Characterisation and glucoregulatory actions of a novel acylated form of the (Pro(3))GIP receptor antagonist in type 2 diabetes

In this study, we tested the biological activity of a novel acylated form of (Pro(3))glucose-dependent insulinotropic polypetide [(Pro3)GIP] prepared by conjugating palmitic acid to Lys(16) to enhance its efficacy in vivo by promoting binding to albumin and extending its biological actions. Like the parent molecule (Pro(3))GIP, (Pro(3))GIPLys(16)PAL was completely stable to the actions of DPP-IV and significantly (p <0.01 to p <0.001) inhibited GIP-stimulated cAMP production and cellular insulin secretion. Furthermore, acute administration of (Pro(3))GIPLys(16)PAL also significantly (p <0.05 to p <0.001) countered the glucose-lowering and insulin-releasing actions of GIP in ob/ob mice. Daily injection of (Pro(3))GIPLys(16)PAL (25 nmol/kg bw) in 14-18-week-old ob/ob mice over 14 days had no effect on body weight, food intake or non-fasting plasma glucose and insulin concentrations. (Pro(3))GIPLys(16)PAL treatment also failed to significantly alter the glycaemic response to an i.p. glucose load or test meal, but insulin concentrations were significantly reduced (1.5-fold; p <0.05) after the glucose load. Insulin sensitivity was enhanced (1.3-fold; p <0.05) and pancreatic insulin was significantly reduced (p <0.05) in the (Pro(3))GIPLys(16)PAL-treated mice. These data demonstrate that acylation of Lys(16) with palmitic acid in (Pro(3))GIP does not improve its biological effectiveness as a GIP receptor antagonist.

General trends in the barriers of catalytic reactions on transition metal surfaces

A catalyst preparation by design is one of the ultimate goals in chemistry. The first step towards this goal is to understand the origin of reaction barriers. In this study, we have investigated several catalytic reactions on some transition metal surfaces, using density functional theory. All the reaction barriers have been determined. By detailed analyses we obtain some insight into the reaction barrier. Each barrier is related to (i) the potential energy surface of reactants on the surface, (ii) the total chemisorption energy of reactants, and (iii) the metal d orbital occupancy and the reactant valency. (C) 2001 American Institute of Physics.

Improved Nonlinear PCA for Process Monitoring Using Support Vector Data Description

Nonlinear principal component analysis (PCA) based on neural networks has drawn significant attention as a monitoring tool for complex nonlinear processes, but there remains a difficulty with determining the optimal network topology. This paper exploits the advantages of the Fast Recursive Algorithm, where the number of nodes, the location of centres, and the weights between the hidden layer and the output layer can be identified simultaneously for the radial basis function (RBF) networks. The topology problem for the nonlinear PCA based on neural networks can thus be solved. Another problem with nonlinear PCA is that the derived nonlinear scores may not be statistically independent or follow a simple parametric distribution. This hinders its applications in process monitoring since the simplicity of applying predetermined probability distribution functions is lost. This paper proposes the use of a support vector data description and shows that transforming the nonlinear principal components into a feature space allows a simple statistical inference. Results from both simulated and industrial data confirm the efficacy of the proposed method for solving nonlinear principal component problems, compared with linear PCA and kernel PCA.

A Family Booklet About Comfort Care in Advanced Dementia:Three-Country Evaluation

Objectives: To evaluate a booklet on comfort care in dementia from the perspective of family with relevant experience, and assess nursing home resident and family factors associated with evaluations. Design: Retrospective study. Setting: Long term care facilities in French-speaking Canada, and the Netherlands and Italy.
Participants: Bereaved family (n = 138).
Measurements: An 8-item scale assessed the booklet's acceptability. Usefulness was rated on a 0 to 10 scale, and perceived usefulness referred to usefulness if family had had the booklet during the resident's stay. Families indicated preferred ways of obtaining, and the most appropriate time to get the booklet.
Results: Almost all families (94%) perceived the booklet as useful. Canadian and Dutch families evaluated the booklet's contents and format favorably, whereas Italian families' evaluations were less favorable. Almost all families endorsed roles for physicians or nurses and about half additionally accepted availability through own initiative, in print or through the Internet. Preference of timing was highly variable. Better acceptability, usefulness, and availability through own initiative were independently associated with non-Italian nationality, presence of more physical signs discussed in the booklet, feeling ill-prepared, and higher satisfaction with care. A preference of receiving the booklet early was more likely in Italian families, those without university education, and those involved with older residents.
Conclusion: The booklet is suitable to inform Dutch and Canadian families on comfort care in dementia, but implementation in Italy requires further consideration. The booklet may be integrated in advance care planning in long term care, and made available outside long term care settings to serve families who wish to be informed early. © 2012 American Medical Directors Association, Inc.
Keywords: Decision aid; decision making; advance care planning; palliative care; nursing homes; dementia.

Environmental Affordances and Children in Post-conflict Belfast

This paper examines the experiences of children in post-conflict Belfast as peace and social change afford new opportunities at the same time as they regulate behaviours and spatial practices. Theoretically and empirically it draws on the concept of environmental affordances in order to map the experiences of 11-year-old children in separate inner-city segregated and middle-class communities. Whilst the recession has affected the pace of urban restructuring, children in the expanding mixed and largely middleclass city extract multiple advantages from their area in ways not available to segregated communities. The paper concludes by highlighting the implications for effective listening strategies in the management of divided communities. © 2011 Taylor & Francis.

Derivation of Wave Loads for the Design of Oscillating Wave Surge Converters

This paper deals with the problem of estimating wave pressure loads acting on Oscillating Wave Surge Converters (OWSC) for assessment of fatigue on their components. Recent wave loading data issued from experimental testing of a 25th scale model of a box-shaped OWSC are here used to review the accuracy of the predictions made by an engineering method previously developed to derive wave pressure loads on OWSCs from experimental data. Predictions are shown underestimate wave pressure loads, and other methods subsequently developed are presented. A simplistic experimental method taking in consideration variations of the wetted surface area of the flap is shown to lead to relatively good estimates of wave pressure loads that could be used for fatigue calculations.

Time-dependent R-matrix theory applied to two-photon double ionization of He

We introduce a time-dependent R-matrix theory generalized to describe double-ionization processes. The method is used to investigate two-photon double ionization of He by intense XUV laser radiation. We combine a detailed B-spline-based wave-function description in an extended inner region with a single-electron outer region containing channels representing both single ionization and double ionization. A comparison of wave-function densities for different box sizes demonstrates that the flow between the two regions is described with excellent accuracy. The obtained two-photon double-ionization cross sections are in excellent agreement with other cross sections available. Compared to calculations fully contained within a finite inner region, the present calculations can be propagated over the time it takes the slowest electron to reach the boundary.