Shared Ageing Research Models (ShARM) : a new facility to support ageing research

In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing. However, the time and cost needed to rear aged cohorts can limit research opportunities. Sharing of resources can provide an ethically and economically superior framework to overcome some of these issues but requires dedicated infrastructure. Shared Ageing Research Models (ShARM) (www.ShARMUK.org) is a new, not-for-profit organisation funded by Wellcome Trust, open to all investigators. It collects, stores and distributes flash frozen tissues from aged murine models through its biorepository and provides a database of live ageing mouse colonies available in the UK and abroad. It also has an online environment (MICEspace) for collation and analysis of data from communal models and discussion boards on subjects such as the welfare of ageing animals and common endpoints for intervention studies. Since launching in July 2012, thanks to the generosity of researchers in UK and Europe, ShARM has collected more than 2,500 tissues and has in excess of 2,000 mice registered in live ageing colonies. By providing the appropriate support, ShARM has been able to bring together the knowledge and experience of investigators in the UK and Europe to maximise research outputs with little additional cost and minimising animal use in order to facilitate progress in ageing research

Disease-specific, neurosphere-derived cells as models for brain disorders

There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery

Electron momentum distribution in underdoped cuprates

We investigate the electron momentum distribution function (EMD) in a weakly doped two-dimensional quantum antiferromagnet (AFM) as described by the t-J model. Our analytical results for a single hole in an AFM based on the self-consistent Born approximation (SCBA) indicate an anomalous momentum dependence of EMD showing 'hole pockets' coexisting with a signature of an emerging large Fermi surface. The position of the incipient Fermi surface and the structure of the EMD is determined by the momentum of the ground state. Our analysis shows that this result remains robust in the presence of next-nearest neighbor hopping terms in the model. Exact diagonalization results for small clusters are with the SCBA reproduced quantitatively.Comment: 5 pages, submitted to PR

Superconducting gap in the presence of bilayer splitting in underdoped Bi(Pb)2212

The clearly resolved bilayer splitting in ARPES spectra of the underdoped Pb-Bi2212 compound rises the question of how the bonding and antibonding sheets of the Fermi surface are gapped in the superconducting state. Here we compare the superconducting gaps for both split components and show that within the experimental uncertainties they are identical. By tuning the relative intensity of the bonding and antibonding bands using different excitation conditions we determine the precise {\bf k}-dependence of the leading edge gap. Significant deviations from the simple cos($k_{x}$)-cos($k_{y}$) gap function for the studied doping level are detected.Comment: 5 pages, 4 figures (revtex4

Fully Gapped Single-Particle Excitations in the Lightly Doped Cuprates

The low-energy excitations of the lightly doped cuprates were studied by angle-resolved photoemission spectroscopy. A finite gap was measured over the entire Brillouin zone, including along the d_{x^2 - y^2} nodal line. This effect was observed to be generic to the normal states of numerous cuprates, including hole-doped La_{2-x}Sr_{x}CuO_{4} and Ca_{2-x}Na_{x}CuO_{2}Cl_{2} and electron-doped Nd_{2-x}Ce_{x}CuO_{4}. In all compounds, the gap appears to close with increasing carrier doping. We consider various scenarios to explain our results, including the possible effects of chemical disorder, electronic inhomogeneity, and a competing phase.Comment: To appear in Phys. Rev.

New Strings for Old Veneziano Amplitudes III. Symplectic Treatment

A d-dimensional rational polytope P is a polytope whose vertices are located at the nodes of d-dimensional Z-lattice. Consider a number of points inside the inflated polytope (with coefficient of inflation k, k=1,2, 3...). The Ehrhart polynomial of P counts the number of such lattice points (nodes) inside the inflated P and (may be) at its faces (including vertices). In Part I (hep-th/0410242) of our four parts work we noticed that the Veneziano amplitude is just the Laplace transform of the generating function (considered as a partition function in the sence of statistical mechanics) for the Ehrhart polynomial for the regular inflated simplex obtained as a deformation retract of the Fermat (hyper) surface living in complex projective space. This observation is sufficient for development of new symplectic (this work) and supersymmetric (hep-th/0411241)physical models reproducing the Veneziano (and Veneziano-like) amplitudes. General ideas (e.g.those related to the properties of Ehrhart polynomials) are illustrated by simple practical examples (e.g. use of mirror symmetry for explanation of available experimental data on pion-pion scattering) worked out in some detail. Obtained final results are in formal accord with those earlier obtained by Vergne [PNAS 93 (1996) 14238].Comment: 48 pages J.Geom.Phys.(in press, available on line

Holes in the t-J_z model: a thorough study

The t-J_z model is the strongly anisotropic limit of the t-J model which captures some general properties of the doped antiferromagnets (AF). The absence of spin fluctuations simplifies the analytical treatment of hole motion in an AF background and allows us to calculate the single- and two-hole spectra with high accuracy using regular diagram technique combined with real-space approach. At the same time, numerical studies of this model via exact diagonalization (ED) on small clusters show negligible finite size effects for a number of quantities, thus allowing a direct comparison between analytical and numerical results. Both approaches demonstrate that the holes have tendency to pair in the p- and d-wave channels at realistic values of t/J. The interactions leading to pairing and effects selecting p and d waves are thoroughly investigated. The role of transverse spin fluctuations is considered using perturbation theory. Based on the results of the present study, we discuss the pairing problem in the realistic t-J-like model. Possible implications for preformed pairs formation and phase separation are drawn.Comment: 21 pages, 15 figure

New strings for old Veneziano amplitudes II. Group-theoretic treatment

In this part of our four parts work (e.g see Part I, hep-th/0410242) we use the theory of polynomial invariants of finite pseudo-reflection groups in order to reconstruct both the Veneziano and Veneziano-like (tachyon-free) amplitudes and the generating function reproducing these amplitudes. We demonstrate that such generating function can be recovered with help of the finite dimensional exactly solvable N=2 supersymmetric quantum mechanical model known earlier from works by Witten, Stone and others. Using the Lefschetz isomorphisms theorem we replace traditional supersymmetric calculations by the group-theoretic thus solving the Veneziano model exactly using standard methods of representation theory. Mathematical correctness of our arguments relies on important theorems by Shepard and Todd, Serre and Solomon proven respectively in early fifties and sixties and documented in the monograph by Bourbaki. Based on these theorems we explain why the developed formalism leaves all known results of conformal field theories unchanged. We also explain why these theorems impose stringent requirements connecting analytical properties of scattering amplitudes with symmetries of space-time in which such amplitudes act.Comment: 57 pages J.Geom.Phys.(in press, available on line

Functional associations of pleuroparenchymal fibroelastosis and emphysema with hypersensitivity pneumonitis

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has been described in hypersensitivity pneumonitis (HP) yet its functional implications are unclear. Combined pulmonary fibrosis and emphysema (CPFE) has occasionally been described in never-smokers with HP, but epidemiological data regarding its prevalence is sparse. CTs in a large HP cohort were therefore examined to identify the prevalence and effects of PPFE and emphysema. Methods: 233 HP patients had CT extents of interstitial lung disease (ILD) and emphysema quantified to the nearest 5%. Lobar percentage pleural involvement of PPFE was quantified on a 4-point categorical scale: 0 = absent, 1 = affecting 33%. Marked PPFE reflected a total lung score of ≥3/18. Results were evaluated against FVC, DLco and mortality. RESULTS: Marked PPFE prevalence was 23% whilst 23% of never-smokers had emphysema. Following adjustment for patient age, gender, smoking status, and ILD and emphysema extents, marked PPFE independently linked to reduced baseline FVC (p = 0.0002) and DLco (p = 0.002) and when examined alongside the same covariates, independently linked to worsened survival (p = 0.01). CPFE in HP demonstrated a characteristic functional profile of artificial lung volume preservation and disproportionate DLco reduction. CPFE did not demonstrate a worsened outcome when compared to HP patients without emphysema beyond that explained by CT extents of ILD and emphysema. CONCLUSIONS: PPFE is not uncommon in HP, and is independently associated with impaired lung function and increased mortality. Emphysema was identified in 23% of HP never-smokers. CPFE appears not to link to a malignant microvascular phenotype as outcome is explained by ILD and emphysema extents

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results