41 research outputs found

    Towards the Energy Transition of the Building Stock with BIPV: Innovations, Gaps and Potential Steps for a Widespread Use of Multifunctional PV Components in the Building Envelope

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    The scenario that emerges from scientific research on the use of BIPV systems in architecture shows that photovoltaic technologies and systems have reached a significant development in production and installation, becoming a strategic approach in the field of energy efficiency and enabling a progressive decarbonisation of the building stock. Still, knowledge and methods of architectural integration are not fully developed, especially in Italy. The present paper reports the results of a research activity that, systematising the main criteria and indicators for assessing the integrability of BIPVs in architecture, has led to the development of BIPV Product and Case Study Catalogues that define an up-to-date state of the art on aspects of design and technological innovation using BIPV systems and components. Catalogues have been created with the objective of contributing to the growth of knowledge on the most up-to-date methods of design by implementing a ‘technology transfer’ from good practice, in which photovoltaic systems are an integral part of the design concept and construction techniques of the architecture. The analysis related to the production of BIPV systems and components and their application in architectural projects allows one to highlight the main critical factors in the diffusion throughout the country and to identify the main research demand arising from the specific national situation

    Modulation of Alpha-Synuclein Aggregation by Dopamine Analogs

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    The action of dopamine on the aggregation of the unstructured alpha-synuclein (α-syn) protein may be linked to the pathogenesis of Parkinson's disease. Dopamine and its oxidation derivatives may inhibit α-syn aggregation by non-covalent binding. Exploiting this fact, we applied an integrated computational and experimental approach to find alternative ligands that might modulate the fibrillization of α-syn. Ligands structurally and electrostatically similar to dopamine were screened from an established library. Five analogs were selected for in vitro experimentation from the similarity ranked list of analogs. Molecular dynamics simulations showed they were, like dopamine, binding non-covalently to α-syn and, although much weaker than dopamine, they shared some of its binding properties. In vitro fibrillization assays were performed on these five dopamine analogs. Consistent with our predictions, analyses by atomic force and transmission electron microscopy revealed that all of the selected ligands affected the aggregation process, albeit to a varying and lesser extent than dopamine, used as the control ligand. The in silico/in vitro approach presented here emerges as a possible strategy for identifying ligands interfering with such a complex process as the fibrillization of an unstructured protein

    EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

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    Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling

    Switching cytolytic nanopores into antimicrobial fractal ruptures by a single side chain mutation

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    Disruption of cell membranes is a fundamental host defense response found in virtually all forms of life. The molecular mechanisms vary but generally lead to energetically favored circular nanopores. Here, we report an elaborate fractal rupture pattern induced by a single side-chain mutation in ultrashort (8–11-mers) helical peptides, which otherwise form transmembrane pores. In contrast to known mechanisms, this mode of membrane disruption is restricted to the upper leaflet of the bilayer where it exhibits propagating fronts of peptide-lipid interfaces that are strikingly similar to viscous instabilities in fluid flow. The two distinct disruption modes, pores and fractal patterns, are both strongly antimicrobial, but only the fractal rupture is nonhemolytic. The results offer wide implications for elucidating differential membrane targeting phenomena defined at the nanoscale

    Biocomputing approaches to protein protein interactions in molecular medicine

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    Proteins rarely act alone. They often undertake biological functions as components of larger molecular machines characterized by intricate physic- ochemical dynamic connections. Current research efforts increasingly point to genome-wide screenings for protein complexes. These data have to be integrated with structural information in order to gain insights into functional aspects. In this context, computational studies play a crucial role, being able to complement experimental data. In this thesis, I have used computational methods to unravel key aspects of several pharmacologically relevant protein complexes, using increasingly sophisticated computational tools. By using molecular modeling and classical molecular dynamics, I have pre- dicted the atomic details of the protein complex formed by Granzyme B, a component of the immune system that could be exploited for the design of recombinant constructs effective in cancer therapy, and its in vivo inhibitor Serpin B9. The work has been carried out in collaboration with Prof. Barth at Fraunhofer Institute, RWTH - University of Aachen. Next, I have ap- plied protein-protein docking procedures to explore the possible binding poses between PARP10 and GSK3beta, two interacting proteins involved in cancer pathways. This work is in collaboration with Prof. LĂŒscher at the Clinics of RWTH Aachen University. Finally, in close collaboration with Dr. Adriana Pietropaolo (U. Catanzaro, Italy), I have investigated the conformational flexibility of the complex between the neurotrophin NGF, essential for neuron function and survival, and its receptor TrkA. This complex is relevant for Alzheimer’s therapy. The results show that the structure of the complex in solution may differ from that in the solid state (so far the only one available). The previously unrecognized structural information could be used to design NGF mimics and signaling modulators in Alzheimer’s therapy

    Biocomputing approaches to protein protein interactions in molecular medicine

    Get PDF
    Proteins rarely act alone. They often undertake biological functions as components of larger molecular machines characterized by intricate physic- ochemical dynamic connections. Current research efforts increasingly point to genome-wide screenings for protein complexes. These data have to be integrated with structural information in order to gain insights into functional aspects. In this context, computational studies play a crucial role, being able to complement experimental data. In this thesis, I have used computational methods to unravel key aspects of several pharmacologically relevant protein complexes, using increasingly sophisticated computational tools. By using molecular modeling and classical molecular dynamics, I have pre- dicted the atomic details of the protein complex formed by Granzyme B, a component of the immune system that could be exploited for the design of recombinant constructs effective in cancer therapy, and its in vivo inhibitor Serpin B9. The work has been carried out in collaboration with Prof. Barth at Fraunhofer Institute, RWTH - University of Aachen. Next, I have ap- plied protein-protein docking procedures to explore the possible binding poses between PARP10 and GSK3beta, two interacting proteins involved in cancer pathways. This work is in collaboration with Prof. LĂŒscher at the Clinics of RWTH Aachen University. Finally, in close collaboration with Dr. Adriana Pietropaolo (U. Catanzaro, Italy), I have investigated the conformational flexibility of the complex between the neurotrophin NGF, essential for neuron function and survival, and its receptor TrkA. This complex is relevant for Alzheimer’s therapy. The results show that the structure of the complex in solution may differ from that in the solid state (so far the only one available). The previously unrecognized structural information could be used to design NGF mimics and signaling modulators in Alzheimer’s therapy

    Eco-districts and Social Housing in Northern Europe

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    New districts and ‘eco-cities’ built between the '90s and 2000s in the Scandinavian countries and the UK, as well as in Germany, France, the Netherlands and in other European countries, represent a decisive overcoming of the experimental phase where the ecological housing was just an innovative approach limited to small pilot projects. In these districts the social housing is implemented according to percentages corresponding to the housing policies of the different countries. The role of technological choices and the characteristics of the building process have been crucial for building quality to reduce environmental impacts and to support and promote new ecologically oriented lifestyles and a wider social inclusion

    Environmental project and public space rehabilitation: the great project for the historic center of Naples Unesco World Heritage Site

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    “Historic Centre of Naples, World Heritage Site Enhancement” project has as its goal the rehabilitation of the oldest part of the historic center of Naples, one of the largest and most representative of Europe. The research reference field is placed on the level of strategic approach to the project and process management downstream of EU funding in large cities, with particular multidisciplinary relevance and urban issues of a complex nature. The scientific products of study, training and research were collected in Guidelines for the rehabilitation of public spaces and for sustainable performance of interventions on roads, walkways, squares and urban facilities

    Environmental project and public space rehabilitation: the great project for the historic center of naples Unesco world heritage site / Progetto ambientale e riqualificazione dello spazio pubblico: il grande progetto per il centro storico di Napoli sito Unesco

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    “Historic Centre of Naples, World Heritage Site Enhancement” project has as its goal the rehabilitation of the oldest part of the historic center of Naples, one of the largest and most representative of Europe. The research reference field is placed on the level of strategic approach to the project and process management downstream of EU funding in large cities, with particular multidisciplinary relevance and urban issues of a complex nature. The scientific products of study, training and research were collected in Guidelines for the rehabilitation of public spaces and for sustainable performance of interventions on roads, walkways, squares and urban facilities. / Il Grande Progetto “Centro Storico di Napoli, valorizzazione del sito UNESCO” ha come obiettivo la riqualificazione della parte piĂč antica del Centro Storico di Napoli, fra i piĂč estesi e rappresentativi d’Europa. L’ambito di riferimento dell’attivitĂ  di ricerca Ăš collocabile sul piano della impostazione strategica della gestione progettuale e processuale a valle di finanziamenti europei in cittĂ  di grandi dimensioni, con una rilevanza multidisciplinare, interscalare e con problematiche urbane di natura complessa. Gli esiti dell’attivitĂ  di studio, formazione e ricerca sono stati raccolti in Linee guida per gli interventi di riqualificazione sostenibile degli spazi pubblici finalizzate all’efficacia prestazionale degli interventi su assi viari, percorsi pedonali, piazze e attrezzature urbane

    Eco-quartieri e Social Housing nelle esperienze nord europee / Eco-districts and Social Housing in Northern Europe

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    I nuovi quartieri e le ‘eco-cities’ realizzate fra gli anni ’90 e 2000 nei paesi scandinavi e nel Regno Unito, oltre che in Germania, Francia, Olanda ed altre nazioni europee, rappresentano un deciso superamento della fase sperimentale secondo cui l’housing ecologico rappresentava un approccio innovativo ma circoscritto a progetti pilota di piccole dimensioni. In questi quartieri il social housing Ăš attuato secondo quote percentuali corrispondenti alle politiche per la casa dei diversi paesi. Il ruolo delle scelte tecnologiche e delle caratteristiche del processo edilizio Ăš stato determinante per la qualitĂ  degli interventi, per la riduzione degli impatti ambientali e per il sostegno a nuovi stili di vita ecologicamente orientati e di piĂč ampia inclusione sociale. New districts and ‘eco-cities’ built between the '90s and 2000s in the Scandinavian countries and the UK, as well as in Germany, France, the Netherlands and in other European countries, represent a decisive overcoming of the experimental phase where the ecological housing was just an innovative approach limited to small pilot projects. In these districts the social housing is implemented according to percentages corresponding to the housing policies of the different countries. The role of technological choices and the characteristics of the building process have been crucial for building quality to reduce environmental impacts and to support and promote new ecologically oriented lifestyles and a wider social inclusion
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