SIMPLIFIED ANALYTICAL/MECHANICAL PROCEDURE FOR THE RESIDUAL CAPACITY ASSESSMENT OF EARTHQUAKE-DAMAGED REINFORCED CONCRETE FRAMES

The series of recent catastrophic earthquakes worldwide have further emphasized the evident complexity and difficulty related to the evaluation of the post-earthquake seismic residual capacity of buildings. In the aftermath of a major seismic event, a fast, yet effective, safety evaluation procedure for earthquake-damaged buildings is critical to speed up and support the definition of emergency planning strategies, as well as to provide useful intel to the stakeholders and aid the decision-making process to enhance community resilience. Therefore, this paper aims to investigate the possible implementations of a procedure based on SLaMA (Simple Lateral Mechanism Analysis) methodology for the seismic assessment of damaged Reinforced Concrete (RC) frame buildings. The proposed procedure is based on the use of reduction coefficients for damaged structural members, in line with the FEMA 306 approach, and an update of the “hierarchy of strength” at the subassembly level by accounting for the earthquake-related damage. Results are compared against a numerical model in terms of a Capacity vs. Demand Safety Index” (IS-V or %New Building Standard, %NBS) and Expected Annual Losses (EAL). Moreover, the simplified procedure can be used to assess the feasibility and effects of a repair/retrofit solution. Results show that the proposed analytical procedure is able to estimate with reasonable accuracy, considering its simplified nature, and the performance of the building when compared to numerical analyses. Finally, the effect of the use of low-damage exoskeletons based on the PRESSS low-damage technology has been evaluated via the application of the Displacement-Based Retrofit procedure

DEVELOPMENT OF A HOLISTIC PARAMETRIC FRAMEWORK FOR MULTI-PERFORMANCE LIFE-CYCLE EVALUATION OF POST-TENSIONED TIMBER BUILDINGS

Catastrophic events and climate change represent major challenges for modern society, which calls for new solutions able to provide acceptable performances with low carbon footprint. The environmental impact of buildings, already accounting for 39% of Carbon Dioxide (CO2) emissions in the European Union (EU), becomes much more important in seismic prone areas, where buildings are vulnerable to extensive damage, significantly influencing the sustainability as well as the resilience of the entire community. The low-damage post-tensioned engineered timber structural system, also known as Pres-Lam (Prestressed Laminated timber), meets the need for a shift towards a damage-control approach while using sustainable materials. Beside the material choice, the design phase has a strong influence over the environmental impact along the life cycle of buildings. Hence, decision-making process has to take into account multiple aspects related to the proposed solution, that have to be combined into a comprehensive framework. This paper proposes a holistic parametric approach able to evaluate simultaneously the seismic performance and the environmental impact of three different Pres-Lam case studies, developing an integrated model within Rhino-Grasshopper platform using independently developed packages. The seismic response is assessed through a probabilistic approach, whereas the carbon footprint is estimated through the Life-Cycle Assessment (LCA) procedure using the extensive database of the Grasshopper plugin One Click LCA. Given the parametric nature of the framework, a wide range of solutions can be analysed to make the optimal choice, with the possibility to include also energy simulations and combine all the results within a Multi-Criteria Decision Analysis to guide the decisional process

Development of a holistic parametric framework for multi-performance evaluation of post-tensioned timber buildings

Catastrophic events and climate change represent major challenges for modern society, which calls for new solutions able to provide acceptable performances with low carbon footprint. In the European Union (EU), the building and construction sector accounts for 36% of the total EU operational energy, and 39% of Carbon Dioxide (CO2) emissions (GlobalABC, IEA, UN Environment Programme, 2019). This aspect becomes much more important in seismic-prone areas, where buildings are vulnerable to extensive damage which significantly impacts the sustainability of the environment as well as the resilience of the entire community (Menna et al., 2013). Indeed, recent catastrophic earthquakes have once again emphasized the mismatch between social expectations over the seismic performance of modern buildings, proving the need for a shift towards a damage-control approach using low-damage technologies. Post-tensioned engineered timber structural system, also known as Pres-Lam (Prestressed Laminated timber), meets the need for an outstanding seismic structural performance using sustainable materials (Palermo et al., 2005, Granello et al., 2020). Besides the material choice, the design phase has a strong influence over the environmental impact along the life-cycle of buildings; hence, the decision-making process has to take into account multiple aspects related to the proposed solution that has to be combined into a comprehensive framework. To date, numerous procedures have been proposed to evaluate the seismic performance and environmental impact in the construction sector (the second, using Life-Cycle Assessment (LCA) regulated by ISO 14040 and ISO 14044 (Caruso et al., 2017)), but these are rarely considered simultaneously. Thus, this paper proposes a holistic parametric approach able to assess those different aspects, developing an integrated model in Rhino-Grasshopper environment using independently developed packages. Seismic and environmental performance are evaluated for three different Pres-Lam case studies. The seismic response is assessed through a probabilistic approach, whereas the carbon footprint is estimated using the extensive environmental database of the Grasshopper plugin One Click LCA. Given the parametric nature of the framework, a wide range of solutions can be analyzed in order to make the optimal choice, with the possibility to include also energy simulations and combine all of the results within a Multi-Criteria Decision Analysis to guide the decisional process

Simplified Analytical/Mechanical Procedure for the Residual Capacity Assessment of Earthquake-Damaged Reinforced Concrete Frames

The series of recent catastrophic earthquakes worldwide have further emphasized the evident complexity and difficulty related to the evaluation of the post-earthquake seismic residual capacity of buildings. In the aftermath of a major seismic event, a fast, yet effective, safety evaluation procedure for earthquakedamaged buildings is critical to speed up and support the definition of emergency planning strategies, as well as to provide useful intel to the stakeholders and aid the decision-making process to enhance community resilience. Currently, state-of-the-art procedures for post-earthquake seismic assessment of buildings involve the use of non-linear static (pushover) analyses coupled with capacity reduction factors for plastic hinges’ response of damaged components, in terms of stiffness, strength, and ductility (e.g., FEMA 306). However, a standardized and easy-to-apply procedure, preferably analytical rather than numerical, that allows one to perform safety evaluation and loss assessment in either pre- and post-earthquake scenarios, has not been implemented yet. To achieve that goal, building on the recent developments at the international level, the analytical/mechanical SLaMA (Simple Lateral Mechanism Analysis) method, adopted by internationally recognized guidelines for the seismic assessment of existing buildings (NZSEE 2017) could be extended in order to develop a framework for pre- and post-earthquake safety evaluation and loss assessment of buildings. Therefore, this paper aims to investigate the possible implementations of a SLaMA-based procedure for the seismic assessment of damaged Reinforced Concrete (RC) frame buildings. The proposed procedure is based on the use of reduction factors for damaged structural members, in line with the FEMA 306 approach, and an update of the “hierarchy of strength” at the subassembly level when initial earthquake-related damage is considered. This way, the global force-displacement capacity curve of the structure in its either undamaged or damaged configuration can be evaluated. Finally, safety evaluation and loss assessment are carried out through simplified spectrum-based procedures, in terms of “Safety Index” (IS-V or %New Building Standard, %NBS) and Expected Annual Losses (EAL). An application of the SLaMA-based procedure is presented for a case-study building. By comparing the results of the undamaged and damaged configurations, higher seismic risk and economic losses are observed when cumulative damage is considered. The effectiveness of possible retrofit/repair interventions is also investigated. The proposed SLaMA-based procedure can be implemented within ad-hoc post-earthquake screening forms, supporting the decision-making process of both re-occupancy and repair/retrofit vs. demolition

Molecular Biology in Glioblastoma Multiforme Treatment

Glioblastoma (GBM, grade IV astrocytoma), the most frequently occurring primary brain tumor, presents unique challenges to therapy due to its location, aggressive biological behavior, and diffuse infiltrative growth, thus contributing to having disproportionately high morbidity and mortality [...

Drug repurposing for the treatment of glioblastoma multiforme

Abstract Background Glioblastoma Multiforme is the deadliest type of brain tumor and is characterized by very poor prognosis with a limited overall survival. Current optimal therapeutic approach has essentially remained unchanged for more than a decade, consisting in maximal surgical resection followed by radiotherapy plus temozolomide. Main body Such a dismal patient outcome represents a compelling need for innovative and effective therapeutic approaches. Given the development of new drugs is a process presently characterized by an immense increase in costs and development time, drug repositioning, finding new uses for existing approved drugs or drug repurposing, re-use of old drugs when novel molecular findings make them attractive again, are gaining significance in clinical pharmacology, since it allows faster and less expensive delivery of potentially useful drugs from the bench to the bedside. This is quite evident in glioblastoma, where a number of old drugs is now considered for clinical use, often in association with the first-line therapeutic intervention. Interestingly, most of these medications are, or have been, widely employed for decades in non-neoplastic pathologies without relevant side effects. Now, the refinement of their molecular mechanism(s) of action through up-to-date technologies is paving the way for their use in the therapeutic approach of glioblastoma as well as other cancer types. Short conclusion The spiraling costs of new antineoplastic drugs and the long time required for them to reach the market demands a profoundly different approach to keep lifesaving therapies affordable for cancer patients. In this context, repurposing can represent a relatively inexpensive, safe and fast approach to glioblastoma treatment. To this end, pros and cons must be accurately considered

Tackling the Behavior of Cancer Cells: Molecular Bases for Repurposing Antipsychotic Drugs in the Treatment of Glioblastoma

Glioblastoma (GBM) is associated with a very dismal prognosis, and current therapeutic options still retain an overall unsatisfactorily efficacy in clinical practice. Therefore, novel therapeutic approaches and effective medications are highly needed. Since the development of new drugs is an extremely long, complex and expensive process, researchers and clinicians are increasingly considering drug repositioning/repurposing as a valid alternative to the standard research process. Drug repurposing is also under active investigation in GBM therapy, since a wide range of noncancer and cancer therapeutics have been proposed or investigated in clinical trials. Among these, a remarkable role is played by the antipsychotic drugs, thanks to some still partially unexplored, interesting features of these agents. Indeed, antipsychotic drugs have been described to interfere at variable incisiveness with most hallmarks of cancer. In this review, we analyze the effects of antipsychotics in oncology and how these drugs can interfere with the hallmarks of cancer in GBM. Overall, according to available evidence, mostly at the preclinical level, it is possible to speculate that repurposing of antipsychotics in GBM therapy might contribute to providing potentially effective and inexpensive therapies for patients with this disease

PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer

Combined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategyin oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoproteomic profile modification(s) in response to combined MEK/mTOR inhibition in PTEN- loss contexts and identified JAK1/STAT3 activation as a potential mediator of synergistic interactions. Overall, our results show that PTEN-loss is a crucial determinant of synergistic interactions between MAPK and PI3K pathway inhibitors, potentially exploitable for the selection of cancer patients at the highest chance of benefit from combined therapeutic strategies