncommutative, the holonomy receives non-trivial kinematical corrections that will produce a diffraction pattern even when the magnetic flux is quantized. The scattering problem is also formulated, and the differential cross section is calculated. Our results can be extrapolated to high energy physics and the bound $\theta \sim [ 10 {TeV}]^{-2}$ is found. If this bound holds, then noncommutative effects could be explored in scattering experiments measuring differential cross sections for small angles. The bound state Aharonov- Bohm effect is also discussed.Comment: 16 pp, Revtex 4, 2 fig, new references added. To appear in PR

Two-Loop Analysis of Non-abelian Chern-Simons Theory

Perturbative renormalization of a non-Abelian Chern-Simons gauge theory is examined. It is demonstrated by explicit calculation that, in the pure Chern-Simons theory, the beta-function for the coefficient of the Chern-Simons term vanishes to three loop order. Both dimensional regularization and regularization by introducing a conventional Yang-Mills component in the action are used. It is shown that dimensional regularization is not gauge invariant at two loops. A variant of this procedure, similar to regularization by dimensional reduction used in supersymmetric field theories is shown to obey the Slavnov-Taylor identity to two loops and gives no renormalization of the Chern-Simons term. Regularization with Yang-Mills term yields a finite integer-valued renormalization of the coefficient of the Chern-Simons term at one loop, and we conjecture no renormalization at higher order. We also examine the renormalization of Chern-Simons theory coupled to matter. We show that in the non-abelian case the Chern-Simons gauge field as well as the matter fields require infinite renormalization at two loops and therefore obtain nontrivial anomalous dimensions. We show that the beta function for the gauge coupling constant is zero to two-loop order, consistent with the topological quantization condition for this constant.Comment: 48 pages, UU/HEP/91/12; file format changed to standard Latex to solve the problem with printin

Threat-sensitive anti-predator defence in precocial wader, the northern lapwing Vanellus vanellus

Birds exhibit various forms of anti-predator behaviours to avoid reproductive failure, with mobbing—observation, approach and usually harassment of a predator—being one of the most commonly observed. Here, we investigate patterns of temporal variation in the mobbing response exhibited by a precocial species, the northern lapwing (Vanellus vanellus). We test whether brood age and self-reliance, or the perceived risk posed by various predators, affect mobbing response of lapwings. We quantified aggressive interactions between lapwings and their natural avian predators and used generalized additive models to test how timing and predator species identity are related to the mobbing response of lapwings. Lapwings diversified mobbing response within the breeding season and depending on predator species. Raven Corvus corax, hooded crow Corvus cornix and harriers evoked the strongest response, while common buzzard Buteo buteo, white stork Ciconia ciconia, black-headed gull Chroicocephalus ridibundus and rook Corvus frugilegus were less frequently attacked. Lapwings increased their mobbing response against raven, common buzzard, white stork and rook throughout the breeding season, while defence against hooded crow, harriers and black-headed gull did not exhibit clear temporal patterns. Mobbing behaviour of lapwings apparently constitutes a flexible anti-predator strategy. The anti-predator response depends on predator species, which may suggest that lapwings distinguish between predator types and match mobbing response to the perceived hazard at different stages of the breeding cycle. We conclude that a single species may exhibit various patterns of temporal variation in anti-predator defence, which may correspond with various hypotheses derived from parental investment theory

HARP/ACSIS: A submillimetre spectral imaging system on the James Clerk Maxwell Telescope

This paper describes a new Heterodyne Array Receiver Programme (HARP) and Auto-Correlation Spectral Imaging System (ACSIS) that have recently been installed and commissioned on the James Clerk Maxwell Telescope (JCMT). The 16-element focal-plane array receiver, operating in the submillimetre from 325 to 375 GHz, offers high (three-dimensional) mapping speeds, along with significant improvements over single-detector counterparts in calibration and image quality. Receiver temperatures are $\sim$120 K across the whole band and system temperatures of $\sim$300K are reached routinely under good weather conditions. The system includes a single-sideband filter so these are SSB figures. Used in conjunction with ACSIS, the system can produce large-scale maps rapidly, in one or more frequency settings, at high spatial and spectral resolution. Fully-sampled maps of size 1 square degree can be observed in under 1 hour. The scientific need for array receivers arises from the requirement for programmes to study samples of objects of statistically significant size, in large-scale unbiased surveys of galactic and extra-galactic regions. Along with morphological information, the new spectral imaging system can be used to study the physical and chemical properties of regions of interest. Its three-dimensional imaging capabilities are critical for research into turbulence and dynamics. In addition, HARP/ACSIS will provide highly complementary science programmes to wide-field continuum studies, and produce the essential preparatory work for submillimetre interferometers such as the SMA and ALMA.Comment: MNRAS Accepted 2009 July 2. 18 pages, 25 figures and 6 table

Educating a New Generation of Doctors to Improve the Health of Populations in Low- and Middle-Income Countries

Francesca Celletti and colleagues from WHO argue that a transformation in the scale-up of medical education in low- and middle-income countries is needed, and detail what this might look like

Impact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation

Pre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy