Polytechnic University of Turin

About: Polytechnic University of Turin is a education organization based out in Turin, Piemonte, Italy. It is known for research contribution in the topics: Finite element method & Nonlinear system. The organization has 11553 authors who have published 41395 publications receiving 789320 citations. The organization is also known as: POLITO & Politecnico di Torino.

Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design.

Abstract: The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mixed-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar severe acute respiratory syndrome (SARS) Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins showed major differences in both shape and size, indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site's conformational changes during the simulation time indicated its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicated that the virus' mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.

Subdominant Dense Clusters Allow for Simple Learning and High Computational Performance in Neural Networks with Discrete Synapses

Abstract: We show that discrete synaptic weights can be efficiently used for learning in large scale neural systems, and lead to unanticipated computational performance. We focus on the representative case of learning random patterns with binary synapses in single layer networks. The standard statistical analysis shows that this problem is exponentially dominated by isolated solutions that are extremely hard to find algorithmically. Here, we introduce a novel method that allows us to find analytical evidence for the existence of subdominant and extremely dense regions of solutions. Numerical experiments confirm these findings. We also show that the dense regions are surprisingly accessible by simple learning protocols, and that these synaptic configurations are robust to perturbations and generalize better than typical solutions. These outcomes extend to synapses with multiple states and to deeper neural architectures. The large deviation measure also suggests how to design novel algorithmic schemes for optimization based on local entropy maximization.

Technical note - Experimental Studies on the mechanical behaviour of two thermal cracked marbles

Abstract: 1. IntroductionThe specific aim of this paper is to find an experimental methodology which couldmeasure crack density in rock and its influence on the behaviour of the rockmaterial. The results of both experimental and numerical simulations showed thatrock behaviour is mainly ruled by crack density within a specific rock volume. Thebehaviour of a rock with di¤erent crack densities has been studied by severalauthors, from the theoretical point of view and through experiments.Experimental works (Sage, 1988; Rotonda, 1991; Franzini, 1995; Homard-Etienne and Houpert, 1989) have confirmed that a large, damaged area in a rockmaterial induced by heating determines variations of rock properties that areclosely connected to the degree of fracturing of the material. It has been shownthat the overall moduli of elasticity and tensile strength are influenced by thepresence of cracks (Yin and Ehrlacher, 1996; Wong et al., 1996; Laws andBrockenbrough, 1982; Bertagnini at al., 1993).2. Experimental StudiesSpecimens of two di¤erent types of marbles have been heated at di¤erent temper-atures to induce micro-cracking.The rock materials used in the testing campaign are two Italian ornamentalstones: