Rational Design of a Peptidomimetic Inhibitor of Gelsolin Amyloid Aggregation.

Gelsolin amyloidosis (AGel) is characterized by multiple systemic and ophthalmic features resulting from pathological tissue deposition of the gelsolin (GSN) protein. To date, no cure is available for the treatment of any form of AGel. More than ten single-point substitutions in the GSN gene are responsible for the occurrence of the disease and, among them, D187N/Y is the most widespread variant. These substitutions undergo an aberrant proteolytic cascade, producing aggregation-prone peptides of 5 and 8 kDa, containing the Gelsolin Amyloidogenic Core, spanning residues 182-192 (GAC182-192). Following a structure-based approach, we designed and synthesized three novel sequence-specific peptidomimetics (LB-5, LB-6, and LB-7) built on a piperidine-pyrrolidine unnatural amino acid. LB-5 and LB-6, but not LB-7, efficiently inhibit the aggregation of the GAC182-192 amyloidogenic peptides at sub-stoichiometric concentrations. These peptidomimetics resulted also effective in vivo, in a C. elegans-based assay, in counteracting the proteotoxicity of aggregated GAC182-192. These data pave the way to a novel pharmacological strategy against AGel and also validate a toolbox exploitable in other amyloidogenic diseases.

A hybrid evolutionary algorithm for wheat blending problem.

This paper presents a hybrid evolutionary algorithm to deal with the wheat blending problem. The unique constraints of this problem make many existing algorithms fail: either they do not generate acceptable results or they are not able to complete optimization within the required time. The proposed algorithm starts with a filtering process that follows predefined rules to reduce the search space. Then the linear-relaxed version of the problem is solved using a standard linear programming algorithm. The result is used in conjunction with a solution generated by a heuristic method to generate an initial solution. After that, a hybrid of an evolutionary algorithm, a heuristic method, and a linear programming solver is used to improve the quality of the solution. A local search based posttuning method is also incorporated into the algorithm. The proposed algorithm has been tested on artificial test cases and also real data from past years. Results show that the algorithm is able to find quality results in all cases and outperforms the existing method in terms of both quality and speed.

Computer-based simulator for catheter insertion training.

Minimally invasive surgery procedures are getting common in surgical practice; however the new interventional procedure requires different skills compared to the conventional surgical techniques. The need for training process is very important in order to successfully and safely execute a surgical procedure. Computer-based simulators, with appropriate tactile feedback device, can be an efficient method for facilitating the education and training process. In addition, virtual reality surgical simulators can reduce costs of education and provide realism with regard to tissues behaviour and real-time interaction. This work take into account the results of the HERMES Project (HEmatology Research virtual MEdical System), conceived and managed by Consorzio CETMA-Research Centre; the aim of this project is to build an integrate system in order to simulate a coronary angioplasty intervention.