Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3) GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-diabetes.

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. Young adult ob/ob mice received once-daily intraperitoneal injections of saline vehicle or (Pro3)GIP over an 11-day period. Nonfasting plasma glucose levels and the overall glycemic excursion (area under the curve) to a glucose load were significantly reduced (1.6-fold; P <0.05) in (Pro3)GIP-treated mice compared with controls. GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P <0.05) and insulin (1.5-fold; P <0.05) responses to feeding. These changes were associated with significantly enhanced (1.6-fold; P <0.05) insulin sensitivity in the (Pro3)GIP-treated group. Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P <0.05) and partially corrected the obesity-related islet hypertrophy and ß-cell hyperplasia of ob/ob mice. These comprehensive beneficial effects of (Pro3)GIP were reversed 9 days after cessation of treatment and were independent of food intake and body weight, which were unchanged. These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes.

An investigation of the thermal stability and sulphur tolerance of Ag/Y-Al2O3 catalysts for the SCR of NOx with hydrocarbons and hydrogen

The sulphur tolerance and thermal stability of a 2 wt% Ag/gamma-Al2O3 catalyst was investigated for the H-2-promoted SCR of NO, with octane and toluene. The aged catalyst was characterised by XRD and EXAFS analysis. It was found that the effect of ageing was a function of the gas mix and temperature of ageing. At high temperatures (800 degrees C) the catalyst deactivated regardless of the reaction mix. EXAFS analysis showed that this was associated with the Ag particles on the surface of the catalyst becoming more ordered. At 600 and 700 degrees C, the deactivating effect of ageing was much less pronounced for the catalyst in the H-2-promoted octane-SCR reaction and ageing at 600 degrees C resulted in an enhancement in activity for the reaction in the absence of H-2. For the toluene + H-2-SCR reaction the catalyst deactivated at each ageing temperature. The effect of addition of low levels of sulphur (1 ppm SO2) to the feed was very much dependent on the reaction temperature. There was little deactivation of the catalyst at low temperatures ( 500 degrees C). The results can be explained by the activity of the catalyst for the oxidation Of SO2 to SO3 and the relative stability of silver and aluminium sulphates. The catalyst could be almost fully regenerated by a combination of heating and the presence of hydrogen in the regeneration mix. The catalyst could not be regenerated in the absence of hydrogen. (c) 2006 Published by Elsevier B.V.

Comparative evaluation of 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT) and 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)2H-tetrazolium, monosodium salt (WST-8) rapid colorimetric assays for antimicrobial susceptibility testing of staphylococci and ESBL-producing clinical isolates

A new generation of water soluble tetrazolium salts have recently become available and in this study we compared a colorimetric assay developed using one of these salts, 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8), with a previously developed 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide(XTT) colorimetric assay to determine which agent is most suitable for use as a colorimetric indicator in susceptibility testing. The MICs of 6 antibiotics were determined for 33 staphylococci using both colorimetric assays and compared with those obtained using the British Society for Antimicrobial Chemotherapy reference broth microdilution method. Absolute categorical agreement between the reference and test methods ranged from 79% (cefuroxime) to 100% (vancomycin) for both assays. No minor or major errors occurred using either assay with very major errors ranging from zero (vancomycin) to seven (cefuroxime). Analysis of the distribution of differences in the 1092 dilution MIC results revealed overall agreement, within the accuracy limits of the standard test ( 1 1092 dilution), using the XTT and WST-8 assays of 98% and 88%, respectively. Further studies on 31 ESBL-producing isolates were performed using the XTT method with absolute categorical agreement ranging from 87% (nitrofurantoin) to 100% (ofloxacin and meropenem). No errors were noted for either ofloxacin or meropenem with overall agreement of 91%. The data suggests that XTT is more reliable and accurate than WST-8 for use in a rapid antimicrobial susceptibility test. (c) 2007 Elsevier B.V. All rights reserved.

Sandstone response to salt weathering following simulated fire damage: a comparison of furnace heating and fire.

Fire has long been recognized as an agent of rock weathering. Our understanding of the impact of fire on stone comes either from early anecdotal evidence, or from more recent laboratory simulation studies, using furnaces to simulate the effects of fire. This paper suggests that knowledge derived from simulated heating experiments is based on the preconceptions of the experiment designer – when using a furnace to simulate fire, the operator decides on the maximum temperature and the duration of the experiment. These are key factors in determining the response of the stone to fire, and if these are removed from realworld observations then knowledge based on these simulations must be questioned. To explore the differences between heating sandstone in a furnace and a real fire, sample blocks of Peakmoor Sandstone were subjected to different stress histories in combination (lime rendering and removal, furnace heating or fire, frost and salt weathering). Block response to furnace heating and fire is discussed, with emphasis placed on the non-uniformity of the fire and of block response to fire in contrast to the uniform response to surface heating in a furnace. Subsequent response to salt weathering (by a 10% solution of sodium chloride and magnesium sulphate) was then monitored by weight loss. Blocks that had experienced fire showed a more unpredictable response to salt weathering than those that had undergone furnace heating – spalling of corners and rapid catastrophic weight loss were evidenced in blocks that had been subjected to fire, after periods of relative quiescence. An important physical side-effect of the fire was soot accumulation, which created a waxy, relatively impermeable layer on some blocks. This layer repelled water and hindered salt ingress, but eventually detached when salt, able to enter the substrate through more permeable areas, concentrated and crystallized behind it, resulting in rapid weight loss and accelerated decay. Copyright ©2007 John Wiley & Sons, Ltd.

High tolerance to gate misalignment in low voltage gate-underlap double gate MOSFETs

.In this letter, we demonstrate for the first time that gate misalignment is not a critical limiting factor for low voltage operation in gate-underlap double gate (DG) devices. Our results show that underlap architecture significantly extends the tolerable limit of gate misalignment in 25 nm devices. DG MOSFETs with high degree of gate misalignment and optimal gate-underlap design can perform comparably or even better than self-aligned nonunderlap devices. Results show that spacer-to-straggle (s/sigma) ratio, a key design parameter for underlap devices, should be within the range of 2.3-3.0 to accommodate back gate misalignment. These results are very significant as the stringent process control requirements for achieving self-alignment in nanoscale planar DG MOSFETs are considerably relaxed