Abnormal cytoskeletal protein expression in cultured skin fibroblasts from type 1 diabetes mellitus patients with nephropathy: A proteomic approach

Diabetic nephropathy (DN) develops in about 40% of insulin-dependent type 1 diabetes mellitus (T1DM) patients, and is associated not only with diabetes duration and metabolic control, but also with a genetic predisposition. Constitutive alterations of cytoskeletal proteins may play a role in the development of DN. We investigated the expression of these proteins in cultured skin fibroblasts, obtained from long-term T1DM patients with and without DN but comparable metabolic control, and from matched healthy subjects, by means of 2-DE electrophoresis and MS-MALDI analyses. In T1DM with DN, compared to the other two groups, quantitative analyses revealed an altered expression of 17 spots (p<0.05-p<0.01), corresponding to 12 unique proteins. In T1DM with DN, beta-actin and three isoforms of tubulin beta-2 chain, tropomodulin-3, and LASP-1 were decreased, whereas two tubulin beta-4 chain isoforms, one alpha actinin-4 isoform, membrane-organizing extension spike protein (MOESIN), FLJ00279 (corresponding to a fragment of myosin heavy chain, non-muscle type A), vinculin, a tropomyosin isoform, and the macrophage capping protein were increased. A shift in caldesmon isoforms was also detected. These results demonstrate an association between DN and the constitutive expression of cytoskeleton proteins in cultured skin fibroblasts from T1DM with DN, which may retain pathophysiologycal implications.     

Combining supervised and unsupervised learning for data clustering

Clustering aims to partition a data set into homogenous groups which gather similar objects. Object similarity, or more often object dissimilarity, is usually expressed in terms of some distance function. This approach, however, is not viable when dissimilarity is conceptual rather than metric. In this paper, we propose to extract the dissimilarity relation directly from the available data. To this aim, we train a feedforward neural network with some pairs of points with known dissimilarity. Then, we use the dissimilarity measure generated by the network to guide a new unsupervised fuzzy relational clustering algorithm. An artificial data set and a real data set are used to show how the clustering algorithm based on the neural dissimilarity outperforms some widely used (possibly partially supervised) clustering algorithms based on spatial dissimilarity.     

Enhancing grid security by fine-grained behavioral control and negotiation-based authorization

Nowadays, Grid has become a leading technology in distributed computing. Grid poses a seamless sharing of heterogeneous computational resources belonging to different domains and conducts efficient collaborations between Grid users. The core Grid functionality defines computational services which allocate computational resources and execute applications submitted by Grid users. The vast models of collaborations and openness of Grid system require a secure, scalable, flexible and expressive authorization model to protect these computational services and Grid resources. Most of the existing authorization models for Grid have granularity to manage access to service invocations while behavioral monitoring of applications executed by these services remains a responsibility of a resource provider. The resource provider executes an application under a local account, and acknowledges all permissions granted to this account to the application. Such approach poses serious security threats to breach system functionality since applications submitted by users could be malicious. We propose a flexible and expressive policy-driven credential-based authorization system to protect Grid computational services against a malicious behavior of applications submitted for the execution. We split an authorization process into two levels: a coarse-grained level that manages access to a computational service; and a fine-grained level that monitors the behavior of applications executed by the computational service. Our framework guarantees that users authorized on a coarse-grained level behave as expected on the fine-grained level. Credentials obtained on the coarse-grained level reflect on fine-grained access decisions. The framework defines trust negotiations on coarse-grained level to overcome scalability problem, and preserves privacy of credentials and security policies of, both, Grid users and providers. Our authorization system was implemented to control access to the Globus Computational GRAM service. A comprehensive performance evaluation shows the practical scope of the proposed system.

Optimization of a passive vibration control scheme acting on a bladed rotor using an homogenized model

This paper deals with the optimization of a passive vibration damping system of innovative type. A bladed rotor composed of equally spaced flexible blades mounted on a flexible ring is considered. The blades are equipped with piezoelectric devices that convert vibrational energy into electrical energy, which is in turn dissipated by suitable electric shunts comprising resistive components. The optimization of these shunts, aimed at maximizing the vibration damping, is achieved by employing a simple and accurate dynamical model, derived via a homogenization procedure.     

Interactive Case-Based Planning for Forest Fire Management

This paper describes an AI system for planning the first attack on a forest fire. This planning system is based on two major techniques, case-based reasoning, and constraint reasoning, and is part of a decision support system called CHARADE. CHARADE is aimed at supporting the user in the whole process of forest fire management. The novelty of the proposed approach is mainly due to the use of a local similarity metric for case-based reasoning and the integration with a constraint solver in charge of temporal reasoning.     

Cleaning and Household Robots: A Technology Survey

This paper describes some of the main technology areas that have been actually used in the development of cleaning robots. The approach taken in this survey is to examine the characteristics of cleaning robots that have made successful laboratory demonstration or have become commercial products. We then identify the technology approach followed by the authors, and group their contributions in a few general areas. The result is a summary of used approaches to thesolution of difficult, albeit very practical, problems in the area of autonomous execution of cleaning tasks.     

Structure-based drug design to the discovery of new 2-aminothiazole CDK2 inhibitors

N-(5-Bromo-1,3-thiazol-2-yl)butanamide (compound 1) was found active (IC50=808 nM) in a high throughput screening (HTS) for CDK2 inhibitors. By exploiting crystal structures of several complexes between CDK2 and inhibitors and applying structure-based drug design (SBDD), we rapidly discovered a very potent and selective CDK2 inhibitor 4-[(5-isopropyl-1,3-thiazol-2-yl)amino] benzenesulfonamide (compound 4, IC50=20 nM). The syntheses, structure-based analog design, kinases inhibition data and X-ray crystallographic structures of CDK2/inhibitor complexes are reported.     

3-d.o.f. Wire Driven Planar Haptic Interface

A 4-wire driven 3-d.o.f. planar haptic device, called the Feriba-3, is described. The particular geometric configuration of the end-effector ensures a closed form kinematic pose solution and good manipulability. Moreover, the structural arrangement adopted makes the Feriba-3 a well-performing haptic device, whose major features are low inertia, low friction, and full dexterity in a large workspace. The manipulability analysis has been performed by introducing a complete set of manipulability indices.     

Mechanized result verification: an industrial application

We present part of an industrial project where mechanized theorem proving is used for the validation of a translator which generates safety critical software. In this project, the mechanized proof is decomposed in two parts: one is done “online”, at each run of the translator, by a custom prover which checks automatically that the result of each translation meets some verification conditions; the other is done “offline”, once for all, interactively with a general purpose prover; the offline proof shows that the verification conditions checked by the online prover are sufficient to guarantee the correctness of each translation. The provably correct verification conditions can thus be seen as specifications for the online prover. This approach is called mechanized result verification. This paper describes the project requirements and explains the motivations to formal validation by mechanized result verification, provides an overview of the formalization of the specifications for the online prover and discusses in detail some issues we have addressed in the mechanized offline proof.