Discriminating between competing models for the allosteric regulation of oncogenic phosphatase SHP2 by characterizing its active state

The Src-homology 2 domain containing phosphatase 2 (SHP2) plays a critical role in crucial signaling pathways and is involved in oncogenesis and in developmental disorders. Its structure includes two SH2 domains (N-SH2 and C-SH2), and a protein tyrosine phosphatase (PTP) domain. Under basal conditions, SHP2 is auto-inhibited, with the N-SH2 domain blocking the PTP active site. Activation involves a rearrangement of the domains that makes the catalytic site accessible, coupled to the association between the SH2 domains and cognate proteins containing phosphotyrosines. Several aspects of this transition are debated and competing mechanistic models have been proposed. A crystallographic structure of SHP2 in an active state has been reported (PDB code 6crf), but several lines of evidence suggests that it is not fully representative of the conformations populated in solution. To clarify the structural rearrangements involved in SHP2 activation, enhanced sampling simulations of the autoinhibited and active states have been performed, for wild type SHP2 and its pathogenic E76K variant. Our results demonstrate that the crystallographic conformation of the active state is unstable in solution, and multiple interdomain arrangements are populated, thus allowing association to bisphosphorylated sequences. Contrary to a recent proposal, activation is coupled to the conformational changes of the N-SH2 binding site, which is significantly more accessible in the active sate, rather than to the structure of the central β-sheet of the domain. In this coupling, a previously undescribed role for the N-SH2 BG loop emerged

Total- and semi-bare noble metal nanoparticles@silica core@shell catalysts for hydrogen generation by formic acid decomposition

Catalysts are involved in a number of established and emerging chemical processes as well as in environmental remediation and energy conversion. Nanoparticles (NPs) can offer several advantages over some conventional catalysts, such as higher efficiency and selectivity. Nowadays, versatile and scalable nanocatalysts that combine activity and stability are still lacking. Here, we report a comprehensive investigation on the production and characterization of hybrid nano-architectures bringing a partial or total bare surface together with their catalytic efficiency evaluation on, as a proof-of-concept, the formic acid decomposition reaction. In this regard, formic acid (FA) is a convenient and safe hydrogen carrier with appealing features for mobile applications, fuel cells technologies, petrochemical processes and energetic applications. Thus, the design of robust catalysts for FA dehydrogenation is strongly demanded. Due to this, we produced and evaluated nano-architectures with various equilibrium between the size-increase of the active part and the barer catalytic surface. Overall, this work paves the way for the development of new approaches for green energy storage and safe delivery

Towards a Semantic Document Management System for Public Administration

This work has two objectives: to summarize the experiences carried out over the past four years by the National Interuniversity Consortium for Informatics (CINI) in the Datalake project funded by the CRUI in collaboration with the Directorate General of Automated Information Systems (DGSIA) of the Ministry of Justice, in synergy with other related projects of the Ministry; and to demonstrate how the experiences, Proof of Concepts, and functional specifications produced can serve as a repository of functionalities for a “semantic document management system for PA,” which aims to evolve the information systems of PAs into platforms where unstructured data can be exploited and integrated with structured data to enhance and add value to the digital services provided by the PA, and where governance processes can be conducted using all knowledge expressed in documents and other forms of unstructured data. The judicial organization, proceedings, processes, user needs, functional structure of the Datalake, and implementation architecture are described, aiming towards a design and production pathway directed at all PAs

Field emission from single and few-layer graphene flakes

We report the observation and characterization of field emission current from individual single- and few-layer graphene flakes laid on a flat SiO2/Si substrate. Measurements were performed in a scanning electron microscope chamber equipped with nanoprobes, used as electrodes to realize local measurements of the field emission current. We achieved field emission currents up to 1 {\mu}A from the flat part of graphene flakes at applied fields of few hundred V/{\mu}m. We found that emission process is stable over a period of several hours and that it is well described by a Fowler-Nordheim model for currents over 5 orders of magnitude

Electromechanically active pair dynamics in a Gd-doped ceria single crystal

Oxygen-defective ceria, e.g. Gd-doped ceria, shows giant electromechanical properties related to a complex local rearrangement of its lattice. Although they are not entirely identified, the electroactive mechanisms arise from cation and oxygen vacancy (V-O) pairs (i.e. Ce-V-O), and the local structural elastic distortion in their surroundings. Here, we study the geometry and behaviour of Ce-V-O pairs in a grain boundary-free bulk Ce0.9Gd0.1O1.95 single crystal under an AC electric field of ca. 11 kV cm(-1). The analysis was carried out through X-ray absorption spectroscopy (XAS) techniques at the Ce L-III edge. Using Density Functional Theory (DFT) calculations, we investigated the effects of the strain on density of states and orbitals at the valence band edge. Our research indicates that electrostriction increases at low temperatures. The electromechanical strain has a structural nature and can rise by one order of magnitude, i.e., from 5 x 10(-4) at room temperature to 5 x 10(-3) at -193 degrees C, due to an increase in the population of the electrically active pairs. At a constant V-O concentration, the material can thus configure heterogeneous pairs and elastic nanodomains that are either mechanically responsive or not