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Multiple myeloma (MM) is an incurable hematologic neoplasm, whose poor prognosis is deeply affected by the propensity of tumor cells to localize in the bone marrow (BM) and induce the protumorigenic activity of normal BM cells, leading to events associated with tumor progression, including tumor angiogenesis, osteoclastogenesis, and the spread of osteolytic bone lesions. The interplay between MM cells and the BM niche does not only rely on direct cell-cell interaction, but a crucial role is also played by MM-derived extracellular vesicles (MM-EV). Here, we demonstrated that the oncogenic NOTCH receptors are part of MM-EV cargo and play a key role in EV protumorigenic ability. We used in vitro and in vivo models to investigate the role of EV-derived NOTCH2 in stimulating the protumorigenic behavior of endothelial cells and osteoclast progenitors. Importantly, MM-EV can transfer NOTCH2 between distant cells and increase NOTCH signaling in target cells. MM-EV stimulation increases endothelial cell angiogenic ability and osteoclast differentiation in a NOTCH2-dependent way. Indeed, interfering with NOTCH2 expression in MM cells may decrease the amount of NOTCH2 also in MM-EV and affect their angiogenic and osteoclastogenic potential. Finally, we demonstrated that the pharmacologic blockade of NOTCH activation by γ-secretase inhibitors may hamper the biological effect of EV derived by MM cell lines and by the BM of MM patients. These results provide the first evidence that targeting the NOTCH pathway may be a valid therapeutic strategy to hamper the protumorigenic role of EV in MM as well as other tumors.

The conservative restoration objective could be achieved through an approach to cultural heritage, optimized by diagnostics. So, it is possible to identify the causes of degradation, to monitor the effects of interventions and to guide future choices. The validity of this approach is testified by the interventions made on the Church of the Annunziata di Sessa Aurunca (CE). Inappropriate interventions and a lack of planned maintenance had caused widespread degradation. The presence of humidity was due to rising damp and condensation. After the first thermographic surveys, the restoration work began. The validation of the results had emerged from the monitoring through thermographic analysis iterated over time, which had allowed to measure the effectiveness of the interventions and to optimize the choices towards more effective actions too. The monitoring through non-destructive analysis has made it possible to develop a methodological approach that can be generalized to the historical building. Diagnostics become a system of objective measurement not only of degradation but also of the regression of degradation itself. In the reality of the restoration site, diagnostics are often overlooked with a view to reducing overall costs. This case study shows how important it is to sensitize professionals to make use of diagnostics in the approach to cultural heritage and in particular, in the case of conservative restoration, to make this preparatory phase more than desirable.

Notch signaling is a well-known key player in the communication between adjacent cells during organ development, when it controls several processes involved in cell differentiation. Notch-mediated communication may occur through the interaction of Notch receptors with ligands on adjacent cells or by a paracrine/endocrine fashion, through soluble molecules that can mediate the communication between cells at distant sites. Dysregulation of Notch pathway causes a number of disorders, including cancer. Notch hyperactivation may be caused by mutations of Notch-related genes, dysregulated upstream pathways, or microenvironment signals. Cancer cells may exploit this aberrant signaling to "educate" the surrounding microenvironment cells toward a pro-tumoral behavior. This may occur because of key cytokines secreted by tumor cells or it may involve the microenvironment through the activation of Notch signaling in stromal cells, an event mediated by a direct cell-to-cell contact and resulting in the increased secretion of several pro-tumorigenic cytokines. Up to now, review articles were mainly focused on Notch contribution in a specific tumor context or immune cell populations. Here, we provide a comprehensive overview on the outcomes of Notch-mediated pathological interactions in different tumor settings and on the molecular and cellular mediators involved in this process. We describe how Notch dysregulation in cancer may alter the cytokine network and its outcomes on tumor progression and antitumor immune response.

The aim of the experimentation is to characterize the performances of glued laminated timber components exposed to atmospheric agents, in the light of the concept of Life Cycle Cost, particularly emphasized in the Italian new legislation on public works. In fact, it could be seen that the design of the construction details and the initial characteristics of glue laminated timber components, require a particular attention to avoid errors that may undermine the possibility to perform the structural functions for which, above all, this material it is dedicated. The experimentation consisted of a series of tests aimed to identify the performance of glued laminated timber beams taken in site, after a work executed some years ago on a theatre built in Roman era, and to compare them with similarly manufactured new elements. The tests performed were thermography, ultrasound, Wood-Pecker penetrometer, mechanical characterization. The results will be used to begin setting limits and conditions for outdoor use of glue laminated timber, and assume a reliable life cycle, and consequently identify the most appropriate maintenance strategy for the LCC.

Reinforced concrete is the material with which it is built much of the architectural heritage, ordinary, but also monumental the last 100 years. Recently, there has, however, found that it is not the eternal material that you dreamed when you started to use it massively and with time degrades by various phenomena that are often attributed to the degradation that attacks the plates, but is not this the only cause which can lead to damage of the same, also the load cycles to the limits of rupture may determine, mechanically, a loss of capacity. And this, for example, the case of a building subject to an earthquake that while not causing collapse or breakage evident engages the concrete severely. The concrete thus "reduced" is still able to withstand the same loads? Is there a way to figure out when it is exceeded a threshold of attention? In this paper we want to present the results of a campaign of investigations in the laboratory with ultrasound helps to create a first answer to these questions. The technique, suitably calibrated, may be used in all those cases in which it must operate on elements that have been subject to exceptional loads to evaluate properly the areas in which it is essential to the intervention.

The assessment of the modulus of elasticity and compressive strength of masonry is a fundamental step in the seismic analysis of existing structures. In this paper, the representativeness of the values provided by flat-jack tests for tuff masonry is investigated through the analysis of a very large and homogeneous number of tests (635 double flat-jack tests). Data relate to existing buildings belonging to different historical and/or construction periods, located throughout the Campania region (Italy) in areas with different peculiarities. Results are compared with the values provided by Italian Building Code, containing ranges of the elastic modulus and compressive strength for different types of masonry. The values of flat-jack tests are then compared with laboratory tests available in the literature. Finally, comparisons with code equations are performed. It is shown that equations correlating the masonry compressive strength with the modulus of elasticity provide values larger than the mean of experimental data, whereas the equations correlating the masonry compressive strength with the strength of components provide lower values, if block and mortar strengths are varied within a probable and wide range.

This chapter aims to give an outlook on recent results concerning membranes for pure hydrogen separation, their combination with biomass processes for hydrogen production, and membrane reactors. Since hydrogen is emerging as a valuable chemical for fuel and chemical applications, membrane separation will play a critical role in its pure production. The description starts by considering the classical methane process and its extension to biogas, BioSNG and bioethanol, with a focus on the integration of membranes in processes that involve biomass feedstocks, e.g., gasification and aqueous phase reforming. A membrane catalytic reactor configuration is mainly treated to provide further advantages of higher conversions and yields owing to the hydrogen removal provided by the membrane. Some processes related to biofuel and wastewater are also described to evidence further applications. Finally, the possibilities of downsizing such processes and using modular micro-membrane reactors as an emerging technology for hydrogen production are discussed.