Climate-induced conservation risks of historic reinforced concrete buildings: Preliminary results from literature review

Environmental conditions can favour different kinds of deterioration in historic reinforced concrete structures. This preliminary results from literature review are focused on the climate-induced risks affecting reinforced concrete buildings with respect to mechanical, chemical, and biological deterioration. To this purpose, a three-step process defined by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram, was used leading to the inclusion of 45 documents identified via the search engines Scopus and Web of Science. The outcomes highlight that chemical and mechanical decays are the most investigated ones, being mainly triggered by salt weathering and freezing-thawing cycles. It was found that experimental and theoretical approaches are often coupled to estimate climate-induced deterioration mechanisms, also considering environmental parameters. Finally, the literature search provides some milestones which can be used to evaluate gaps and research needs in the field of climate-induced conservative risks affecting reinforced concrete structures

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2H)-one as Novel Scaffold for FABP4 Inhibition

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series

contribution of individual amino acids within mhc molecule or antigenic peptide to tcr ligand potency

The TCR recognition of peptides bound to MHC class II molecules is highly flexible in some T cells. Although progress has been made in understanding the interactions within the trimolecular complex, to what extent the individual components and their amino acid composition contribute to ligand recognition by individual T cells is not completely understood. We investigated how single amino acid residues influence Ag recognition of T cells by combining several experimental approaches. We defined TCR motifs for CD4+ T cells using peptide synthetic combinatorial libraries in the positional scanning format (PS-SCL) and single amino acid-modified peptide analogues. The similarity of the TCR motifs defined by both methods and the identification of stimulatory antigenic peptides by the PS-SCL approach argue for a contribution of each amino acid residue to the overall potency of the antigenic peptide ligand. In some instances, however, motifs are formed by adjacent amino acids, and their combined influence is superimposed on the overall contribution of each amino acid within the peptide epitope. In contrast to the flexibility of the TCR to interact with different peptides, recognition was very sensitive toward modifications of the MHC-restriction element. Exchanges of just one amino acid of the MHC molecule drastically reduced the number of peptides recognized. The results indicate that a specific MHC molecule not only selects certain peptides, but also is crucial for setting an affinity threshold for TCR recognition, which determines the flexibility in peptide recognition for a given TCR

Optimization of 4-amino-pyridazin-3(2H)-one as a valid core scaffold for FABP4 inhibitors

Current clinical research suggests that fatty acid-binding protein 4 inhibitors (FABP4is), which are of biological and therapeutic interest, may show potential in treating cancer and other illnesses. We sought to uncover new structures through the optimization of the previously reported 4-amino and 4-ureido pyridazinone-based series of FABP4is as part of a larger research effort to create more potent FABP4 inhibitors. This led to the identification of 14e as the most potent analog with IC₅₀ = 1.57 μM, which is lower than the IC₅₀ of the positive control. Advanced modeling investigations and in silico absorption, distribution, metabolism, and excretion - toxicity calculations suggested that 14e represents a potential candidate for in vivo studies such as FABP4i