Numerical modelling of the seismic response of buildings with energy dissipators

The poor performance of many framed RC structures in recent strong earthquakes has alerted about the need of improving their seismic behavior especially when they are designed according to obsolete seismic codes. Sometimes, RC buildings show a low level of structural damping, important second order effects and low ductility of the connecting joints, among other defects. These characteristics allow proposing the use of energy dissipating devices for improving their seismic behavior, controlling their lateral displacements, providing additional damping and ductility. In this work, the nonlinear dynamic response of RC buildings with energy dissipating devices is studied using advanced computational techniques. A fully geometric and constitutive nonlinear model for the description of the dynamic behavior of framed structures is used. The model proposed for the structures and the dissipating devices is based on the geometrically exact formulation for beams which considers finite deformation and finite strains. The equations of motion of the system are expressed in terms of sectional forces and generalized strains and the dynamic problem is solved using the displacement based method formulated in the finite element framework. An appropriated version of Newmark’s integration scheme is used in updating the kinematics variables in a classical Newton type iterative scheme. Each material point of the cross section is assumed to be composed of several simple materials with their own constitutive laws developed in terms of the material description of the First Piola Kirchhoff stress vector. Appropriated constitutive laws for concrete and for steel reinforcements are provided. The simple mixing theory is used to treat the resulting composite. A specific finite element based on the beam theory is proposed for modeling the energy dissipating devices. Several constitutive descriptions in terms of force and displacements are provided for the dissipators. Special attention is paid to the development of local and global damage indices capable of describing the residual strength of the buildings. Finally, several numerical tests are carried out to validate the ability of the model to reproduce the nonlinear seismic response of RC buildings with energy dissipating devices.Peer ReviewedPostprint (published version

Solution-based synthesis and processing of Sn- and Bi-doped Cu3SbSe4 nanocrystals, nanomaterials and ring-shaped thermoelectric generators

Copper-based chalcogenides that comprise abundant, low-cost, and environmental friendly elements are excellent materials for a number of energy conversion applications, including photovoltaics, photocatalysis, and thermoelectrics (TE). In such applications, the use of solution-processed nanocrystal (NC) to produce thin films or bulk nanomaterials has associated several potential advantages, such as high material yield and throughput, and composition control with unmatched spatial resolution and cost. Here we report on the production of Cu3SbSe4 (CASe) NCs with tuned amounts of Sn and Bi dopants. After proper ligand removal, as monitored by nuclear magnetic resonance and infrared spectroscopies, these NCs were used to produce dense CASe bulk nanomaterials for solid state TE energy conversion. By adjusting the amount of extrinsic dopants, dimensionless TE figures of merit (ZT) up to 1.26 at 673 K were reached. Such high ZT values are related to an optimized carrier concentration by Sn doping, a minimized lattice thermal conductivity due to efficient phonon scattering at point defects and grain boundaries, and to an increase of the Seebeck coefficient obtained by a modification of the electronic band structure with the Bi doping. Nanomaterials were further employed to fabricate ring-shaped TE generators to be coupled to hot pipes and which provided 20 mV and 1 mW per TE element when exposed to a 160 °C temperature gradient. The simple design and good thermal contact associated with the ring geometry and the potential low cost of the material solution processing may allow the fabrication of TE generators with short payback times.Peer ReviewedPostprint (author's final draft

Inelastic analysis of geometrically exact rods

Postprint (published version

Ultrasound-Assisted Melt Extrusion of Polymer Nanocomposites

A review of the latest developments in ultrasound-assisted melt extrusion of polymer nanocomposites is presented. In general, the application of ultrasound waves during melt extrusion of polymer in the presence of nanoparticles results in a more homogeneous dispersion of the nanoparticles in the polymer matrix. In spite of this, a lack of understanding in the field has hindered the development of this processing technique. Based on the analysis of literature on the field, key aspects are identified for a better understanding of the physical and chemical effects of ultrasound waves and the fabrication of polymer nanocomposites by means of melt extrusion

Heat-killed Mycobacterium tuberculosis induces trained immunity in vitro and in vivo administered systemically or intranasally

Trained immunity (TI) represents a memory-like process of innate immune cells. TI can be initiated with various compounds such as fungal β-glucan or the tuberculosis vaccine, Bacillus Calmette-Guérin. Nevertheless, considering the clinical applications of harnessing TI against infections and cancer, there is a growing need for new, simple, and easy-to-use TI inducers. Here, we demonstrate that heat-killed Mycobacterium tuberculosis (HKMtb) induces TI both in vitro and in vivo. In human monocytes, this effect represents a truly trained process, as HKMtb confers boosted inflammatory responses against various heterologous challenges, such as lipopolysaccharide (Toll-like receptor [TLR] 4 ligand) and R848 (TLR7/8 ligand). Mechanistically, HKMtb-induced TI relies on epigenetic mechanisms in a Syk/HIF-1α-dependent manner. In vivo, HKMtb induced TI when administered both systemically and intranasally, with the latter generating a more robust TI response. Summarizing, our research has demonstrated that HKMtb has the potential to act as a mucosal immunotherapy that can successfully induce trained responses

Intravenous administration of BCG in mice promotes natural killer and T cell-mediated antitumor immunity in the lung

Intravesical administration of Bacillus Calmette-Guérin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing tuberculosis infection in animals. Here, we examine IV BCG in several preclinical lung tumor models. Our findings demonstrate that BCG inoculation reduced tumor growth and prolonged mouse survival in models of lung melanoma metastasis and orthotopic lung adenocarcinoma. Moreover, IV BCG treatment was well-tolerated with no apparent signs of acute toxicity. Mechanistically, IV BCG induced tumor-specific CD8+ T cell responses, which were dependent on type 1 conventional dendritic cells, as well as NK cell-mediated immunity. Lastly, we also show that IV BCG has an additive effect on anti-PD-L1 checkpoint inhibitor treatment in mouse lung tumors that are otherwise resistant to anti-PD-L1 as monotherapy. Overall, our study demonstrates the potential of systemic IV BCG administration in the treatment of lung tumors, highlighting its ability to enhance immune responses and augment immune checkpoint blockade efficacy

Sur8, a determinant protein in colorectal cancer tumor progression

Resumen del trabajo presentado en el 43rd Annual Meeting of the SEBBM, celebrado en Barcelona (España) del 19 al 21 de julio de 2021.Colorectal cancer (CRC) has the highest incidence rate in the Spanish population. The most important challenge consists on the discovery of efficient disease treatments, due to high mortality rates in highly developed stages. Sur8 is a scaffold protein that positively modulates ERK signaling pathway, which has a major role in the progression and metastasis in colorectal cancer. The main goals of our research are to determine the role that Sur8 plays in the development and progression of CRC and to analyze its possible therapeutic potential. For this purpose, our group has developed an inducible conditional mouse model msur8f/fVillinCreERT2. In order to determine Sur8 action in the colonic tissue, we have developed organoids from the colon epithelium of healthy mice and have analyzed gene expression pattern by an RNAseq approach. Sur8 KO affects oncogenic CRC transcription factors expression, as well as the modulation of some Wnt pathway regulators. In regard to miRNA data, we have observed deregulation of miRNAs related to CRC in Sur8 KO organoids. To determine the role that Sur8 plays in the development and progression of CRC, we have subjected our inducible conditional mice to chemical carcinogenesis and we have observed that Sur8 KO males display less and smaller tumors and do not present any adenocarcinoma. In addition, we have carried out Sur8 silencing in human CRC cell lines by infection with constitutive shRNA lentiviruses. We have observed that Sur8 silencing produces decreases of cell tumor proliferation, and reduction of p-ERK levels. Finally, we are evaluating the effects of putative therapeutic agents against Sur8 in human CRC cell lines. Concretely, we are testing Celastrol, which has been described that binds and blocks the action of Sur8 in vitro. We have observed that Celastrol treatment diminishes the cell tumor proliferation in this model. Altogether, our results indicate that Sur8 may have a determinant role in CRC progression and that Sur8 could be a potential molecular target for the design of novel strategies against CRC

Modelación del crecimiento de pollos de engorda criados en pastoreo o confinamiento

Objective: To evaluate the growth of pasture or confinement-raised broiler chickens, using the Gompertz, Logistic and Richards models, and identify the most appropriate. Methodology: One hundred ten straight-run broilers Ross 308 were distributed in two systems: pasture or confinement. Birds were weighed every week until 56 d of age. Three growth models (Gompertz, Logistic and Richards) were considered and compared based on three goodness of fit criteria (coefficient of determination, Akaike information criterion and Bayesian information criterion). Results: The initial (L) and exponential (K) growth rates of the Gompertz and Logistic models, respectively, were higher in confined birds (L = 0.1232, K = 0.0779) compared to those raised in pasture (L = 0.0944 , K = 0.0657). The maximum relative growth (K) of the Richards model was lower in chickens in confinement (0.0129) than in pasture system (0.0153). With the three models, higher asymptotic weights (WA) were estimated for confined chickens (3,967.1 to 9,095.5) compared to pasture birds (2,461.7 to 5,192.6). According to the criteria considered, the Richards model had the best fit. Implications of study: The results are only valid for straight-run Ross 308 broiler chickens and under the specified management conditions. Findings: The growth of pasture or confinement-raised broiler chickens can be described with the Gompertz, Logistic and Richards models, however, the latter has a better fit.Objetivo: Evaluar el crecimiento de pollos de engorda criados en pastoreo o confinamiento, mediante los modelos Gompertz, Logístico y Richards, e identificar el más adecuado. Metodología: Ciento diez pollos de engorda mixtos Ross 308 se distribuyeron en dos sistemas de crianza: pastoreo o confinamiento. Semanalmente se obtuvo el peso corporal de cada ave, hasta los 56 d de edad. Tres modelos de crecimiento (Gompertz, Logístico y Richards) fueron considerados y se compararon con base en tres criterios de bondad de ajuste (coeficiente de determinación, criterio de información de Akaike y criterio de información Bayesiano). Resultados: Las tasas de crecimiento inicial (L) y exponencial (K) de los modelos Gompertz y Logístico, respectivamente, fueron mayores en las aves en confinamiento (L = 0.1232, K = 0.0779) respecto a las criadas en pastoreo (L = 0.0944, K = 0.0657). El máximo crecimiento relativo (K) del modelo Richards fue menor en pollos en confinamiento (0.0129) que en pastoreo (0.0153). Con los tres modelos, se estimaron mayores pesos asintóticos (WA) para los pollos en confinamiento (3,967.1 a 9,095.5) respecto a las aves en pastoreo (2,461.7 a 5,192.6). De acuerdo a los criterios considerados, el modelo Richards es el que tiene un mejor ajuste.         Implicaciones del estudio: Los resultados obtenidos sólo son válidos para pollos de engorda mixtos Ross 308 y bajo las condiciones de manejo especificadas. Conclusión: El crecimiento de pollos de engorda criados en confinamiento o pastoreo, puede describirse con los modelos Gompertz, Logístico y Richards, sin embargo, este último tiene un mejor ajuste

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None.We would like to acknowledge the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular”, from the sub-program RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund “A way to make Europe”, groups RD16/0011/0001, -/0002, -/005, -/0013, -/0015, -/0029), the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain and AvanCell-CM (Red de Investigación de Terapia Celular de la Comunidad de Madrid, Spain), for supporting some personnel and networking activities