The Stone Guest: How Does pH Affect Binding Properties of PD-1/PD-L1 Inhibitors?

The interaction between programmed cell death-1 (PD-1) and its ligand PD−L1 activates a coinhibitory signal that blocks T-cell activation, promoting the immune escape process in the tumor microenvironment. Development of monoclonal antibodies targeting and inhibiting PD-1/PD−L1 interaction as anticancer immunotherapies has proved successful in multiple clinical settings and for various types of cancer. Notwithstanding, limitations exist with the use of these biologics, including drug resistance and narrow therapeutic response rate in a majority of patients, that demand for the design of more efficacious small molecule-based immunotherapies. Alteration of pH in the tumor microenvironment is a key factor that is involved in promoting drug resistance, tumor survival and progression. In this study, we have investigated the effect of pH shifts on binding properties of distinct classes of PD−L1 inhibitors, including macrocyclic peptide and small molecules. Results expand structure-activity relationships of PD−L1 inhibitors, providing insights into structural features and physicochemical properties that are useful for the design of ligands that may escape a drug resistance mechanism associated to variable pH conditions of tumor microenvironment.     

SPECTRA – a Maple library for solving linear matrix inequalities in exact arithmetic

This document describes our freely distributed Maple library spectra, for Semidefinite Programming solved Exactly with Computational Tools of Real Algebra. It solves linear matrix inequalities with symbolic computation in exact arithmetic and it is targeted to small-size, possibly degenerate problems for which symbolic infeasibility or feasibility certificates are required.     

Is It Possible to Obtain Solvent-Free,Li+-Conducting Solid Electrolytes Based on Pure PVdF? Comment on “Self-Suppression of Lithium Dendrite in All-Solid-State Lithium Metal Batteries with Poly(vinylidene difluoride)-Based Solid Electrolytes”

Is It Possible to Obtain Solvent-Free, Li⁺-Conducting Solid Electrolytes Based on Pure PVdF? Comment on “Self-Suppression of Lithium Dendrite in All-Solid-State Lithium Metal Batteries with Poly(vinylidene difluoride)-Based Solid Electrolytes”     

Physical and chemical characterization of Pescabivona,a Sicilian white flesh peach cultivar [Prunus persica (L.) Batsch]

Pescabivona is an autochthonous white flesh peach cultivar population from Sicily. The composition of four Pescabivona peach landraces (Murtiddara, Bianca, Agostina, and Settembrina) at three different growing altitudes was studied. Color, color distance, weight, pulp firmness, pH, soluble solid content (SSC), titratable acidity (TA), SSC/TA ratio, organic acids, sugars, phenolics, antioxidant capacity, and lactone compounds were determined.In general for the analyzed parameters, univariate statistical analysis highlighted only a few significant differences among the landraces and the altitudes, thus demonstrating a general homogeneity of this local cultivar population. Principal component analysis, as well, did not show a clear separation among the different landraces, in particular for Bianca, Agostina, and Settembrina.The physico-chemical analysis showed high pulp firmness, high lactone content, and a balanced SSC/TA ratio. Moreover, even if the pulp firmness values were quite high for Agostina and Settembrina, sugar and acid content were typical of fresh-market quality peaches.     

Occurrence of deoxynivalenol in wheat flour,instant noodle and biscuits commercialised in Brazil

A total of 134 samples, consisting of 58 wheat flour, 40 instant noodle and 36 biscuits, were analysed for the presence of deoxynivalenol (DON). The samples were obtained from retail markets of the city of São Paulo during the period 2010–2014. DON was determined by high performance liquid chromatography with ultraviolet detection and immunoaffinity sample clean-up. Method validation followed international guidelines. The LOD and LOQ were 60 and 200 µg kg^?1, respectively, considering the three different types of samples analysed. The lowest recovery found in this study was 91.8% with RSD 4.5% for instant noodles. DON was detected in 91.4%, 97.5% and 97.2% of samples wheat flour, instant noodles and biscuits, respectively, resulting in a total of 94.8% with levels ranging from LOD to 1720.0 µg kg^?1.