The Personality Trait of Environmental Sensitivity Predicts Children's Positive Response to School-Based Antibullying Intervention

Background: Meta-analyses on the effectiveness of anti-bullying interventions show that average effects tend to be significant but small. Informed by the Vantage Sensitivity framework (Pluess and Belsky, 2013) the current study aims at testing whether individual differences in Environmental Sensitivity predict treatment response to an anti-bullying intervention. Method: Large randomized controlled trial with 2,042 pupils (grade 4 and 6) randomly assigned to a treatment or control condition. Results: Significant Intervention effects on victimization and internalizing symptoms (but not bullying or externalizing symptoms) were moderated by both Environmental Sensitivity and gender, with boys scoring high on sensitivity benefitting significantly more than less sensitive boys from the effects of the intervention regarding reduced victimization and internalizing symptoms. Conclusions: Findings are consistent with the notion of Vantage Sensitivity, suggesting that some individuals are disproportionately likely to respond to treatment while others are more resistant as a function of individual differences in environmental sensitivity

Design of a hydraulic servo-actuation fed by a regenerative braking system

Many conventional truck and working machines are equipped with additional hydraulic tooling or manipulation systems which are usually fed through a mechanical connection with the internal combustion engine, involving a poor efficiency. In particular, this is a common situation for industrial vehicles whose mission profiles involves a relevant consumption of energy by the on board hydraulic systems, respect to the one really needed for only traction purpose. In this work it is proposed an innovative solution based on the adoption of a system aimed to recover braking energy in order to feed an efficient on board hydraulic actuation system. The proposed system is then adopted to a real application, an Isuzu truck equipped with a hydraulic tooling for garbage collection. A prototype of the system has been designed, assembled and tested showing a relevant improvement of system efficiency and the feasibility of the proposed approach. In the paper the proposed solution is presented, showing the simulation models and preliminary validation results including experimental devices assembled to perform the tests

Native mass spectrometry of human carbonic anhydrase I and its inhibitor complexes

Abstract: Native mass spectrometry is a potent technique to study and characterize biomacromolecules in their native state. Here, we have applied this method to explore the solution chemistry of human carbonic anhydrase I (hCA I) and its interactions with four different inhibitors, namely three sulfonamide inhibitors (AAZ, MZA, SLC-0111) and the dithiocarbamate derivative of morpholine (DTC). Through high-resolution ESI-Q-TOF measurements, the native state of hCA I and the binding of the above inhibitors were characterized in the molecular detail. Native mass spectrometry was also exploited to assess the direct competition in solution among the various inhibitors in relation to their affinity constants. Additional studies were conducted on the interaction of hCA I with the metallodrug auranofin, under various solution and instrumental conditions. Auranofin is a selective reagent for solvent-accessible free cysteine residues, and its reactivity was analyzed also in the presence of CA inhibitors. Overall, our investigation reveals that native mass spectrometry represents an excellent tool to characterize the solution behavior of carbonic anhydrase. Graphic abstract: [Figure not available: see fulltext.]

7-Acylamino-3H-1,2-benzoxathiepine 2,2-dioxides as new isoform-selective carbonic anhydrase IX and XII inhibitors

A series of 3H-1,2-benzoxathiepine 2,2-dioxides incorporating 7-acylamino moieties were obtained by an original procedure starting from 5-nitrosalicylaldehyde, which was treated with propenylsulfonyl chloride followed by Wittig reaction of the bis-olefin intermediate. The new derivatives, belonging to the homosulfocoumarin chemotype, were assayed as inhibitors of the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Four pharmacologically relevant human (h) isoforms were investigated, the cytosolic hCA I and II and the transmembrane, tumour-associated hCA IX and XII. No relevant inhibition of hCA I and II was observed, whereas some of the new derivatives were effective, low nanomolar hCA IX/XII inhibitors, making them of interest for investigations in situations in which the activity of these isoforms is overexpressed, such as hypoxic tumours, arthritis or cerebral ischaemia

Aryl derivatives of 3H-1,2-benzoxathiepine 2,2-dioxide as carbonic anhydrase inhibitors

A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance