Positive allosteric modulators of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor

L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a fundamental role in the control of motor function, cognition and mood. The physiological effects of glutamate are mediated through two functionally distinct receptor families. While activation of metabotropic (G-protein coupled) glutamate receptors results in modulation of neuronal excitability and transmission, the ionotropic glutamate receptors (ligand-gated ion channels) are responsible for mediating the fast synaptic response to extracellular glutamate

Spectrometry: Report of panel

Spectroscopic measurements are required to define the spectral background and provide the detailed spectral information that is essential for the design of species-specific systems and the analysis of data obtained from them. This function of spectroscopic measurements is expected to be an important part of any tropospheric remote-sensing program, and both emission and absorption spectroscopy are relevant in this context. The data from such observations are of value to tropospheric science in their own right, during the initial phases while species-specific techniques and instruments are under development. In addition, there are a number of unresolved problems in tropospheric radiative transfer and spectroscopy which presently limit the accuracy and reliability of all remote sensing methods. Only through a supporting program of spectroscopic measurements can progress be made in improving the understanding of these aspects of radiative transfer and ultimately reaching the desired confidence in the accuracy to species-specific monitoring techniques

A novel series of positive modulators of the AMPA receptor : discovery and structure based hit-to-lead studies

Starting from an HTS derived hit 1, application of biostructural data facilitated rapid optimization to lead 22, a novel AMPA receptor modulator. This is the first demonstration of how structure based drug design can be exploited in an optimization program for a glutamate receptor

Hydrothermal Chimney Distribution on the Endeavour Segment, Juan de Fuca Ridge

The Endeavour Segment of the Juan de Fuca Ridge is well known for its abundance of hydrothermal vents and chimneys. One‐meter scale multibeam mapping data collected by an autonomous undersea vehicle revealed 572 chimneys along the central 14 km of the segment, although only 47 are named and known to be active. Hydrothermal deposits are restricted to the axial graben and the near‐rims of the graben above a seismically mapped axial magma lens. The sparse eruptive activity on the segment during the last 4,300 years has not buried inactive chimneys, as occurs at more magmatically robust mid‐ocean ridges

Hydrothermal Chimney Distribution on the Endeavour Segment, Juan de Fuca Ridge

The Endeavour Segment of the Juan de Fuca Ridge is well known for its abundance of hydrothermal vents and chimneys. One-meter scale multibeam mapping data collected by an autonomous undersea vehicle revealed 572 chimneys along the central 14 km of the segment, although only 47 are named and known to be active. Hydrothermal deposits are restricted to the axial graben and the near-rims of the graben above a seismically mapped axial magma lens. The sparse eruptive activity on the segment during the last 4,300 years has not buried inactive chimneys, as occurs at more magmatically robust mid-ocean ridges

Bioactive sol-gel glasses at the atomic scale: the complementary use of advanced probe and computer modelling methods

Sol-gel synthesised bioactive glasses may be formed via a hydrolysis condensation reaction, silica being introduced in the form of tetraethyl orthosilicate (TEOS) and calcium is typically added in the form of calcium nitrate. The synthesis reaction proceeds in an aqueous environment; the resultant gel is dried, before stabilisation by heat treatment. These materials, being amorphous, are complex at the level of their atomic-scale structure, but their bulk properties may only be properly understood on the basis of that structural insight. Thus, a full understanding of their structure : property relationship may only be achieved through the application of a coherent suite of leading-edge experimental probes, coupled with the cogent use of advanced computer simulation methods. Using as an exemplar a calcia-silica sol-gel glass of the kind developed by Larry Hench, to whose memory this paper is dedicated, we illustrate the successful use of high-energy x-ray and neutron scattering (diffraction) methods, magic-angle spinning solid state NMR, and molecular dynamics simulation as components to a powerful methodology for the study of amorphous materials

Frailty of Māori, Pasifika, and non-Māori/non-Pasifika older people in New Zealand: a national population study of older people referred for home care services

Little is known about the prevalence of frailty in indigenous populations. We developed a frailty index for older New Zealand Māori and Pasifika who require publicly funded support services.A frailty index (FI) was developed for New Zealand adults aged ≥65 years who had an interRAI-Home Care assessment between 1 June 2012 and 30 October 2015. A frailty score for each participant was calculated by summing the number of deficits recorded and dividing by the total number of possible deficits. This created a FI with a potential range from 0 to 1. Linear regression models for FIs with ethnicity were adjusted for age and sex. Cox proportional hazards models were used to assess the association between the FI and mortality for Māori, Pasifika, and non-Māori/non-Pasifika.Of 54,345 participants, 3,096 (5.7%) identified as Māori, 1,846 (3.4%) were Pasifika, and 49,415 (86.7%) identified as neither Māori nor Pasifika. New Zealand Europeans (48,178, 97.5%) constituted most of the latter group. Within each sex, the mean FIs for Māori and Pasifika were greater than the mean FIs for non-Māori and non-Pasifika, with the difference being more pronounced in females. The FI was associated with mortality (Māori SHR 2.53, 95% CI 1.63 to 3.95; Pasifika SHR 6.03, 95% CI 3.06 to 11.90; non-Māori and non-Pasifika SHR 2.86, 95% 2.53 to 3.25).This study demonstrated differences in FI between the ethnicities in this select cohort. After adjustment for age and sex, increases in FI were associated with increased mortality. This suggests that FI is predictive of poor outcomes in these ethnic groups