Avandia (TM) - From molecule to market for type 2 diabetes.

Type 2 diabetes is a disease fast approaching epidemic proportions throughout the world. From insulin sensitizers to PPARg agonists, the lecture will outline the successful medicinal chem. and biol. strategy underpinning the discovery and selection of Avandia, an innovative new medicine for this disease.

In vitro testing of Advanced JAX (TM) Bone Void Filler System: species differences in the response of bone marrow stromal cells to beta tri-calcium phosphate and carboxymethylcellulose gel

The Advanced JAX (TM) Bone Void Filler System (AJBVFS) is a novel bone graft material manufactured by Smith and Nephew Orthopaedics Ltd. and comprises beta tri-calcium phosphate granules with carboxymethylcellulose (CMC) gel as a handling agent. This study investigated the potential, in vitro, of the AJBVFS to function as a delivery system for cell therapy to enhance healing of bone defects. The attachment of rabbit bone marrow stromal cells (rbBMSCs), human BMSCs (hBMSCs) and human bone-derived cells (hBDCs) to JAX (TM) granules and the effect of CMC gel on cell proliferation and differentiation were investigated. There were slight species differences in the number and morphology of cells attached on the JAX (TM) granules with less rbBMSC attachment than human. All cells tolerated the presence of CMC gel and a reduction in cell number was only seen after longer exposure to higher gel concentrations. Low concentrations of CMC gel enhanced proliferation, alkaline phosphatase (ALP) expression and ALP activity in human cells but had no effect on rbBMSC. This study suggests that AJBVFS is an appropriate scaffold for the delivery of osteogenic cells and the addition of CMC gel as a handling agent promotes osteogenic proliferation and differentiation and is therefore likely to encourage bone healing.

WASP-50 b: a hot Jupiter transiting a moderately active solar-type star

We report the discovery by the WASP transit survey of a giant planet in a close orbit (0.0295 ± 0.0009 AU) around a moderately bright (V = 11.6, K = 10) G9 dwarf (0.89 ± 0.08 Msun, 0.84 ± 0.03 Rsun) in the Southern constellation Eridanus. Thanks to high-precision follow-up photometry and spectroscopy obtained by the telescopes TRAPPIST and Euler, the mass and size of this planet, WASP-50 b, are well constrained to 1.47 ± 0.09 MJup and 1.15 ± 0.05 RJup, respectively. The transit ephemeris is 2 455 558.6120 (±0.0002) + N × 1.955096 (±0.000005) HJDUTC. The size of the planet is consistent with basic models of irradiated giant planets. The chromospheric activity (log R'HK = -4.67) and rotational period (Prot = 16.3 ± 0.5 days) of the host star suggest an age of 0.8 ± 0.4 Gy that is discrepant with a stellar-evolution estimate based on the measured stellar parameters (?* = 1.48 ± 0.10 ?sun, Teff = 5400 ± 100 K, [Fe/H] = -0.12 ± 0.08) which favors an age of 7 ± 3.5 Gy. This discrepancy could be explained by the tidal and magnetic influence of the planet on the star, in good agreement with the observations that stars hosting hot Jupiters tend to show faster rotation and magnetic activity. We measure a stellar inclination of 84-31+6 deg, disfavoring a high stellar obliquity. Thanks to its large irradiation and the relatively small size of its host star, WASP-50 b is a good target for occultation spectrophotometry, making it able to constrain the relationship between hot Jupiters' atmospheric thermal profiles and the chromospheric activity of their host stars. The photometric time-series used in this work are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/533/A88

Characterisation of the photocatalyst Pilkington Activ (TM): a reference film photocatalyst?

Pilkington Glass Activ(TM) represents a possible suitable successor to P25 TiO2, especially as a benchmark photocatalyst film for comparing other photocatalyst or PSH self-cleaning films. Activ(TM) is a glass product with a clear, colourless, effectively invisible, photocatalytic coating of titania that also exhibits PSH. Although not as active as a film of P25 TiO2, Activ(TM) vastly superior mechanical stability, very reproducible activity and widespread commercial availability makes it highly attractive as a reference photocatalytic film. The photocatalytic and photo-induced superhydrophilitic (PSH) properties of Activ(TM) are studied in some detail and the results reported. Thus, the kinetics of stearic acid destruction (a 104 electron process) are zero order over the stearic acid range 4-129 monolayers and exhibit formal quantum efficiencies (FQE) of 0.7 X 10(-5) and 10.2 x 10(-5) molecules per photon when irradiated with light of 365 +/- 20 and 254 nm, respectively; the latter appears also to be the quantum yield for Activ(TM) at 254 nm. The kinetics of stearic acid destruction exhibit Langmuir-Hinshelwood-like saturation type kinetics as a function of oxygen partial pressure, with no destruction occurring in the absence of oxygen and the rate of destruction appearing the same in air and oxygen atmospheres. Further kinetic work revealed a Langmuir adsorption type constant for oxygen of 0.45 +/- 0.16 kPa(-1) and an activation energy of 19 +/- 1 Kj mol(-1). A study of the PSH properties of Activ(TM) reveals a high water contact angle (67) before ultra-bandgap irradiation reduced to 0degrees after prolonged irradiation. The kinetics of PSH are similar to those reported by others for sol-gel films using a low level of UV light. The kinetics of contact angle recovery in the dark appear monophasic and different to the biphasic kinetics reported recently by others for sol-gel films [J. Phys. Chem. B 107 (2003) 1028]. Overall, Activ(TM) appears a very suitable reference material for semiconductor film photocatalysis. (C) 2003 Elsevier Science B.V All rights reserved.

A 50,000-year record of Late Pleistocene tropical vegetation and human impact in lowland Borneo.

There has been considerable uncertainty about the nature of Pleistocene environments colonised by the first modern humans in Island SE Asia, and about the vegetation of the Last Glacial Maximum (LGM) in the region. Here, the palynology from a series of exposures in the Great Cave of Niah, Sarawak, Malaysian Borneo, spanning a period from ca. 52,000 to 5000 BP is described. Vegetation during this period was climate-driven and often highly unstable. Interstadials are marked by lowland forest, sometimes rather dry and at times by mangroves. Stadials are indicated by taxa characteristic of open environments or, as at the LGM, by highly disturbed rather open forest. Stadials are also characterised by taxa now restricted to 1000-1600 m above sea level, suggesting temperature declines of ca 7-9 C relative to present, by comparison with modern lapse rates. The practice of biomass burning appears associated with the earliest human activity in the cave.