The role of the masonry quality evaluation in historic constructions: the case of St. Paul hospital of Savona, Italy

The lack of monolithic behaviour can be the worst structural defect of a masonry wall and this can happen in case of poor quality, for instance when the wall is made of multiple leaves, well ordered but not mutually connected. This causes the wall to become more vulnerable with the separation of the leaves especially when external forces act in the horizontal direction. Serious mistakes can be made in the structural evaluation of a historic stone masonry if the definition of the masonry typology, following the present Italian seismic code, is incorrect. In several cases a masonry texture can appear irregular from the facade with small irregular stones of different dimensions while the cross section shows a well-interlocked masonry with long stones used as connection among the leaves. The latter example is the case of the XIX cent. ex-hospital of Savona, a three storey masonry building. Here a comparison among the quality surveys (direct inspection of the whole cross section), non-destructive tests (pulse sonic velocity and flat jack tests) and the destructive tests (diagonal tests) results was carried out showing a reliable mechanical behaviour despite the appearance of the masonry texture. The results of the experimental investigation will be presented and discussed in the paper, and an attempt will be made to suggest improvement to the masonry typology table of the Italian Code

Circulating endocannabinoids are differentially modulated during the oral glucose tolerance test

The endocannabinoid system (ECS) is involved in the regulation of food intake and energy expenditure. Increased level of EC lipid mediators anandamide (AEA) and 2-arachydonoylglycerol (2AG) and/or a higher expression of cannabinoid receptor type 1 in central and peripheral districts are supposed to contribute to the development and maintenance of obesity and related dismetabolism. To understand the ECS response to insulin signal and to anthropometric and biochemical parameters, we evaluated the effect of an OGTT on circulating ECs in five fasted obese females (age: 41.4G3.6 years, BMI: 32.5G4.2 kg/m2, waist circumference: 103.4G11.1 cm). Blood samples were collected before and after 30, 60, 90 and 120 min from a 75 g glucose ingestion. Plasma AEA, related Nacylethanolamines palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), 2AG and 1AG were measured by LC\u2013MS/MS. A whole body and specific region composition analysis was performed by dual-energy X-ray absorptiometry. Basal insulin and glucose levels were 9.4G1.1 mU/ml and 91.0G 5.4 mg/dl, and the calculated area under curve (AUC) were 9.777G2.601 and 15 375G4.044 respectively. AEA, PEA, OEA, 2AG and 1AG basal levels were 1.280G0.498, 15.48G3.70, 4.244G1.450, 1.498G0.465 and 0.588G 0.192 pmol/ml respectively. AEA, PEA and OEA significantly decreased along the OGTT (PZ0.004, PZ0.001 and PZ0.003 respectively). At 60 min their level (D(t0Kt60)/t0%) reduced to 0.639G0.340 (51.4%), 9.16G3.69 (41.2%) and 2.276G0.906 pmol/ml (44.9%). Conversely, 2AG and 1AG levels did not significantly change. AEA, PEA and OEA reduction (D(t0Kt60)/t0%) negatively correlated with glucose AUC (rZK0.895, PZ0.040; rZK0.929, PZ0.022; rZK0.948, PZ0.014 respectively) and positively with whole body (rZ0.882, PZ0.048; rZ0.910, PZ0.032; rZ0.944, PZ0.016 respectively) and gynoid lean mass (rZ0.957, PZ0.010; rZ0.967, PZ0.007; rZ0.951, PZ0.013 respectively). No significant correlations were observed for BMI, waist circumference, basal glucose and insulin, insulin AUC and blood lipids. Our preliminary data indicated that N-acylethanolamine levels are suppressed during the OGTT, and that the extent of the suppression is promoted by lean mass and affected by increasing glucose AUC

CRISPR mediated transactivation in the human disease vector Aedes aegypti.

As a major insect vector of multiple arboviruses, Aedes aegypti poses a significant global health and economic burden. A number of genetic engineering tools have been exploited to understand its biology with the goal of reducing its impact. For example, current tools have focused on knocking-down RNA transcripts, inducing loss-of-function mutations, or expressing exogenous DNA. However, methods for transactivating endogenous genes have not been developed. To fill this void, here we developed a CRISPR activation (CRISPRa) system in Ae. aegypti to transactivate target gene expression. Gene expression is activated through pairing a catalytically-inactive ('dead') Cas9 (dCas9) with a highly-active tripartite activator, VP64-p65-Rta (VPR) and synthetic guide RNA (sgRNA) complementary to a user defined target-gene promoter region. As a proof of concept, we demonstrate that engineered Ae. aegypti mosquitoes harboring a binary CRISPRa system can be used to effectively overexpress two developmental genes, even-skipped (eve) and hedgehog (hh), resulting in observable morphological phenotypes. We also used this system to overexpress the positive transcriptional regulator of the Toll immune pathway known as AaRel1, which resulted in a significant suppression of dengue virus serotype 2 (DENV2) titers in the mosquito. This system provides a versatile tool for research pathways not previously possible in Ae. aegypti, such as programmed overexpression of endogenous genes, and may aid in gene characterization studies and the development of innovative vector control tools

Engineered Antiviral Sensor Targets Infected Mosquitoes

Escalating vector disease burdens pose significant global health risks, as such innovative tools for targeting mosquitoes are critical. CRISPR-Cas technologies have played a crucial role in developing powerful tools for genome manipulation in various eukaryotic organisms. Although considerable efforts have focused on utilizing class II type II CRISPR-Cas9 systems for DNA targeting, these modalities are unable to target RNA molecules, limiting their utility against RNA viruses. Recently, the Cas13 family has emerged as an efficient tool for RNA targeting; however, the application of this technique in mosquitoes, particularly Aedes aegypti, has yet to be fully realized. In this study, we engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR-Cas13 and its potent collateral activity. REAPER remains concealed within the mosquito until an infectious blood meal is uptaken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13-mediated RNA targeting significantly reduces viral replication and viral prevalence of infection, and its promiscuous collateral activity can even kill infected mosquitoes within a few days. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission

Information asymmetries in banking and financial contracts: possible solutions from legal design.

In banking the strength of the Credit Institution is manifested in relation to the customer, who therefore assumes the role of a weak contractor, deserving of particular protection. Awareness of the characteristics of the products offered by banks, the comparison between the different services offered on the market and the opportunity to make an informed choice are all consequences linked to the information that is made available. Such information is above all unclear, so much so as to make it difficult to effectively evaluate the convenience of the operations and services offered. Specific rules are envisaged that intervene in the various phases in which the bank-customer relationship is divided. But it almost always happens that the documentation prepared by intermediaries is difficult to read and understand due to their technicality or to the use of a language that is not always easily understood. Everything described falls within the general discipline of banking and financial contracts which is today extremely complex, requires a particular study analysis of the various sectors governed by practices and regulatory interventions that are not always clear to customers and which should, instead, be made accessible through new solutions proposed by the world of legal design