GAD65 Autoantibody Responses in Japanese Latent Autoimmune Diabetes in Adult Patients

OBJECTIVE—To determine whether development of insulin requirement in patients with latent autoimmune diabetes in adults (LADA) is accompanied with the emergence of a type 1 diabetes–like autoimmune response

On-Chip Tests for the Characterization of the Mechanical Strength of Polysilicon †

Microelectromechanical systems (MEMS) are nowadays widespread in the sensor market, with several different applications. New production techniques and ever smaller device geometries require a continuous investigation of potential failure mechanisms in such devices. This work presents an experimental on-chip setup to assess the geometry- and material-dependent strength of stoppers adopted to limit the deformation of movable parts, using an electrostatically actuated device. A series of comb-finger and parallel plate capacitors are used to provide a rather large stroke to a shuttle, connected to the anchors through flexible springs. Upon application of a varying voltage, failure of stoppers of variable size is observed and confirmed by post-mortem DC–V curves. The results of the experimental campaign are collected to infer the stochastic property of the strength of polycrystalline, columnar silicon films

Towards a definition of a real-time forecasting network for rainfall induced shallow landslides

PREVIEW is an European Commission FP6 Integrated Project with the aim of developing, at an European level, innovative geo-information services for atmospheric, geophysical and man-made risks. Within this framework, the Landslides Platform Service 2 (forecasting of shallow rapid slope movements) has developed an integrated procedure for the forecasting and warning of distributed shallow landsliding to be used for civil protection purposes. The Service consists of an automated end-to-end forecasting chain which uses data from a probabilistic downscaled short-term rainfall forecast, soil saturation estimates and meteorological radar outputs. The above data are entered into a hydro-geological model that makes use of an infinite slope approach to calculate the distributed Factor of Safety over the entire basin. All outputs, and much of the input data, are shown on a WebGIS system so that end-users can interactively access and download data. A distinctive feature of the service is the use of an innovative soil depth model for predicting the distributed thickness of the regolith cover within the basin, which is one of the most important parameters controlling shallow landslide triggering. The service was developed in a pilot test site in NE Italy, the Armea basin. Validation makes use of two rainfall events: one that occurred in 2000 and a smaller, more recent event (2006) that caused fewer landslides. Rainfall data have been used to compute a distributed factor-of-safety map that has been overlaid onto the landslide inventory. Instead of a traditional validation approach based on the number count of correctly identified landslides, we carried out an alternative procedure based on the landslides area that gave outcomes which, for this preliminary stage of the research, can be considered promising

Conformation-dependent GAD65 autoantibodies in diabetes

Aims/hypothesis. Conformation-dependent autoantibodies directed against GAD65 are markers of Type 1 diabetes. In this study we aimed to determine whether the substitution of GAD65 with GAD67 amino acids would affect the binding of conformation-dependent GAD65 autoantibodies. Methods. We used PCR-based site-directed mutagenesis to generate a series of mutated GAD65 cDNA constructs in which specific GAD65 coding sequences for regions of the protein critical for autoantibody binding were replaced with GAD67 coding sequences. Results. The introduction of a point mutation at position 517, substituting glutamic acid with proline, markedly reduced the binding of disease-associated GAD65 antibodies. The binding of GAD65 antibodies to the E517P mutant was reduced in the sera of all newly diagnosed Type 1 diabetes patients (n=85) by a mean of 72% (p<0.0001) compared with binding to wild-type GAD65. Patients with latent autoimmune diabetes in adults (n=24) showed a similar reduction in binding (79% reduction, p<0.0001). First-degree relatives who subsequently progressed to Type 1 diabetes (n=12) showed a reduction in binding of 80% compared with a reduction of only 65% among relatives who had not progressed to disease (n=38; p=0.025). In healthy GAD65Ab-positive individuals who did not progress to diabetes during a 9-year follow-up period (n=51), binding to GAD65-E517P was reduced by only 28% compared with binding to wild-type GAD65. Conclusions/interpretation. Differences in autoantibody binding to wild-type GAD65 versus GAD65-E517P may provide predictive information about Type 1 diabetes risk beyond that provided by the presence or absence of GAD65 autoantibodies. Lack of binding to mutant GAD65-E517P defines GAD65-positive individuals who are at higher risk of developing diabetes