Numerical Model Validation for Detection of Surface Displacements over Twin Tunnels from Metro Line 1 in the Historical Area of Seville (Spain)

In order to solve connectivity problems in metropolitan areas, the development of underground metro lines constitutes an unquestionable requirement. However, the construction work thereof encounters unfavourable circumstances when surface excavations must be carried out that cross historical areas of the city, due to the need to control surface movements. The design of the metro in the city of Seville (Spain) from 2004 to 2006 provides a representative example of this situation and triggered major upheavals that exerted repercussions on historical buildings. For these reasons, the excavation stages of Line 1 of this metro have been simulated by numerical methods using FLAC3D software and validated with the results provided by the real conditions. Consequently, various surface settlements have been evaluated by taking not only variates of the main parameters that characterise the soil of Seville, but also of the various load situations and excavation conditions. Notable results have been achieved through calibration of 54 variants of the same model corresponding to Line 1, and their comparison with the real results obtained in nine critical areas of the itinerary. The results obtained have made it possible to determine the effects of excavation on the subsoil of the city of Seville with great accuracy, since the percentage error of calculated vertical surface movements varies from 0.1% to 5.3%

Evaluation of open geotechnical knowledge in urban environments for 3D modelling of the city of Seville (Spain)

The need for sustainable urban growth management and preventive conservation of built elements constitute the key factors in today’s increasing demand for the better understanding of subsoil. This information, mainly available from geotechnical surveys, can be integrated into spatial databases to produce operational models. Aiming to generate strategies that enable the visualisation of underground properties in highly anthropised environments, the following four-phase methodology has been proposed: (a) Gathering of geotechnical data; (b) Spatial and statistical analysis; (c) Database design; (d) Generation of 2D and 3D models. Following the aforementioned criteria and using open sources, a spatial dataset of 650 points located within the historical centre of Seville (Spain) has been developed. This urban area is characterised by the heterogeneous distribution of its soil layers and their geotechnical properties. The results show that the application of this method enables a prompt and efficient display of the distribution of geotechnical layers in urban and metropolitan environments, by considering the variations in their mechanical properties. This simplified approach therefore establishes a new starting point for the development of predictive strategies based on approaches of a more complex nature that facilitate the analysis of the interactions between subsoil, buildings, and infrastructures

Action protocols for seismic evaluation of structures and damage restoration of residential buildings in Andalusia (Spain): “IT-Sismo” APP

The seismotectonic conditions of the Iberian Peninsula trigger the occurrence of earthquakes with an occasional periodicity, but with intensities greater than VI on the European macroseismic scale (EMS). For this reason, local action protocols are required in order to efficiently organise the technical inspections that must be carried out on a massive scale after events such as the earthquakes experienced in the Spanish cities of Lorca (2011) and Melilla (2016). This paper proposes the development of a set of documents for the evaluation and diagnosis of the state of existing buildings and infrastructure regarding seismic activity in Andalusia. With special attention paid to residential typology, approximations have been carried out to the normative context, to general comparatives, to particular analyses of a case studies selection, and to complementary approaches. The results have led to the establishment of two specific protocols. Firstly, the short-term guideline enables the classification of damage and risk levels, and the determination of what immediate interventions should be carried out through the generation of a preliminary on-site report. This activity can be performed by architects and engineers with the help of a mobile-device application (APP IT-Sismo Andalucía). Additionally, a long-term protocol provides calculation procedures and constructive solutions for the improvement of the seismic behaviour of affected buildings. Specially designed tests demonstrate the validity of the protocols and illustrate the need for information and communication technologies (ICT) tools in the evaluation of architectonic technical aspects.Programa Operativo FEDER de Andalucía 2007- 2013V Plan Propio de Investigación of the University of Sevill

Proyecto de guía para la rehabilitación sísmica de edificios e infraestructuras existentes en Andalucía

Los terremotos siguen provocando numerosas víctimas en España pese a contar con una normativa específica desde 1962. La aceleración sísmica del terremoto acaecido en Lorca en 2011 superó el doble de la prevista en la actual NCSE-02. Sin embargo, la principal causa de los daños no fue consecuencia del colapso estructural, sino de deficiencias constructivas. La actual crisis económica sugiere que el parque edificado va a tener una vida útil muy superior a la prevista. Por tanto, con objeto de evitar futuras pérdidas humanas y disminuir daños tras la acción de un terremoto, se está realizando un Protocolo de Actuación para edificios e infraestructuras existentes que contará con dos partes: “clasificación de daños e intervenciones inmediatas” y “procedimientos de cálculo y soluciones constructivas para mejorar el comportamiento sísmico”. La primera parte de este Protocolo irá implementada con una aplicación informática que realizará un Informe previo sobre el grado de afección del edificio, acompañado de fotografías, croquis y una descripción de daños. La segunda parte propondrá coeficientes de seguridad, sistemas de comprobación y detalles constructivos para verificar y aumentar la seguridad de los edificios frente a sismo

Study of the impact of an online self-assessment questionnaire for the treatment of measurement uncertainties

La correcta comprensión del origen de las incertidumbres experimentales, así como su tratamiento matemático, resulta fundamental en la formación de cualquier científico, pues permite determinar la precisión de los resultados experimentales. Por este motivo, estos conocimientos forman parte de las competencias relacionadas con las asignaturas de Física de los primeros cursos universitarios. Se ha desarrollado e implantado en la plataforma Moodle un cuestionario de autoevaluación online como actividad de autoaprendizaje enfocada al tratamiento de errores en las prácticas de laboratorio de las asignaturas de Física de primer curso en diferentes grados científico-técnicos. Concretamente, fueron puestos a disposición del alumnado de los Grados de Química y Ciencia y Tecnología de los Alimentos. Para valorar el impacto percibido por el alumnado de estos cuestionarios de autoevaluación se realizaron encuestas previas y posteriores a las actividades, cuyos resultados muestran una alta correlación entre el uso de la actividad y la percepción de su utilidad. De igual forma, se han analizado las estadísticas de uso y las calificaciones proporcionadas por la plataforma Moodle, mostrando que, pese a la positiva percepción del impacto del cuestionario en su aprendizaje, es necesario perfilar la actividad para conseguir un mayor grado de uso.The correct understanding of the origin of the experimental uncertainties and their mathematical treatment is fundamental in the formation of any scientist, since it allows to determine the precision of the experimental results. For this reason, such knowledge is usually part of the competences related to the Physics subjects of the first university courses. An online self-assessment questionnaire was developed and implemented in the Moodle platform as a self-learning activity focused on the treatment of errors in the laboratory practices of the first year Physics subjects in different scientific-technical degrees. Specifically, it was available to students from Chemistry and Food Science and Technology degrees. To assess the impact perceived by students, surveys were conducted before and after the activities. The analysis of the answers given to those surveys, used as indicators of the perceived impact of the activity, show a high correlation between the use of the activity and the perception of its usefulness. Similarly, usage statistics and the ratings provided by the Moodle platform were analyzed, showing that, despite the positive perception of the impact of the questionnaire on their learning, it is necessary to improve the activity to achieve a greater degree of use

Genetic Study of SARS-CoV-2 Non Structural Protein 12 in COVID-19 Patients Non Responders to Remdesivir

Remdesivir (RDV) was the first antiviral drug approved by the FDA to treat severe coronavirus disease-2019 (COVID-19) patients. RDV inhibits SARS-CoV-2 replication by stalling the non structural protein 12 (nsp12) subunit of the RNA-dependent RNA polymerase (RdRp). No evidence of global widespread RDV-resistance mutations has been reported, however, defining genetic pathways to RDV resistance and determining emergent mutations prior and subsequent antiviral therapy in clinical settings is necessary. This study identified 57/149 (38.3%) patients who did not respond to one course (5-days) (n = 36/111, 32.4%) or prolonged (5 to 20 days) (n = 21/38, 55.3%) RDV therapy by subgenomic RNA detection. Genetic variants in the nsp12 gene were detected in 29/49 (59.2%) non responder patients by Illumina sequencing, including the de novo E83D mutation that emerged in an immunosuppressed patient after receiving 10 + 8 days of RDV, and the L838I detected at baseline and/or after prolonged RDV treatment in 9/49 (18.4%) non responder subjects. Although 3D protein modeling predicted no interference with RDV, the amino acid substitutions detected in the nsp12 involved changes on the electrostatic outer surface and in secondary structures that may alter antiviral response. It is important for health surveillance to study potential mutations associated with drug resistance as well as the benefit of RDV retreatment, especially in immunosuppressed patients and in those with persistent replication. IMPORTANCE This study provides clinical and microbiologic data of an extended population of hospitalized patients for COVID-19 pneumonia who experienced treatment failure, detected by the presence of subgenomic RNA (sgRNA). The genetic variants found in the nsp12 pharmacological target of RDV bring into focus the importance of monitoring emergent mutations, one of the objectives of the World Health Organization (WHO) for health surveillance. These mutations become even more crucial as RDV keeps being prescribed and new molecules are being repurposed for the treatment of COVID-19. The present article offers new perspectives for the clinical management of non responder patients treated and retreated with RDV and emphasizes the need of further research of the benefit of combinatorial therapies and RDV retreatment, especially in immunosuppressed patients with persistent replication after therapy.This work was financed by a Gilead Sciences grant (IN-ES-540-6089) and CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, España (CB21/13/00081). This work was financed by ad hoc patronage funds for research on COVID-19 from donations from citizens and organizations to the Hospital Clínic de Barcelona-Fundació Clínic per a la Recerca Biomèdica.S

Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting

26 p.-6 fig.-1 tab.-1 graph. abst.There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)—the principal methyl donor—acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.M.V.-R. is supported by Proyecto PID2020-119486RB-100 (funded by MCIN/AEI/10.13039/501100011033), Gilead Sciences International Research Scholars Program in Liver Disease, Acción Estratégica Ciberehd Emergentes 2018 (ISCIII), Fundación BBVA, HORIZON-TMA-MSCA-Doctoral Networks 2021 (101073094), and Redes de Investigación 2022 (RED2022-134485-T). M.L.M.-C. is supported by La CAIXA Foundation (LCF/PR/HP17/52190004), Proyecto PID2020-117116RB-I00 (funded by MCIN/AEI/10.13039/501100011033), Ayudas Fundación BBVA a equipos de investigación científica (Umbrella 2018), and AECC Scientific Foundation (Rare Cancers 2017). A.W. is supported by RTI2018-097503-B-I00 and PID2021-127169OB-I00, (funded by MCIN/AEI/10.13039/501100011033) and by “ERDF A way of making Europe,” Xunta de Galicia (Ayudas PRO-ERC), Fundación Mutua Madrileña, and European Community’s H2020 Framework Programme (ERC Consolidator grant no. 865157 and MSCA Doctoral Networks 2021 no. 101073094). C.M. is supported by CIBERNED. P.A. is supported by Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT1476-22), PID2021-124425OB-I00 (funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe,” MCI/UE/ISCiii [PMP21/00080], and UPV/EHU [COLAB20/01]). M.F. and M.G.B. are supported by PID2019-105739GB-I00 and PID2020-115472GB-I00, respectively (funded by MCIN/AEI/10.13039/501100011033). M.G.B. is supported by Xunta de Galicia (ED431C 2019/013). C.A., T.L.-D., and J.B.-V. are recipients of pre-doctoral fellowships from Xunta de Galicia (ED481A-2020/046, ED481A-2018/042, and ED481A 2021/244, respectively). T.C.D. is supported by Fundación Científica AECC. A.T.-R. is a recipient of a pre-doctoral fellowship from Fundación Científica AECC. S.V.A. and C.R. are recipients of Margarita Salas postdoc grants under the “Plan de Recuperación Transformación” program funded by the Spanish Ministry of Universities with European Union’s NextGeneration EU funds (2021/PER/00020 and MU-21-UP2021-03071902373A, respectively). T.C.D., A.S.-R., and M.T.-C. are recipients of Ayuda RYC2020-029316-I, PRE2019/088960, and BES-2016/078493, respectively, supported by MCIN/AEI/10.13039/501100011033 and by El FSE invierte en tu futuro. S.L.-O. is a recipient of a pre-doctoral fellowship from the Departamento de Educación del Gobierno Vasco (PRE_2018_1_0372). P.A.-G. is recipient of a FPU pre-doctoral fellowship from the Ministry of Education (FPU19/02704). CIC bioGUNE is supported by Ayuda CEX2021-001136-S financiada por MCIN/AEI/10.13039/501100011033. A.B.-C. was funded by predoctoral contract PFIS (FI19/00240) from Instituto de Salud Carlos III (ISCIII) co-funded by Fondo Social Europeo (FSE), and A.D.-L. was funded by contract Juan Rodés (JR17/00016) from ISCIII. A.B.-C. is a Miguel Servet researcher (CPII22/00008) from ISCIII.Peer reviewe