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The use of graphene grown by chemical vapor deposition to fabricate solution-gated field-effect transistors (SGFET) on different substrates is reported. SGFETs were fabricated using graphene transferred on poly(ethylene 2,6-naphthalenedicarboxylate) substrate in order to study the influence of using a flexible substrate for pH sensing. Furthermore, in order to understand the influence of fabrication-related residues on top of the graphene surface, a fabrication method was developed for graphene-on-SiO2 SGFETs that enables to keep a graphene surface completely clean of any residues at the end of the fabrication. We were then able to demonstrate that the electrical response of the SGFET devices to pH does not depend either on the specific substrate on which graphene is transferred or on the existence of a moderate amount of fabrication-related residues on top of the graphene surface. These considerations simplify and ease the design and fabrication of graphene pH sensors, paving the way for developing low cost, flexible, and transparent graphene sensors on plastic. We also show that the surface transfer doping mechanism does not have significant influence on the pH sensing response. This highlights that the adsorption of hydroxyl and hydronium ions on the graphene surface due to the charging of the electrical double layer capacitance is responsible for the pH sensing mechanism.

The value of in silico methods in drug development and evaluation has been demonstrated repeatedly and convincingly. While their benefits are now unanimously recognized, international standards for their evaluation, accepted by all stakeholders involved, are still to be established.In this white paper, we propose a risk-informed evaluation framework for mechanistic model credibility evaluation. To properly frame the proposed verification and validation activities, concepts such as context of use, regulatory impact and risk-based analysis are discussed. To ensure common understanding between all stakeholders, an overview is provided of relevant in silico terminology used throughout this paper.To illustrate the feasibility of the proposed approach, we have applied it to three real case examples in the context of drug development, using a credibility matrix currently being tested as a quick-start tool by Accepted ArticleThis article is protected by copyright. All rights reserved regulators. Altogether, this white paper provides a practical approach to model evaluation, applicable in both scientific and regulatory evaluation contexts.

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Manna, a very singular vegetable product derived from the spontaneous solidification of the sap of some Fraxinus species, has long been known for its mild laxative and emollient properties. In this work, a hydro-alcoholic extract of manna (HME) from Sicilian Fraxinus angustifolia Vahl was investigated using HPLC-DAD to find phenol components and using chemical and biological in vitro assays to determine its reducing, antioxidant and anti-inflammatory capacity. We identified elenolic acid, tyrosol, hydroxytyrosol, catechin, fraxetin, verbascoside, gallic acid, procyanidin-B1, and luteolin 3,7 glucoside, in order of abundance. Measurements of total antioxidant activity by Folin-Ciocalteu reaction and ferric reducing ability (FRAP), as well as of scavenger activity towards ABTS•+, DPPH•, and perferryl-myoglobin radicals, showed that the phytocomplex effectively reduced oxidants with different standard potentials. When compared with vitamin E, HME also behaved as an efficient chain-breaking antioxidant against lipoperoxyl radicals from methyl linoleate. In cellular models for oxidative stress, HME counteracted membrane lipid oxidation of human erythrocytes stimulated by tert-butyl hydroperoxide and prevented the generation of reactive oxygen species, as well as the GSH decay in IL-1β–activated intestinal normal-like cells. Moreover, in this in vitro intestinal bowel disease model, HME reduced the release of the pro-inflammatory cytokines IL-6 and IL-8. These findings may suggest that manna acts as an antioxidant and anti-inflammatory natural product in humans, beyond its well-known effects against constipation.