From cluster databases to cloud storage: Providing transactional support on the cloud

Durant les últimes tres dècades, les limitacions tecnològiques (com per exemple la capacitat dels dispositius d'emmagatzematge o l'ample de banda de les xarxes de comunicació) i les creixents demandes dels usuaris (estructures d'informació, volums de dades) han conduït l'evolució de les bases de dades distribuïdes. Des dels primers repositoris de dades per arxius plans que es van desenvolupar en la dècada dels vuitanta, s'han produït importants avenços en els algoritmes de control de concurrència, protocols de replicació i en la gestió de transaccions. No obstant això, els reptes moderns d'emmagatzematge de dades que plantegen el Big Data i el cloud computing—orientats a millorar la limitacions pel que fa a escalabilitat i elasticitat de les bases de dades estàtiques—estan empenyent als professionals a relaxar algunes propietats importants dels sistemes transaccionals clàssics, cosa que exclou a diverses aplicacions les quals no poden encaixar en aquesta estratègia degut a la seva alta dependència transaccional. El propòsit d'aquesta tesi és abordar dos reptes importants encara latents en el camp de les bases de dades distribuïdes: (1) les limitacions pel que fa a escalabilitat dels sistemes transaccionals i (2) el suport transaccional en repositoris d'emmagatzematge en el núvol. Analitzar les tècniques tradicionals de control de concurrència i de replicació, utilitzades per les bases de dades clàssiques per suportar transaccions, és fonamental per identificar les raons que fan que aquests sistemes degradin el seu rendiment quan el nombre de nodes i / o quantitat de dades creix. A més, aquest anàlisi està orientat a justificar el disseny dels repositoris en el núvol que deliberadament han deixat de banda el suport transaccional. Efectivament, apropar el paradigma de l'emmagatzematge en el núvol a les aplicacions que tenen una forta dependència en les transaccions és fonamental per a la seva adaptació als requeriments actuals pel que fa a volums de dades i models de negoci. Aquesta tesi comença amb la proposta d'un simulador de protocols per a bases de dades distribuïdes estàtiques, el qual serveix com a base per a la revisió i comparativa de rendiment dels protocols de control de concurrència i les tècniques de replicació existents. Pel que fa a la escalabilitat de les bases de dades i les transaccions, s'estudien els efectes que té executar diferents perfils de transacció sota diferents condicions. Aquesta anàlisi contínua amb una revisió dels repositoris d'emmagatzematge de dades en el núvol existents—que prometen encaixar en entorns dinàmics que requereixen alta escalabilitat i disponibilitat—, el qual permet avaluar els paràmetres i característiques que aquests sistemes han sacrificat per tal de complir les necessitats actuals pel que fa a emmagatzematge de dades a gran escala. Per explorar les possibilitats que ofereix el paradigma del cloud computing en un escenari real, es presenta el desenvolupament d'una arquitectura d'emmagatzematge de dades inspirada en el cloud computing la qual s’utilitza per emmagatzemar la informació generada en les Smart Grids. Concretament, es combinen les tècniques de replicació en bases de dades transaccionals i la propagació epidèmica amb els principis de disseny usats per construir els repositoris de dades en el núvol. Les lliçons recollides en l'estudi dels protocols de replicació i control de concurrència en el simulador de base de dades, juntament amb les experiències derivades del desenvolupament del repositori de dades per a les Smart Grids, desemboquen en el que hem batejat com Epidemia: una infraestructura d'emmagatzematge per Big Data concebuda per proporcionar suport transaccional en el núvol. A més d'heretar els beneficis dels repositoris en el núvol en quant a escalabilitat, Epidemia inclou una capa de gestió de transaccions que reenvia les transaccions dels clients a un conjunt jeràrquic de particions de dades, cosa que permet al sistema oferir diferents nivells de consistència i adaptar elàsticament la seva configuració a noves demandes de càrrega de treball. Finalment, els resultats experimentals posen de manifest la viabilitat de la nostra contribució i encoratgen als professionals a continuar treballant en aquesta àrea.Durante las últimas tres décadas, las limitaciones tecnológicas (por ejemplo la capacidad de los dispositivos de almacenamiento o el ancho de banda de las redes de comunicación) y las crecientes demandas de los usuarios (estructuras de información, volúmenes de datos) han conducido la evolución de las bases de datos distribuidas. Desde los primeros repositorios de datos para archivos planos que se desarrollaron en la década de los ochenta, se han producido importantes avances en los algoritmos de control de concurrencia, protocolos de replicación y en la gestión de transacciones. Sin embargo, los retos modernos de almacenamiento de datos que plantean el Big Data y el cloud computing—orientados a mejorar la limitaciones en cuanto a escalabilidad y elasticidad de las bases de datos estáticas—están empujando a los profesionales a relajar algunas propiedades importantes de los sistemas transaccionales clásicos, lo que excluye a varias aplicaciones las cuales no pueden encajar en esta estrategia debido a su alta dependencia transaccional. El propósito de esta tesis es abordar dos retos importantes todavía latentes en el campo de las bases de datos distribuidas: (1) las limitaciones en cuanto a escalabilidad de los sistemas transaccionales y (2) el soporte transaccional en repositorios de almacenamiento en la nube. Analizar las técnicas tradicionales de control de concurrencia y de replicación, utilizadas por las bases de datos clásicas para soportar transacciones, es fundamental para identificar las razones que hacen que estos sistemas degraden su rendimiento cuando el número de nodos y/o cantidad de datos crece. Además, este análisis está orientado a justificar el diseño de los repositorios en la nube que deliberadamente han dejado de lado el soporte transaccional. Efectivamente, acercar el paradigma del almacenamiento en la nube a las aplicaciones que tienen una fuerte dependencia en las transacciones es crucial para su adaptación a los requerimientos actuales en cuanto a volúmenes de datos y modelos de negocio. Esta tesis empieza con la propuesta de un simulador de protocolos para bases de datos distribuidas estáticas, el cual sirve como base para la revisión y comparativa de rendimiento de los protocolos de control de concurrencia y las técnicas de replicación existentes. En cuanto a la escalabilidad de las bases de datos y las transacciones, se estudian los efectos que tiene ejecutar distintos perfiles de transacción bajo diferentes condiciones. Este análisis continua con una revisión de los repositorios de almacenamiento en la nube existentes—que prometen encajar en entornos dinámicos que requieren alta escalabilidad y disponibilidad—, el cual permite evaluar los parámetros y características que estos sistemas han sacrificado con el fin de cumplir las necesidades actuales en cuanto a almacenamiento de datos a gran escala. Para explorar las posibilidades que ofrece el paradigma del cloud computing en un escenario real, se presenta el desarrollo de una arquitectura de almacenamiento de datos inspirada en el cloud computing para almacenar la información generada en las Smart Grids. Concretamente, se combinan las técnicas de replicación en bases de datos transaccionales y la propagación epidémica con los principios de diseño usados para construir los repositorios de datos en la nube. Las lecciones recogidas en el estudio de los protocolos de replicación y control de concurrencia en el simulador de base de datos, junto con las experiencias derivadas del desarrollo del repositorio de datos para las Smart Grids, desembocan en lo que hemos acuñado como Epidemia: una infraestructura de almacenamiento para Big Data concebida para proporcionar soporte transaccional en la nube. Además de heredar los beneficios de los repositorios en la nube altamente en cuanto a escalabilidad, Epidemia incluye una capa de gestión de transacciones que reenvía las transacciones de los clientes a un conjunto jerárquico de particiones de datos, lo que permite al sistema ofrecer distintos niveles de consistencia y adaptar elásticamente su configuración a nuevas demandas cargas de trabajo. Por último, los resultados experimentales ponen de manifiesto la viabilidad de nuestra contribución y alientan a los profesionales a continuar trabajando en esta área.Over the past three decades, technology constraints (e.g., capacity of storage devices, communication networks bandwidth) and an ever-increasing set of user demands (e.g., information structures, data volumes) have driven the evolution of distributed databases. Since flat-file data repositories developed in the early eighties, there have been important advances in concurrency control algorithms, replication protocols, and transactions management. However, modern concerns in data storage posed by Big Data and cloud computing—related to overcome the scalability and elasticity limitations of classic databases—are pushing practitioners to relax some important properties featured by transactions, which excludes several applications that are unable to fit in this strategy due to their intrinsic transactional nature. The purpose of this thesis is to address two important challenges still latent in distributed databases: (1) the scalability limitations of transactional databases and (2) providing transactional support on cloud-based storage repositories. Analyzing the traditional concurrency control and replication techniques, used by classic databases to support transactions, is critical to identify the reasons that make these systems degrade their throughput when the number of nodes and/or amount of data rockets. Besides, this analysis is devoted to justify the design rationale behind cloud repositories in which transactions have been generally neglected. Furthermore, enabling applications which are strongly dependent on transactions to take advantage of the cloud storage paradigm is crucial for their adaptation to current data demands and business models. This dissertation starts by proposing a custom protocol simulator for static distributed databases, which serves as a basis for revising and comparing the performance of existing concurrency control protocols and replication techniques. As this thesis is especially concerned with transactions, the effects on the database scalability of different transaction profiles under different conditions are studied. This analysis is followed by a review of existing cloud storage repositories—that claim to be highly dynamic, scalable, and available—, which leads to an evaluation of the parameters and features that these systems have sacrificed in order to meet current large-scale data storage demands. To further explore the possibilities of the cloud computing paradigm in a real-world scenario, a cloud-inspired approach to store data from Smart Grids is presented. More specifically, the proposed architecture combines classic database replication techniques and epidemic updates propagation with the design principles of cloud-based storage. The key insights collected when prototyping the replication and concurrency control protocols at the database simulator, together with the experiences derived from building a large-scale storage repository for Smart Grids, are wrapped up into what we have coined as Epidemia: a storage infrastructure conceived to provide transactional support on the cloud. In addition to inheriting the benefits of highly-scalable cloud repositories, Epidemia includes a transaction management layer that forwards client transactions to a hierarchical set of data partitions, which allows the system to offer different consistency levels and elastically adapt its configuration to incoming workloads. Finally, experimental results highlight the feasibility of our contribution and encourage practitioners to further research in this area

A reinforcement learning path planning approach for range-only underwater target localization with autonomous vehicles

Underwater target localization using range-only and single-beacon (ROSB) techniques with autonomous vehicles has been used recently to improve the limitations of more complex methods, such as long baseline and ultra-short baseline systems. Nonetheless, in ROSB target localization methods, the trajectory of the tracking vehicle near the localized target plays an important role in obtaining the best accuracy of the predicted target position. Here, we investigate a Reinforcement Learning (RL) approach to find the optimal path that an autonomous vehicle should follow in order to increase and optimize the overall accuracy of the predicted target localization, while reducing time and power consumption. To accomplish this objective, different experimental tests have been designed using state-of-the-art deep RL algorithms. Our study also compares the results obtained with the analytical Fisher information matrix approach used in previous studies. The results revealed that the policy learned by the RL agent outperforms trajectories based on these analytical solutions, e.g. the median predicted error at the beginning of the target’s localisation is 17% less. These findings suggest that using deep RL for localizing acoustic targets could be successfully applied to in-water applications that include tracking of acoustically tagged marine animals by autonomous underwater vehicles. This is envisioned as a first necessary step to validate the use of RL to tackle such problems, which could be used later on in a more complex scenarios.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 893089. This work also received financial support from the Spanish Ministerio de Economía y Competitividad (SASES: RTI2018-095112-B-I00; BITER-ECO: PID2020-114732RB C31). This work acknowledges the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), and from the Generalitat de Catalunya ”Sistemas de Adquisicion Remota de datos y Tratamiento de la Informacion en el Medio Marino (SARTI-MAR)” 2017 SGR 376. We gratefully acknowledge the David and Lucile Packard Foundation.Peer ReviewedPostprint (author's final draft

Platform-portable reinforcement learning methods to localize underwater targets

In this study, we present a platform-portable deep reinforcement learning method that has been used as a path-planning system to localize underwater objects with autonomous vehicles.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 893089. This work also received financial support from the Spanish Ministerio de Economía y Competitividad (BITERECO: PID2020-114732RBC31). This work acknowledges the ’Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S).Peer ReviewedPostprint (author's final draft

Sprouty1 controls genitourinary development via its N-terminal tyrosine

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) is a group of diseases that include a broad spectrum of developmental defects of the genitourinary system. Mouse models indicate that perturbations of the GDNF-Ret signaling pathway are a major genetic cause of CAKUT. Sprouty1 is an intracellular Ret inhibitor whose mutation results in supernumerary kidneys, megaureters, and hydronephrosis in mice. Both the molecular mechanisms and the structural domains critical for Sprouty function are a matter of controversy, partly because studies pursuing this objective rely on ectopic overexpression in cell lines. A conserved N-terminal tyrosine has been frequently, but not always, identified as critical for their function in vitro. Methods: We have generated Sprouty1 knockin mice bearing a tyrosine-to-alanine substitution in position 53, corresponding to the conserved N-terminal tyrosine of Sprouty1. We have characterized development of the genitourinary systems of these mice via different methods, including the use of reporter mice expressing EGFP form the Ret locus, and whole mount cytokeratin staining. Results: Mice lacking this tyrosine grow ectopic ureteric buds that ultimately will form supernumerary kidneys, a phenotype indistinguishable to that of Sprouty1 knockout mice. Sprouty1 knockin mice also present megaureters and vesicoureteral reflux, caused by failure of ureters to separate from Wolffian ducts and migrate to their definitive position. Conclusions: Tyrosine 53 is absolutely necessary to convey Sprouty1 function during genitourinary development.This work was supported by grants BFU2010-47175-P and BFU2017-83646-P (AEI/FEDER, UE) from MINECO to ME. MV was supported by a predoctoral fellowship from AGAUR. CA was supported by a predoctoral fellowship from Universitat de Lleida. SC was supported by a Cofund action from the Marie Curie program of the EU. We are grateful to Dr. Sanjay Jain (Washington University, St Louis) for sharing RetEGFP mice, and to Dr. Tung-Tien Sun (New York University) for Uroplakin antibody. We thank Anna Macià (IRB Lleida) for her contribution to the initial development of this manuscript, as well as Marta Hereu, Maria Santacana, Mónica Domingo and Maria Carrele for their excellent technical assistance

Gulls living in cities as overlooked seed dispersers within and outside urban environments

The yellow-legged gull is an opportunistic and generalist bird that has colonised urban areas, where it has found very favourable trophic resources but also causes disturbance to humans and damage to infrastructure. Here, we investigated the potential role that gulls play in the dispersal of plants in Barcelona, a highly populated city of northeastern Spain. We analysed the stomach contents of 145 chicks collected in urban nests and reported the presence of seeds of 27 plant taxa. We then developed a plant dispersal model based on the movements of 20 GPS-tracked yellow-legged gulls breeding in the city of Barcelona. We estimated seed dispersal distances, seed shadows and per- centage of seeds reaching habitats suitable for seeds regurgitated in pellets and those excreted in faeces. Seven of the 27 plant taxa found in the stomachs were alien taxa to Spain. Average dispersal distances of plant seeds by gulls were around 700 m, but maximum dispersal distances reached up to 35 km. Dispersal distances and seed spatial patterns did not differ between faeces and pellet models, as most strongly depended on gull movements. About 95% of the seeds were dispersed within urban environments and between 20 and 30% reached suitable habitats for seed deposition (urban woodlands, green urban parks and urban grasslands). Urban gulls frequently dispersed seeds (including alien species) within urban habitats, both via direct consumption or via secondary dispersal after consuming granivorous birds that had ingested the seeds, such as pigeons or parakeets. Urban planning for Barcelona is based on native plant species, and thus, special attention should be paid to alien plants dispersed by birds, which could pose a risk to native biodiversity in urban ecosystems

Characterization of homologous and heterologous adaptive immune responses in porcine reproductive and respiratory syndrome virus infection

The present study characterized the homologous and heterologous immune response in type-I porcine reproductive and respiratory syndrome virus (PRRSV) infection. Two experiments were conducted: in experiment 1, eight pigs were inoculated with PRRSV strain 3262 and 84 days post-inoculation (dpi) they were challenged with either strain 3262 or strain 3267 and followed for the next 14 days (98 dpi). In experiment 2, eight pigs were inoculated with strain 3267 and challenged at 84 dpi as above. Clinical course, viremia, humoral response (neutralizing and non-neutralizing antibodies, NA) and virus-specific IFN-γ responses (ELISPOT) were evaluated all throughout the study. Serum levels of IL-1, IL-6, IL-8, TNF-α and TGF-β were determined (ELISA) after the second challenge. In experiment 1 primo-inoculation with strain 3262 induced viremia of ≤ 28 days, low titres of homologous NA but strong IFN-γ responses. In contrast, strain 3267 induced longer viremias (up to 56 days), higher NA titres (≤ 6 log2) and lower IFN-γ responses. Inoculation with 3267 produced higher serum IL-8 levels. After the re-challenge at 84 dpi, pigs in experiment 1 developed mostly a one week viremia regardless of the strain used. In experiment 2, neither the homologous nor the heterologous challenge resulted in detectable viremia although PRRSV was present in tonsils of some animals. Homologous re-inoculation with 3267 produced elevated TGF-β levels in serum for 7-14 days but this did not occur with the heterologous re-inoculation. In conclusion, inoculation with different PRRSV strains result in different virological and immunological outcomes and in different degrees of homologous and heterologous protection

Effectiveness of home-based exercise delivered by digital health in older adults : a systematic review and meta-analysis

regular physical exercise is essential to maintain or improve functional capacity in older adults. Multimorbidity, functional limitation, social barriers and currently, coronavirus disease of 2019, among others, have increased the need for home-based exercise (HBE) programmes and digital health interventions (DHI). Our objective was to evaluate the effectiveness of HBE programs delivered by DHI on physical function, health-related quality of life (HRQoL) improvement and falls reduction in older adults. systematic review and meta-analysis. community-dwelling older adults over 65 years. exercises at home through DHI. physical function, HRQoL and falls. twenty-six studies have met the inclusion criteria, including 5,133 participants (range age 69.5 ± 4.0-83.0 ± 6.7). The HBE programmes delivered with DHI improve muscular strength (five times sit-to-stand test, −0.56 s, 95% confidence interval, CI −1.00 to −0.11; P = 0.01), functional capacity (Barthel index, 5.01 points, 95% CI 0.24-9.79; P = 0.04) and HRQoL (SMD 0.18; 95% CI 0.05-0.30; P = 0.004); and reduce events of falls (odds ratio, OR 0.77, 95% CI 0.64-0.93; P = 0.008). In addition, in the subgroup analysis, older adults with diseases improve mobility (SMD −0.23; 95% CI −0.45 to −0.01; P = 0.04), and balance (SMD 0.28; 95% CI 0.09-0.48; P = 0.004). the HBE programmes carried out by DHI improve physical function in terms of lower extremity strength and functional capacity. It also significantly reduces the number of falls and improves the HRQoL. In addition, in analysis of only older adults with diseases, it also improves the balance and mobility

Role of the epithelial-mesenchymal transition-related circular RNA, circ-10720, in non-small-cell lung cancer

Background: Circular RNAs (circRNAs) are non-coding RNAs with a circular structure that have recently emerged as important regulators of tumorogenesis. Recently, several circRNAS, including circ-10720 have been related to epithelial-mesenchymal transition (EMT) process. In the present study, we have analyzed the role of circ-10720 in non-small-cell lung cancer (NSCLC) and studied its prognostic relevance in resected stage I-IIIa NSCLC patients. Methods: Circ-10720 expression was analyzed using a custom TaqMan assay in four NSCLC cell lines (HCC44, A549, H23 and H1299) and in the normal immortalized lung cell line BEAS2B. Silencing of circ10720 was performed using two custom siRNAs which were transfected using lipofectamine 2000. Protein levels were evaluated by Western blot and immunofluorescence. Wound healing and invasion assays were performed to evaluate the impact the circRNA on cell motility. Apoptosis was analyzed by evaluation of Caspase 3-7 activity and proliferation by MTS assay. Moreover, the expression levels of the circRNA were studied in 119 resected NSCLC patients. The expression in tumor tissue was correlated with the main clinicopathological characteristics and with time to relapse (TTR). Results: Circ-10720 was overexpressed in HCC44 and A549 and underexpressed in H23 and H1299 NSCLC cell lines in comparison to BEAS2B normal immortalized lung cell line. CircRNA knockdown in the two circ-10720 overexpressing cell lines was associated with a decrease of Vimentin (VIM) and an increase of E-cadherin (CDH1) protein levels, loss of mesenchymal phenotype, and a significant reduction of migration and invasion capacity. After silencing circ-10720, the apoptosis rate increased and the proliferation was significantly reduced. Furthermore, circ-10720 was upregulated in tumor vs. normal tissue from 119 resected NSCLC patients. In the group of patients not receiving adjuvant treatment, those with high levels of circ-10720 had a shorter TTR than those with low levels and emerged as an independent prognostic value in the multivariate analysis. In tumor tissue, circ-10720 levels positively correlated with the EMT gene Twist1 levels. Conclusions: Circ-10720 regulates EMT, apoptosis and proliferation and acts as a biomarker of relapse in NSCLC

RTP801 is involved in mutant huntingtin-induced cell death

RTP801 expression is induced by cellular stress and has a pro-apoptotic function in non-proliferating differentiated cells such as neurons. In several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, elevated levels of RTP801 have been observed, which suggests a role for RTP801 in neuronal death. Neuronal death is also a pathological hallmark in Huntington's disease (HD), an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Currently, the exact mechanisms underlying mutant huntingtin (mhtt)-induced toxicity are still unclear. Here, we investigated whether RTP801 is involved in (mhtt)-induced cell death. Ectopic exon-1 mhtt elevated RTP801 mRNA and protein levels in nerve growth factor (NGF)-differentiated PC12 cells and in rat primary cortical neurons. In neuronal PC12 cells, mhtt also contributed to RTP801 protein elevation by reducing its proteasomal degradation rate, in addition to promoting RTP801 gene expression. Interestingly, silencing RTP801 expression with short hairpin RNAs (shRNAs) blocked mhtt-induced cell death in NGF-differentiated PC12 cells. However, RTP801 protein levels were not altered in the striatum of Hdh(Q7/Q111) and R6/1 mice, two HD models that display motor deficits but not neuronal death. Importantly, RTP801 protein levels were elevated in both neural telencephalic progenitors differentiated from HD patient-derived induced pluripotent stem cells and in the putamen and cerebellum of human HD postmortem brains. Taken together, our results suggest that RTP801 is a novel downstream effector of mhtt-induced toxicity and that it may be relevant to the human disease

A dominant negative mutation uncovers cooperative control of caudal Wolffian duct development by Sprouty genes

The Wolffian ducts (WD) are paired epithelial tubules central to the development of the mammalian genitourinary tract. Outgrowths from the WD known as the ureteric buds (UB) generate the collecting ducts of the kidney. Later during development, the caudal portion of the WD will form the vas deferens, epididymis and seminal vesicle in males, and will degenerate in females. While the genetic pathways controlling the development of the UB are firmly established, less is known about those governing development of WD portions caudal to the UB. Sprouty proteins are inhibitors of receptor tyrosine kinase (RTK) signaling in vivo. We have recently shown that homozygous mutation of a conserved tyrosine (Tyr53) of Spry1 results in UB defects indistinguishable from that of Spry1 null mice. Here, we show that heterozygosity for the Spry1 Y53A allele causes caudal WD developmental defects consisting of ectopically branched seminal vesicles in males and persistent WD in females, without affecting kidney development. Detailed analysis reveals that this phenotype also occurs in Spry1+/- mice but with a much lower penetrance, indicating that removal of tyrosine 53 generates a dominant negative mutation in vivo. Supporting this notion, concomitant deletion of one allele of Spry1 and Spry2 also recapitulates the genital phenotype of Spry1Y53A/+ mice with high penetrance. Mechanistically, we show that unlike the effects of Spry1 in kidney development, these caudal WD defects are independent of Ret signaling, but can be completely rescued by lowering the genetic dosage of Fgf10. In conclusion, mutation of tyrosine 53 of Spry1 generates a dominant negative allele that uncovers fine-tuning of caudal WD development by Sprouty genes.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants BFU2017-83646-P (MINECO) and PID2020-114947 GB-I00 (MCIU) (both supported by funds from AEI/FEDER, UE) to ME. MV was supported by a predoctoral fellowship from AGAUR. GA and CA and GA are supported by a fellowship from Universitat de Lleida. SC was supported by a Cofund action from the Marie Curie program of the E