Edoardo Benvenuto Prize. Collection of papers

The promotion of studies and research on the science and art of building in their historical development constitutes the objective that the Edoardo Benvenuto Association has set itself, since its establishment, in order to honor the memory of Edoardo Benvenuto (1940-1998). The Association in recent years has achieved interesting results by developing various activities such as: organization of national and international meetings, conferences, study days; collaborations with national and foreign research institutions; promotion of the editorial series “Between Mechanics and Architecture"; activation of the portal Bibliotheca Mechanica Architectonica, first “open source” digitized library dedicated to historical research on mechanical and architectural texts. But perhaps the most qualifying initiative was the institution of the Edoardo Benvenuto Prize, arrived in 2019 in its twelfth edition, reserved for young researchers in the field of historical studies on science and the art of building. The awarding of the Prize takes place after an in-depth examination of the texts received by the Association by an international commission of experts. The purpose of this book is to collect and present the most recent studies and publications produced by the winners of the various editions of the Edoardo Benvenuto Prize

GM1 as adjuvant of innovative therapies for cystic fibrosis disease

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM1, it becomes a component of the PM, reducing the destabilizing effect of the potentiator VX-770 on rescued CFTR protein expression/function and improving its stabilization. This evidence could represent a starting point for developing innovative therapeutic strategies based on the co-administration of GM1, correctors and potentiators, with the aim of improving F508del CFTR function

The free license codes as decision support system (DSS) for the emergency planning to simulate radioactive releases in case of accidents in the new generation energy plants

The radiological risk is related to a wide range of activities, beginning with the medical and military ones and including those connected to the industrial and research activities such as nuclear fusion. A valid tool to predict the consequences of the accidents and reduce the risk is represented by computing systems that allow modeling the evolution of a possible release of radioactive materials over time and space. In addition to proprietary codes there are free license codes, like Hot-Spot, that allow providing a set of tools to simulate diffusion in case of accidents involving radioactive materials and analyze the safety and security of the facilities in which the radioactive material is manipulated. The case studies scenario’s consists in two simulations accidents scenario the first to biomass plant and the second at nuclear fission plant. The simulation of the radioactive contamination have been conducted with the code HOT SPOT, a free license code. The results of the simulation and data discussion will be presented in this work by the authors

Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2.

Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF). A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16) or anoctamin (ANO). TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT). The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Edoardo Benvenuto: un uomo del Rinascimento nel XX secolo. Dialoghi intorno alla cultura umanistica e scientifica

Il volume raccoglie gli Atti del convegno dedica-to a Edoardo Benvenuto in occasione del ventesimo anniversario dalla sua dipartita. Il 29 novembre 2018, nell\u2019aula magna a lui dedicata del Dipartimento Architettura e Design della Scuola Politecnica dell\u2019Ateneo genovese, si \ue8 tenuta infatti una giornata di studi sulla figura di Edoardo Ben-venuto (1940-1998), promossa dall\u2019Associazione Edoardo Benvenuto e dal Dipartimento Architettura e Design dell\u2019Universit\ue0 di Genova, in collaborazione con la Fondazione dell\u2019Ordine degli Architetti Pianificatori Paesaggisti e Conservatori della Provincia di Genova, l\u2019Ordine degli Architetti Pianifica-tori Paesaggisti e Conservatori di Genova e l\u2019Associazione Amici del Liceo Colombo di Genova. L\u2019incontro si \ue8 posto un duplice obiettivo, tra memoria e prospettiva: da un lato ricordare Edoardo at-traverso le parole di amici e colleghi, dall\u2019altro far conoscere la sua figura poliedrica alle nuove gene-razioni di studenti e di studiosi. Il titolo dell\u2019incontro ha inteso presentare, per quanto possibile, a tutto tondo, l\u2019uomo, il docente, il sognatore, lo studioso: Edoardo Benvenuto: un uomo del Rinascimento nel XX secolo. Dialoghi intorno alla cultura umanistica e scientifica. Al termine dell\u2019incontro \ue8 sembrato naturale e utile offrire l\u2019opportunit\ue0 di condividere la ricchezza di spunti emersa dall\u2019iniziativa con altre persone che, su piani diversi, avrebbero potuto apprezzarla: sia tutti coloro che, avendo conosciuto Edoardo, si erano trovati impossibilitati ad essere presenti quel giorno pur desiderando parteciparvi, sia coloro che, non avendo conosciuto Edoardo, avrebbero potuto scoprirne per la prima volta la profondit\ue0 umana e culturale. Il volume intende onorare l\u2019impegno. Esso \ue8 costituito dai contributi presentati il 29 novembre 2018, che risultano suddivisi in due parti, come durante la giornata di studi. Si tratta di tredici \u201cdialoghi\u201d: in-torno a filosofia, teologia, arte, musica e letteratura, temi tutti \u201cvissuti\u201d da Edoardo nella sua esperienza di vita e di studio, strettamente correlati a quelli intorno ad architettura, storia della scienza e scienza delle costruzioni. Un autentico bailamme: ma nel senso proprio del termine in lingua turca, bayram, dal quale deriva, che propriamente significa festa, piuttosto che nel significato col quale spesso viene usato: confusione. Una festa del conoscere, condividere, pensare, elaborare, trasmettere, fino a scorgerne la pi\uf9 intima appartenenza alle sfere dello spirituale e del politico, termini anch\u2019essi interpretati nel senso autentico, piuttosto che antico: come spesso lo stesso Edoardo richiamava

Edoardo Benvenuto: un uomo del Rinascimento nel XX secolo. Dialoghi intorno alla cultura umanistica e scientifica.

Il volume raccoglie gli Atti del convegno dedicato a Edoardo Benvenuto in occasione del ventesimo anniversario dalla sua dipartita. Il 29 novembre 2018, nell’aula magna a lui dedicata del Dipartimento Architettura e Design della Scuola Politecnica dell’Ateneo genovese, si è tenuta infatti una giornata di studi sulla figura di Edoardo Benvenuto (1940-1998), promossa dall’Associazione Edoardo Benvenuto e dal Dipartimento Architettura e Design dell’Università di Genova, in collaborazione con la Fondazione dell’Ordine degli Architetti Pianificatori Paesaggisti e Conservatori della Provincia di Genova, l’Ordine degli Architetti Pianificatori Paesaggisti e Conservatori di Genova e l’Associazione Amici del Liceo Colombo di Genova. L’incontro si è posto un duplice obiettivo, tra memoria e prospettiva: da un lato ricordare Edoardo attraverso le parole di amici e colleghi, dall’altro far conoscere la sua figura poliedrica alle nuove generazioni di studenti e di studiosi. Il titolo dell’incontro ha inteso presentare, per quanto possibile, a tutto tondo, l’uomo, il docente, il sognatore, lo studioso: Edoardo Benvenuto: un uomo del Rinascimento nel XX secolo. Dialoghi intorno alla cultura umanistica e scientifica. Al termine dell’incontro è sembrato naturale e utile offrire l’opportunità di condividere la ricchezza di spunti emersa dall’iniziativa con altre persone che, su piani diversi, avrebbero potuto apprezzarla: sia tutti coloro che, avendo conosciuto Edoardo, si erano trovati impossibilitati ad essere presenti quel giorno pur desiderando parteciparvi, sia coloro che, non avendo conosciuto Edoardo, avrebbero potuto scoprirne per la prima volta la profondità umana e culturale. Il volume intende onorare l’impegno. Esso è costituito dai contributi presentati il 29 novembre 2018, che risultano suddivisi in due parti, come durante la giornata di studi. Si tratta di tredici “dialoghi”: intorno a filosofia, teologia, arte, musica e letteratura, temi tutti “vissuti” da Edoardo nella sua esperienza di vita e di studio, strettamente correlati a quelli intorno ad architettura, storia della scienza e scienza delle costruzioni. Un autentico bailamme: ma nel senso proprio del termine in lingua turca, bayram, dal quale deriva, che propriamente significa festa, piuttosto che nel significato col quale spesso viene usato: confusione. Una festa del conoscere, condividere, pensare, elaborare, trasmettere, fino a scorgerne la più intima appartenenza alle sfere dello spirituale e del politico, termini anch’essi interpretati nel senso autentico, piuttosto che antico: come spesso lo stesso Edoardo richiamava

Improving Operational Procedures to Access Industrial Facilities and Urban Areas during Pandemics

Management of population crowds and their access to critical infrastructures is crucial to effectively tackle incidents and avert undesirable situations derived from pandemics. To this end, modelling and simulation combined with serious games emerge as a proper tool to train current and future strategic engineers on this subject. Thus, we propose a simulation-based serious game to devise and improve operational procedures and regulations aimed at preventing access to urban areas and key facilities. The multi-platform application considers three different types of game to explore different situations and evaluate user\u2019s proposal to face complex situations. In addition, we are still working on improving user experience and upgrading game mechanic

AI & Interoperable Simulation for Pandemics and Crisis Management

The adoption of Strategic Engineering as combined use of Artificial Intelligence, Simulation and Data Analytics to support decision making has a great potential in dealing with Pandemics due to their complexity and the impact of VUCA (Volatility, Uncertainty, Complexity & Ambiguity) on them. From this point of view using advanced paradigms such as MS2G and adopting interoperability standards is a major enabler to guarantee their effectiveness in dealing with these problems; this paper represents an introductory work on a joint research devoted to finalize experimentation and test to develop this new capability within Research Centers for supporting the Society during pandemic

Sphingolipids and plasma membrane hydrolases in human primary bronchial cells during differentiation and their altered patterns in cystic fibrosis

Human primary bronchial epithelial cells differentiated in vitro represent a valuable tool to study lung diseases such as cystic fibrosis (CF), an inherited disorder caused by mutations in the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator. In CF, sphingolipids, a ubiquitous class of bioactive lipids mainly associated with the outer layer of the plasma membrane, seem to play a crucial role in the establishment of the severe lung complications. Nevertheless, no information on the involvement of sphingolipids and their metabolism in the differentiation of primary bronchial epithelial cells are available so far. Here we show that ceramide and globotriaosylceramide increased during cell differentiation, whereas glucosylceramide and gangliosides content decreased. In addition, we found that apical plasma membrane of differentiated bronchial cells is characterized by a higher content of sphingolipids in comparison to the other cell membranes and that activity of sphingolipids catabolic enzymes associated with this membrane results altered with respect to the total cell activities. In particular, the apical membrane of CF cells was characterized by high levels of ceramide and glucosylceramide, known to have proinflammatory activity. On this basis, our data further support the role of sphingolipids in the onset of CF lung pathology