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The conditions of road structures, play a considerable role in relation to the duration of its operational suitability. In this way maintenance money is smart money because maintaining roads is not optional. It protects not only the asset investment, but keeps travelling safe for road users. The use of technology to assess the fatigue properties and the integrity of the load-bearing capacity is of vital importance. The evaluation of these critical parameters is used as a basis for the development of a method to determine the remaining useful life, to estimate the scope and intervals of maintenance by specific management software, and finally to improve quality and the resulting long operational suitability. The subsequent lower number of necessary road works will generate financial savings and in general optimization of available resources. These objectives will be met by employing automated measuring systems to replace manual methods. An automated measurement system is less resource and time consuming and provides a greater quantity of useful data while considerably reducing traffic interference. The ANAS Quality Evaluation Management System (QEMS) is an innovative tool that enables the collection, the analysis and the evaluation of all the information related to road pavement, both for new construction projects and maintenance of existing roads. Beside this, the system issues on-time quality reports which include information about the progress and the quality of the activities, and information about the performances of the Key Suppliers (KS). Based on this, the QEMS aims to allow monitoring the specific quality performance of each and all activities carried by the KS. In addition, it can be used by each KS, who is allowed accessing solely its own results. This interactive tool is proposed as a support to enhance the quality of road construction by providing a synthetic and on-time analysis of performances to put in place fast and optimized solutions the first time. In the QEMS, each project is divided into several audit areas each characterized by a unique pavement structure. Then, in each Audit Area, the activities of each KS (e.g., laying, compaction), are audited acquiring selected information (laboratory test data, on site audit, management quality audit), defined as parameters, which represent the evaluation criteria to assess quality and whose results, converted in normalized scores, represent the Quality Indicators (QIs). Within the same audit area all the activities are organized into a hierarchical structure, called Activity Tree, where their quality depends on the quality and the weight factors of activities and parameters at lower levels. This paper describes the concepts behind the QEMS, which is the result of an ANAS significant Project. It includes the system configuration adapted to road work construction. However, the QEMS shows flexibility that enables its application to other civil engineering construction activities such as building, bridges and ports in general. Implementing the most cutting-edge technologies allows not just the construction of world-class roads, but also the optimization of the maintaining costs.

Tumor acidity is now considered an important determinant of drug-resistance and tumor progression, and anti-acidic approaches, such as Proton Pump inhibitors (PPIs), have demonstrated promising antitumor and chemo-sensitizing efficacy. The main purpose of the present study was to evaluate the possible PPI-induced sensitization of human melanoma cells to Paclitaxel (PTX). Our results show that PTX and the PPI Lansoprazole (LAN) combination was extremely efficient against metastatic melanoma cells, as compared to the single treatments, both in vitro and in vivo. We also showed that acidity plays an important role on the anti-tumor activity of these drugs, being detrimental for PTX activity, while crucial for the synergistic effect of PTX following pretreatment with LAN, due to its nature of pro-drug needing protonation for a full activation. We obtained straightforward results in a human melanoma xenograft model combining well tolerated LAN doses with suboptimal and poorly toxic doses of PTX. With this study we provide a clear evidence that the PPI LAN may be included in new combined therapy of human melanoma together with low doses of PTX.

Accidents involving roadsides are typically extremely “unforgiving”. Even though the roadside design can affect only marginally the actual number of accidents occurring on a road, the severity of crashes can be considerably reduced if roadsides are designed to be more “forgiving”.Within the IRDES project a practical and uniform guideline that allows the road designer to improve the forgivingness of the roadside and a practical tool for assessing the effectiveness of applying a given roadside treatment have been produced for the following set of roadside features: barrier terminals; shoulder rumble strips; forgiving support structures for road equipment; shoulder width.

Here we report a novel strategy for the induction of CD8(+) T cell adaptive immune response against viral and tumor antigens. This approach relies on high levels of incorporation in HIV-1 VLPs of a mutant of HIV-1 Nef (Nef(mut)) which can act as anchoring element for foreign proteins. By in vitro assay, we found that VLP-associated Nef(mut) is efficiently cross-presented by antigen presenting cells. Inoculation in mice of VLPs incorporating the HPV-16 E7 protein fused to Nef(mut) led to an anti-E7 CD8(+) T cell response much stronger than that elicited by E7 recombinant protein inoculated with incomplete Freund's adjuvant and correlating with well-detectable anti-E7 CTL activity. Most relevantly, mice immunized with Nef(mut)-E7 VLPs developed a protective immune response against tumors induced by E7 expressing tumor cells. These results make Nef(mut) VLPs a promising candidate for new vaccine strategies focused on the induction of CD8(+) T cell immunity.

The infection of cynomolgus monkeys with an attenuated simian immunodeficiency virus (SIV) (C8) carrying a deletion in the nef gene results in a persistent infection associated with an extremely low viral burden in peripheral blood mononuclear cells. The aim of this study was to determine (1) the breadth of the protection after repeated challenges of monkeys with SIV homologous strains of different pathogenicity, (2) the genotypic stability of the live virus vaccine, (3) whether the protection might depend on cellular resistance to superinfection, and (4) whether immunogenic stimuli such as recall antigens could reactivate the replication of the C8 virus. To address these goals, the monkeys were challenged at 40 weeks after C8 infection with 50 MID50 of cloned SIVmac251, BK28 grown on macaque cells. They were protected as indicated by several criteria, including virus isolation, anamnestic serological responses, and viral diagnostic PCR. At 92 weeks after the first challenge, unfractionated peripheral blood mononuclear cells from protected monkeys were susceptible to the in vitro infection with SIVmac32H, spl. At 143 weeks after C8 infection, the four protected monkeys were rechallenged with 50 MID50 of the pathogenic SIVmac32H, spl grown on macaque cells. Once again, they were protected. The C8 virus remained genotypically stable, and depletion of CD4(+) cells was not observed during approximately 3 years of follow-up. In contrast, it was found that the infection with SIVmac32H, spl induced CD4(+) cell depletion in three of three control monkeys. Of importance, stimulation with tetanus toxoid, although capable of inducing specific humoral and T cell proliferative responses, failed to induce a detectable reactivation of C8 virus.