Limitations and challenges in protein stability prediction upon genome variations: towards future applications in precision medicine

Protein stability predictions are becoming essential in medicine to develop novel immunotherapeutic agents and for drug discovery. Despite the large number of computational approaches for predicting the protein stability upon mutation, there are still critical unsolved problems: 1) the limited number of thermodynamic measurements for proteins provided by current databases; 2) the large intrinsic variability of \u394\u394G values due to different experimental conditions; 3) biases in the development of predictive methods caused by ignoring the anti-symmetry of \u394\u394G values between mutant and native protein forms; 4) over-optimistic prediction performance, due to sequence similarity between proteins used in training and test datasets. Here, we review these issues, highlighting new challenges required to improve current tools and to achieve more reliable predictions. In addition, we provide a perspective of how these methods will be beneficial for designing novel precision medicine approaches for several genetic disorders caused by mutations, such as cancer and neurodegenerative diseases

Explicit meshfree solution for large deformation dynamic problems in saturated porous media

In this paper a new methodology to simulate saturated soils subjected to dynamic loadings under large deformation regime (locally up to 40% in equivalent plastic strain) is presented. The coupling between solid and fluid phases is solved through the complete formulation of the Biot’s equations. The additional novelty lies in the employment of an explicit time integration scheme of the u−w (solid displacement–relative fluid displacement) formulation which enables us to take advantage of such explicit schemes. Shape functions based on the principle of maximum entropy implemented in the framework of Optimal Transportation Meshfree schemes are utilized to solve both elastic and plastic problems

u–w formulation for dynamic problems in large deformation regime solved through an implicit meshfree scheme

Solving dynamic problems for fluid saturated porous media at large deformation regime is an interesting but complex issue. An implicit time integration scheme is herein developed within the framework of the u–w (solid displacement–relative fluid displacement) formulation for the Biot’s equations. In particular, liquid water saturated porous media is considered and the linearization of the linear momentum equations taking into account all the inertia terms for both solid and fluid phases is for the first time presented. The spatial discretization is carried out through a meshfree method, in which the shape functions are based on the principle of local maximum entropy LME. The current methodology is firstly validated with the dynamic consolidation of a soil column and the plastic shear band formulation of a square domain loaded by a rigid footing. The feasibility of this new numerical approach for solving large deformation dynamic problems is finally demonstrated through the application to an embankment problem subjected to an earthquake

Remineralization strategies in oral hygiene: A position paper of italian society of oral hygiene sciences-S.I.S.I.O. working group

Background/Objective: The clinical conditions that lead to an alteration of the enamel structure are numerous. The diet high in sugars and acidifying substances, psychological stress that triggers parafunctional behaviors, the reduced intake of fiber-rich foods or alkalizing substances, together with other factors, contribute to demineralization of the tooth enamel. Dental mineralizing products on the current market are distinguished according to the dosage form, the active ingredient, the release technology, clinical indications and patient choice. Currently, it is necessary to propose to oral health professionals a guide to orient themselves in this chaotic choice, in order to prefer the most effective product for their own clinical target. Methods: Italian Society of Oral Hygiene Sciences-S.I.S.I.O. is one of the leading scientific Italian societies representing those dental hygienists working with high-quality standards and in agreement with scientific evidence: in the last year, the SISIO working group has carried out a study focused on remineralizing agents in dentistry, in order to give an authoritative point of view to indicate a guideline in the decision process of the choice of a remineralizing agent. We will report the results pointed out from the last consensus meeting in 2017. Results: We have reported the good the bad and the ugly have been discussed in a critical discussion of such topic. Conclusion: The SISIO experience has been reported in this position paper with the aim to serve as a useful aid in the daily choice of the clinical steps to perform, when dental professionals need to treat demineralized teeth