Evaluation and control of the in-plane stiffness of timber floors for the performance-based retrofit of URM buildings

The seismic response of existing un-reinforced masonry (URM) buildings is strongly dependent on the characteristics of wooden floors and, in particular, on their in-plane stiffness and on the quality of connection between the floors and the URM elements. It is generally well-recognized that an adequate inplane-stiffness and proper connections can significantly improve the three-dimensional response of these buildings, obtaining a better distribution and transfer of forces to the lateral load resisting walls. However, the extensive damage observed during past earthquakes on URM buildings of different types have highlighted serious shortcomings in typical retrofit interventions adopted in the past and based on stiffening the diaphragm. Recent numerical investigations have also confirmed that increasing the stiffness of the diaphragm is not necessarily going to lead to an improved response, but could actually result to detrimental effects. The evaluation of the in-plane stiffness of timber floors in their as-built and retrofitted configuration is still an open question and a delicate issue, with design guidelines and previous research results providing incomplete and sometimes controversial suggestions to practicing engineers involved in the assessment and/or retrofit of these type of structures. In this contribution, the role of the in-plane stiffness of timber floors in the seismic response of URM buildings is critically discussed, based on the relatively limited available experimental and numerical evidences. A framework for a performance-based assessment and retrofit strategy of URM buildings, capable of accounting for the effects of a flexible diaphragm on the response prior to and after the retrofit intervention, is then proposed. By controlling the in-plane stiffness of the diaphragm, adopting a specific strengthening (or weakening) intervention, the displacements, accelerations and internal force demands can be maintained within targeted levels. This will protect undesired local mechanisms and aim for a more appropriate hierarchy of strength within the whole system

Combining β-Carotene with 5-FU via Polymeric Nanoparticles as a Novel Therapeutic Strategy to Overcome uL3-Mediated Chemoresistance in p53-Deleted Colorectal Cancer Cells

: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Despite recent therapeutic advancements, resistance to 5-fluorouracil (5-FU) remains a major obstacle to the successful treatment of this disease. We have previously identified the ribosomal protein uL3 as a key player in the cell response to 5-FU, and loss of uL3 is associated with 5-FU chemoresistance. Natural products, like carotenoids, have shown the ability to enhance cancer cell response to drugs and may provide a safer choice to defeat chemoresistance in cancer. Transcriptome analysis of a cohort of 594 colorectal patients revealed a correlation between uL3 expression and both progression-free survival and response to treatment. RNA-Seq data from uL3-silenced CRC cells demonstrated that a low uL3 transcriptional state was associated with an increased expression of specific ATP-binding cassette (ABC) genes. Using two-dimensional (2D) and three-dimensional (3D) models of 5-FU-resistant CRC cells stably silenced for uL3, we investigated the effect of a novel therapeutic strategy by combining β-carotene and 5-FU using nanoparticles (NPs) as a drug delivery system. Our results indicated that the combined treatment might overcome 5-FU chemoresistance, inducing cell cycle arrest in the G2/M phase and apoptosis. Furthermore, the combined treatment significantly reduced the expression levels of analyzed ABC genes. In conclusion, our findings suggest that β-carotene combined with 5-FU may be a more effective therapeutic approach for treating CRC cells with low levels of uL3