Technical, financial, and social barriers and challenges in deep building renovation: Integration of lessons learned from the H2020 cluster projects

With a low rate of new building construction and an insufficient rate of existing building renovation, there is the need to step up the pace of building renovation with ambitious performance targets to achieve European Union (EU) climate change policies for 2050. However, innovative technologies, including, but not limiting to, plug and play (PnP) prefabricated facades, information and communications technology (ICT)-support for building management systems (BMS), the integration of renewable energy systems (RES), building information model (BIM) and building performance simulation models (BPSM), advanced heating, ventilation, and air conditioning (HVAC), advanced geomatics, 3D-printing, and smart connectors, cannot alone solve the problem of low renovation rates of existing buildings in Europe that is hindering reaching of EU-wide targets. A workshop was held at the Sustainable Place Conference 2018 to present, with an integrative approach, the experiences from four H2020 innovation actions, i.e., 4RinEU, P2ENDURE, Pro-GET-OnE, and MORE-CONNECT, which were united by their central aims of improving building energy performance through deep renovation practices. This article presents the outcomes of the joint workshop and interactive discussion, by focusing on technical, financial, and social added values, barriers and challenges, in the context of the building renovation processes tackled by the four projects. Conclusive remarks converge on the identification of open questions to address future innovation opportunities, as well as some recommendations to be used at a policy level and/or in future implementation projects

The complex-formation behaviour of His residues in the fifth Cu2+ binding site of human Prion protein: a close look

Human Prion Protein (hPrPC) is able to bind up to six Cu2+ ions. Four of them can be allocated in the “octarepeat domain”, a region of the unstructured N-terminal domain containing four tandem-repetitions of the sequence PHGGGWGQ. It is widely accepted that the additional binding sites correspond to His-96 and His-111 residues. However, recent literature does not agree on the role and the behavior of these sites in Cu2+ complexation to hPrPC. In order to shed more light on this topic, some peptidic analogues of the PrP92-113 fragment were synthesized: (H96A)PrP92-113, (H111A)PrP92-113, (H96Nτ-Me-His)PrP92-113, (H111Nτ-Me-His)PrP92-113, (H96Nτ-Me-His)PrP92-100, (H111Nτ-Me-His)PrP106-113, where an alanine or a histidine methylated at the τ nitrogen atom of its imidazole ring have been substituted to His-96 or His-111. The first two ligands allowed to confirm that His-111 binding site is stronger than His-96 one: they act as independent sites even at Cu2+-ion substoichiometric levels. Neither multi-histidine binding nor bis-complex formation has been detected at neutral pH. Nτ methylation gave evidence that τ nitrogens of imidazole residues can participate in complex-formation only at acidic pH, where displacement of amidic protons by Cu2+ ions is not allowed. Finally, the length of the fragment does not look to have any significant influence on the behavior of the two His-96 and His-111 binding sites, from the point of view of neither the coordination geometry nor their relative strength

Thermodynamic and spectroscopic investigation on the role of Met residues in CuII binding to the non-octarepeat site of the human prion protein

Among the common features shared by neurodegenerative diseases there is the central role played by specific proteins or peptides which accumulate in neurons as insoluble plaques or tangles, containing abnormal amounts of redox-active metal ions, like copper and iron. In the case of transmissible spongiform encephalopathies (TSE), the involved protein is known as "prion protein" (PrPC) since "prions" (proteinaceous and infectious) are the agents which make TSE transmissible. It is widely accepted that PrPC, in its wild-type form, can bind up to six Cu-II ions, four of them in the so-called "octarepeat domain" and the others in the "fifth (non-octarepeat) binding-site". The latter domain contains two His residues, acting as anchoring sites for Cu-II ions, and other potential binding residues, such as Lys and Met. While it is widely accepted that Lys residues do not take part in complex-formation, the role of methionines is still debated. In order to shed light on this issue, some peptides have been synthesized, either directly mimicking the sequence of the second half of the fifth binding site of human-PrPC (apo-form) or analogues where Met residues have been substituted by n-leucine. In addition, a series of short peptides, containing both His and Met residues in different relative positions, have been investigated, for the sake of comparison. Spectroscopic results, including NMR spectra of systems containing Ni-II as a probe for the paramagnetic Cu-II ion, agree on the exclusion of any direct interaction between the sulphur atom of Met residues and the Cu-II ion already bound to His-imidazole side-chains. However, thermodynamic data show that Met-109 somewhat contributes to stability of complex species and this can be attributed to different electronic and steric effects

The complex-formation behaviour of His residues in the fifth Cu2+ binding site of human Prion protein: a close look

Human Prion Protein (hPrPC) is able to bind up to six Cu2+ ions. Four of them can be allocated in the ‘‘octarepeat domain’’, a region of the unstructured N-terminal domain containing four tandem-repetitions of the sequence PHGGGWGQ. It is widely accepted that the additional binding sites correspond to His-96 and His-111 residues. However, recent literature does not agree on the role and the behavior of these sites in Cu2+ complexation to hPrPC. In order to shed more light on this topic, some peptidic analogues of the PrP92–113 fragment were synthesized: (H96A)PrP92–113, (H111A)PrP92–113, (H96Nt-Me-His)PrP92–113, (H111Nt-Me-His)PrP92–113, (H96Nt-Me-His)PrP92–100, (H111Nt-Me-His)PrP106–113, where an alanine or a histidine methylated at the t nitrogen atom of its imidazole ring have been substituted to His-96 or His-111. The first two ligands allowed to confirm that His-111 binding site is stronger than His-96 one: they act as independent sites even at Cu2+ ion substoichiometric levels. Neither multihistidine binding nor bis-complex formation has been detected at neutral pH. Nt methylation gave evidence that t nitrogens of imidazole residues can participate in complex-formation only at acidic pH, where displacement of amidic protons by Cu2+ ions is not allowed. Finally, the length of the fragment does not appear to have any significant influence on the behavior of the two His-96 and His-111 binding sites, from the point of view of either the coordination geometry or their relative strength