Alzheimer's disease and age-related macular degeneration have different genetic models for complement gene variation

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.

Electron refluxing and K-shell line emission from Ti foils irradiated with sub-picosecond laser pulses at 527nm

We present data on emission of K-shell radiation from Ti foils irradiated with subpicosecond pulses of second harmonic radiation (527 nm) from the TARANIS laser system at intensities of up to 1018 Wcm-2. The data are used to demonstrate that a resonance absorption type mechanism is responsible for absorption of the laser light and to estimate fast electron temperatures of 30–60 keV that are in broad agreement with expectation from models of absorption for a steep density gradient. Data taken with resin-backed targets are used to demonstrate clear evidence of electron refluxing even at the modest fast electron temperatures inferred.

On Quillen's calculation of graded K-theory

We adapt Quillen’s calculation of graded K-groups of Z-graded rings with support in N to graded K-theory, allowing gradings in a product Z×G with G an arbitrary group. This in turn allows us to use induction and calculate graded K-theory of Z -multigraded rings.

Functional expression of KCNQ (Kv7) channels in guinea-pig bladder smooth muscle and their contribution to spontaneous activity

Background and Purpose: The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility. 

Experimental Approach: KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors. 

Key Results: KCNQ subtypes 1-5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20M) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity. 

Conclusions and Implications: These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder.

Optimisation and scaling of interfacial GeO2 layers for high-k gate stacks on germanium and extraction of dielectric constant of GeO2

Germanium is an attractive channel material for MOSFETs because of its higher mobility than silicon. In this paper, GeO2 has been investigated as an interfacial layer for high-kappa gate stacks on germanium. Thermally grown GeO2 layers have been prepared at 550 degrees C to minimise GeO volatilisation. GeO2 growth has been performed in both pure O-2 ambient and O-2 diluted with N-2. GeO2 thickness has been scaled down to approximately 3 nm. MOS capacitors have been fabricated using different GeO2 thicknesses with a standard high-kappa dielectric on top. Electrical properties and thermal stability have been tested up to at least 350 degrees C. The K value of GeO2 was experimentally determined to be 4.5. Interface state densities (D-it) of less than 10(12) CM-2 eV(-1) have been extracted for all devices using the conductance method.

Irresponsible Lending?: A Case Study of a U.K. Credit Industry Reform Initiative

There are major concerns about the level of personal borrowing, particularly sourced from credit cards. This paper charts the progress of an initiative to create a Responsible Lending Index (RLI) for the credit industry. The RLI proposed to voluntarily benchmark lending standards and promote best practice within the credit industry by involving suppliers of credit, customer representatives and regulators. However, despite initial support from some banks, consumer bodies and the Chair of the Treasury Select Committee, it failed to gain sufficient support from financial institutions in its original format. The primary reasons for this were related to the complexity of building such a robust index and the banks trade body’s fear of exposing its members to public scrutiny. A revised alternative, the Responsible Lending Initiative, was proposed which took into account these concerns. However, the Association of Payment Clearing Service (APACS), the trade body of the credit industry, then effectively destroyed the proposal. This article describes an attempt to address the challenges in the credit card industry with the initiation of the RLI, reflected in stakeholder discourse and in the context of a wider concern expressed by the involved stakeholders in terms of the need for greater responsibility in the banking industry’s lending practices.

Thermal conductivities of ionic liquids over the temperature range from 293 K to 353 K

The thermal conductivities of 11 ionic liquids were determined, over the temperature range from 293 K to 353 K, at atmospheric pressure, using an apparatus based on the transient hot-wire method. For each of the ionic liquids studied, the thermal conductivities were found to be between (0.1 and 0.2) W.m(-1).K-1, with a slight decrease observed on increasing temperature. The uncertainty is estimated to be less than +/- 0.002 W.m(-1).K-1. In all cases, a linear equation was found to give a good fit to the data. The effects of water content and chloride content on the thermal conductivities of some of the ionic liquids were investigated. In each case, the thermal conductivities of the water + ionic liquid and chloride + ionic liquid binary mixtures were found to be less than the weighted average of the pure component thermal conductivities. This effect was adequately modeled using the Jamieson correlation. Chloride contamination at typical postsynthesis levels was found to have no significant effect on the thermal conductivities of the ionic liquid studied.

Law, Politics and Financial Development: The Great Reversal of the U.K. Corporate Debt Market

This article examines the role of creditor protection in the development of the U.K. corporate bond market. This market grew rapidly in the late nineteenth century, but in the twentieth century it experienced a reversal, albeit with a short-lived post-1945 renaissance. Such was the extent of the reversal that the market from the 1970s onwards was smaller than it had been in 1870. We find that law does not explain the variation in the size of this market over time. Alternatively, our evidence suggests that inflation and taxation policies were major drivers of this market in the post-1945 era. Copyright © The Economic History Association 2013

Preliminary Report of the 1 field season at Gubbio.:Malone, C.A.T. and S.K.F. Stoddart,

Xerox circulation to sponsors. Cambridge University.

Review of: Tykot, R.H. and Andrews, T.K. 1992. Sardinia: a footprint in the sea: studies in Sardinian Archaeology presented to Miriam Balmuth. Sheffield Academic Press

Proceedings of the Prehistoric Society, 1994. 60: p. 455-6.

A randomised control trial evaluation of a literacy after-school programme for struggling beginning readers

While there is evidence for effective in-school programmes
for struggling beginning readers, the evidence in relation to after-schools
interventions focusing on academic outcomes is particularly weak. This study
seeks to contribute to this body of evidence through a randomized trial (n=464)
of an after-school literacy programme (DoodleDen) for struggling beginning readers in a deprived area of Dublin, Ireland.

The programme based on a balanced literacy framework, was delivered in group
settings, and had a strong focus on staff development. Doodle Den was found to improve the children’s overall literacy (d=+0.17), teacher assessments of their literacy ability (d=+0.28) and to positively impact on problem behaviours in regular school class (d=-0.18). The implications for
the development of after-school programmes are discussed.

Common variant at 16p11.2 conferring risk of psychosis

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association (GWA) study, meta-analysis and follow-up (totaling as many as 18,206 cases and 42,536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7,469 bipolar disorder cases, 1,535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46,160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T], OR = 1.08, P = 6.6 × 10−11). The new variant is located within a 593 kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium dataset; P = 0.00047 in 22,651 additional Icelanders).

The Next Generation Transit Survey (NGTS)

The Next Generation Transit Survey (NGTS) is a new ground-based sky survey designed to find transiting Neptunes and super-Earths. By covering at least sixteen times the sky area of Kepler we will find small planets around stars that are sufficiently bright for radial velocity confirmation, mass determination and atmospheric characterisation. The NGTS instrument will consist of an array of twelve independently pointed 20cm telescopes fitted with red-sensitive CCD cameras. It will be constructed at the ESO Paranal Observatory, thereby benefiting from the very best photometric conditions as well as follow up synergy with the VLT and E-ELT. Our design has been verified through the operation of two prototype instruments, demonstrating white noise characteristics to sub-mmag photometric precision. Detailed simulations show that about thirty bright super-Earths and up to two hundred Neptunes could be discovered. Our science operations are due to begin in 2014.