Calculating the Prepotential by Localization on the Moduli Space of Instantons

We describe a new technique for calculating instanton effects in supersymmetric gauge theories applicable on the Higgs or Coulomb branches. In these situations the instantons are constrained and a potential is generated on the instanton moduli space. Due to existence of a nilpotent fermionic symmetry the resulting integral over the instanton moduli space localizes on the critical points of the potential. Using this technology we calculate the one- and two-instanton contributions to the prepotential of SU(N) gauge theory with N=2 supersymmetry and show how the localization approach yields the prediction extracted from the Seiberg-Witten curve. The technique appears to extend to arbitrary instanton number in a tractable way.Comment: 24 pages, JHEP.cls, more references and extra discussion on N_F=2N cas

Inflation with Non-minimal Gravitational Couplings and Supergravity

We explore in the supergravity context the possibility that a Higgs scalar may drive inflation via a non-minimal coupling to gravity characterised by a large dimensionless coupling constant. We find that this scenario is not compatible with the MSSM, but that adding a singlet field (NMSSM, or a variant thereof) can very naturally give rise to slow-roll inflation. The inflaton is necessarily contained in the doublet Higgs sector and occurs in the D-flat direction of the two Higgs doublets.Comment: 13 pages, 1 figur

The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil

Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection

M1 muscarinic allosteric modulators slow prion neurodegeneration and restore memory loss.

The current frontline symptomatic treatment for Alzheimer's disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR-selective orthosteric ligands has proven challenging. Here, we have shown that mouse prion disease shows many of the hallmarks of human AD, including progressive terminal neurodegeneration and memory deficits due to a disruption of hippocampal cholinergic innervation. The fact that we also show that muscarinic signaling is maintained in both AD and mouse prion disease points to the latter as an excellent model for testing the efficacy of muscarinic pharmacological entities. The memory deficits we observed in mouse prion disease were completely restored by treatment with benzyl quinolone carboxylic acid (BQCA) and benzoquinazoline-12 (BQZ-12), two highly selective positive allosteric modulators (PAMs) of M1 mAChRs. Furthermore, prolonged exposure to BQCA markedly extended the lifespan of diseased mice. Thus, enhancing hippocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of mouse prion disease, indicating that this ligand type may have clinical benefit in diseases showing defective cholinergic transmission, such as AD

Parchment degradation analyzed by X-ray diffraction

Many important historical events have occured in ancient Israel. A huge amount of material signs of civilization has been excavated and studied and the bio- as well as material culture has shed light on how the ancients lived, what they did to stay alive, and what were the reasons they became ill and died. One of the most important gifts that has come to us just by an accidental find are the Dead Sea Scrolls that are the backbone for exploring the oral tradition between the spiritual writings of 2000 years ago and what is known today as the "Bible". The Dead Sea Scrolls are the focus of the Qumran Project and the scientific research has started to illuminate the background of these manuscripts. This volume summarises the presentations given at a meeting held at the Hebrew University in Jerusalem (Israel) in 2005. The Qumran Project is part of COST Action G8, entitled "Non-destructive analysis and testing of museum objects". G8 represents an European network fostering interdisciplinary cooperation to improve the preservation and conservation of our cultural heritage by increasing the information on museum objects through non-destructive analysis and testing. Action G8 and those proceedings have been supported by COST, an intergovernmental European framework that allows the coordination of nationally funded research at a pan-European level (see: www.cost.esf.org)

Measuring crystallinity of laser cleaned silk by X-ray diffraction

We present an effective and sensitive method of analyzing the condition of silk following laser cleaning. New silk samples were analysed; two sets were soiled with carbon black before laser cleaning and two sets were left unsoiled. Samples were exposed to laser cleaning at a wavelength of 532 nm and a fluence of 1.5 J/cm2 for 4, 16 and 64 pulses. Two sample sets were also treated at fluence levels of 0.5, 1.0 and 4.2 J/cm2 to assess the effects of fluence on the silk structure. Wide angle X-ray diffraction was carried out using the NanoSTAR facility at Cardiff University. Using the main equatorial reflections from silk the crystallinity of the samples was calculated. Upon laser cleaning at 1.5 J/cm2, the silk displayed a reduced level of crystallinity as the number of pulses increased, with soiled silks displaying a greater crystallinity loss than unsoiled silks. Coupled with this, the crystal size, as analysed using the Scherrer formula, was shown to increase as the crystallinity reduced. The effects of fluence on the sample crystallinity was less obvious: samples treated at 0.5 J/cm2 displayed an intrinsically higher crystallinity than all other samples, but there was no progressive loss of crystallinity with increasing fluence level as may have been anticipated

X-ray diffraction study into the effects of liming on the structure of collagen

The manufacture of parchment from animal skin involves processes that remove hair, fats, and other macromolecules. Although it is well understood that the collagen fibers "open up" during processing, this study uses small and wide-angle X-ray diffraction to measure quantitatively the changes induced at the nanoscopic and microscopic levels. The axial rise per residue distance within the collagen molecules is unaffected by salt and lime treatments. Salting of the hides appears to remove noncollagenous materials. The intermolecular lateral packing distance between the hydrated collagen molecules (1.4 nm) increases after salting (~1.5 nm) and liming (~1.55 nm); drying is responsible for a reduction to ~1.2 nm in all samples. The axial staggered array (d spacing) is reduced by 1 nm after liming and is unaffected by drying. The average fibril diameter increases from 103.2 to 114.5 nm following liming, and the fibril-to-fibril distance increases from 122.6 to 136.1 nm. © 2006 American Chemical Society