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Advanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on genes, cells and tissues. The first ATMP received marketing authorization in Europe in 2009, whereas Brazil granted the first authorization in 2020. The objective of this study was to compare the regulatory models adopted by Brazil, the USA, Japan and the European Union, which comprise the member countries of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, with regard to the marketing authorization of ATMPs.The authors performed a review of the scientific literature and official documents of the regulatory agencies in the aforementioned countries.The legislation and regulatory guidelines adopted by the regulatory agencies exhibit similarities and differences. It was not possible to assess whether these differences can be translated into divergent final recommendations by regulatory authorities upon a request for marketing authorization.In the future, it will be appropriate to start a progressive process of harmonization between these agencies in terms of terminology, legal recommendations and characterization requirements. This is particularly important for emerging countries such as Brazil. In this sense, some measures can be taken to achieve alignment between regulators.

The textile industry is essential, but it is also responsible for causing environmental problems, particularly the discharge of dyes. In this context, this study aimed to immobilize a previously purified peroxidase, called MoPOX, on glutaraldehyde-activated chitosan beads in order to improve the potential for textile dye decolorization. The chitosan beads were activated with 8% glutaraldehyde for 1 h, and the immobilization was performed at 30 °C, pH 5.2 for 4 h. Scanning Electron Microscopy (SEM) analyses were used to observe the differences in the chitosan beads after immobilization. The optimum temperature dropped from 70 °C to 30 °C after immobilization, but immobilized MoPOX demonstrated excellent heat stability. The optimum pH remained 5.2, while the apparent kinetic constant value (Km) of immobilized MoPOX (14.67 mM) was lower in comparison to free MoPOX (46.8 mM). The immobilized enzyme showed improved activity after long storage times, and it could retain 40 % of its original activity even after 5 cycles. The potential for decolorization of different textile dyes was considerably enhanced after immobilization, reaching more than 80 %. Also, MoPOX showed no toxicity towards Artemia salina. Overall, the findings point to the promising potential of using immobilized MoPOX as a biocatalyst in a variety of biotechnological applications.

We explore the feasibility of using FOS and JUN gene expression and ATR-FTIR for diagnosis of thyroid cancer. For the study, 38 samples (6 non-neoplastic (NN), 10 papillary thyroid carcinoma (PTC), 7 follicular thyroid carcinoma (FTC), and 15 benign tumors (BT) were subjected to RNA extraction followed by quantitative real time PCR (qRT-PCR) and 30 samples (5 NN, 9 PTC, 5 FTC, and 11 benign) were used for Attenuated Total Reflectance – Fourier Transform Infrared (ATR-FTIR) followed by multivariate analysis. We found FOS and JUN expression in malignant tumor samples to be significantly lower than NN and benign. ATR-FTIR after multivariate analysis could identify the difficult to diagnose PTC with 93% efficiency. Overall, results suggest the diagnostic potential of molecular biology techniques combined with ATR-FTIR spectroscopy in differentiated thyroid carcinomas (PTC and FTC) and benign tumors.

Made available in DSpace on 2022-04-29T08:32:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Background & aim: Probiotics in the gut have been suggested to have a beneficial effect on anxiety response and depressive disorder. Hence we conducted a systematic review and meta-analysis to summarize the effects of probiotics associated with or without pharmacological or psychological therapies in patients with depressive and/or anxiety symptoms or disorders. Methods: We conducted searches of MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, ProQuest, LILACS, and Web of Science up to February 2020 to identify randomized controlled trials (RCTs) investigating the efficacy of probiotics associated with or without pharmacological or psychological therapies for patient-important outcomes including relief of depressive, anxiety and stress symptoms, cognitive functions, adverse events and quality of life. We used the GRADE approach to rate the overall certainty of the evidence by outcome. The protocol of the systematic review was registered with PROPSERO and published under the number CRD4202016329. Results: 16 RCTs including 1,125 patients proved eligible. Results suggested a significant improvement in using Beck Depression Index (MD, −3.20 [95% CI, −5.91 to −0.49], p = 0.02; I2 = 21%, p = 0.28) for depression symptoms and State-Trait Anxiety Inventory (STAI) (MD, −6.88 [95% CI, −12.35 to −1.41], p = 0.01; I2 = 24%, p = 0.25) for anxiety with overall certainty in evidence rated as moderate and low, respectively. However, Depression Scale (DASS-Depression) (MD, 2.01 [95% CI, −0.80 to 4.82], p = 0.16; I2 = 0%, p = 0.62), Montgomery-Asberg Depression Rating Scale (MADRAS) (MD, −2,41 [95% CI, −10,55 to 5,72], p = 0,56; I2 = 87%, p = 0,006), Anxiety scale (DASS-Anxiety) (MD, 0.49 [95% CI, −4.05 to 5.02], p = 0.83; I2 = 74%, p = 0.05), and Stress Scale (DASS-Stress) (MD, 0.84 [95% CI, −2.64 to 4.33], p = 0.64; I2 = 34%, p = 0.22) showed no significant decrease in the relief of depression, anxiety and stress symptoms of probiotics compared to placebo with overall certainty in evidence rated as very low for all outcomes. We also found no differences in the Beck Anxiety Index (BAI) (MD, −3.21 [95% CI, −6.50 to 0.08], p = 0.06; I2 = 0%, p = 0.88) with overall certainty in evidence rated as low. Results suggested a non-statistically significantly effect of probiotics in the adverse events outcomes. Conclusions: The current review suggests that probiotics may improve symptoms of depression and anxiety in clinical patients. However, given the limitations in the included studies, RCTs with long-term follow-up and large sample sizes are needed. Department of Biosciences and Oral Diagnosis Institute of Science and Technology Universidade Estadual Paulista McMaster Institute of Urology McMaster University St. Joseph's Healthcare Department of Community Medicine & School of Public Health PGIMER Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Botucatu Medical School São Paulo State University (Unesp) Universidade Anhembi-Morumbi Campus São José Dos Campos School of Dentistry Universidade Mogi Das Cruzes High Institute of Public Health-Alexandria University Drug Information Center Tanta Chest Hospital Universidade Do Vale Do Paraíba Departament of Preventive Medicine Faculdade de Medicina - FMUSP Universidade de Sao Paulo Department of Surgical Specialties and Anesthesiology Department Botucatu Medical School UNESP - Universidade Estadual Paulista Department of Biosciences and Oral Diagnosis Institute of Science and Technology Universidade Estadual Paulista Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Botucatu Medical School São Paulo State University (Unesp) Department of Surgical Specialties and Anesthesiology Department Botucatu Medical School UNESP - Universidade Estadual Paulista

A durable goods monopolist proposes selling mechanisms in two periods, being unable to commit in the first period on the mechanism to propose in the second. Trade is anonymous and resale is not possible. Although buyers have a continuum of possible valuations, the optimal first-period mechanism is a menu with at most two possibilities: a high price guaranteeing delivery and a low price subject to rationing. This characterization is robust to the arrival of additional buyers in the second period. The optimal mechanism is fully characterized for linear demand, with priority pricing being optimal if agents are sufficiently patient.

The design of tubular joints with slender cross-sections is currently limited by the validity ranges of established international design standards. Aiming to assess the structural behaviour of tubular joints characterised by thin-walled chord cross-sections, this paper initially reports, an experimental investigation into tubular T-joints consisted of CHS braces welded to thin-walled cold-formed RHS chords, which slenderness values were outside of the current design standard limits. The experimental programme was carried out on 12 cold-formed steel slender cross-section prototypes where the braces were subjected to axial compressive loading. The geometric parameters, including chord and brace thickness and brace diameter were varied. The connected chord face failure was the failure mode observed in all tests. The results of the experimental tests were thoroughly discussed. A second step was used to calibrate a numerical model that was the basis for a parametric analysis involving the most relevant parameters affecting the joint's behaviour. The obtained joint's strengths were compared with those forecasted by ISO 14346 developed for compact cross-sections modifying the chord stress function concerning the elastic cross-section modulus and effective cross-section area when slender cross-section chords are concerned. However, this approach leads to scattered predictions, roughly too conservative. Finally, this paper proposes an alternative design approach for the studied joints that are more accurate in predicting their strength when compared to the presented experimental and numerical results.

BACKGROUND: There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term. METHODS: Observational case series and case-control studies reporting 33 cases of recurrent, symptomatic, qRT-PCR positive COVID-19. Recurrent disease was defined as symptomatic recurrence after symptom-free clinical recovery, with release from isolation >14 days from the beginning of symptoms confirmed by qRT-PCR. The case control study-design compared this group of patients with a control group of 62 patients randomly selected from the same COVID-19 database. RESULTS: Of 33 recurrent COVID-19 patients, 26 were female and 30 were HCW. Mean time to recurrence was 50.5 days which was associated with being a HCW (OR 36.4 (p

The genus Cnidoscolus (Euphorbiaceae) is widely distributed in tropical areas. In the Northeast of Brazil, the species C. quercifolius is endemic and has been used in traditional medicine. In this study, a novel protein was isolated from C. quercifolius seeds and characterized by its molecular weight, primary structure, isoelectric point (pI), and carbohydrate content. The hypoglycemic activity of this protein was investigated by in vitro assay with the RIN-5F glucose-responsive cell line and in vivo test using alloxan-induced diabetic mice models. In addition, safe use of the protein was also investigated by cytotoxicity, hemagglutinating, and immunogenicity assays. The protein which was named Cq-IMP (Cnidoscolus quercifolius - Insulin Mimetic Protein) showed a single 11.18 KDa glycopolypeptide chain (16.4% of carbohydrates, m/m), pI of 8.0 and N-terminal sequence (TKDPELKQcKKQQKKqQQYDDDDKK) with similarity around 46-62% to sucrose binding protein-like and vicilin-like protein that was confirmed by mass spectrometry tryptic peptides analysis. Besides that, Cq-IMP presented anti-insulin antibody cross-reactivity as hypoglycemic activity in both in vitro and in vivo models. Additionally, it did not present any toxicity by methods tested. In conclusion, Cq-IMP is an insulin-mimetic protein, with a potent hypoglycemic activity and no toxicity showing great potential for therapeutic applications and drug development.

Dermatophytes belonging to Trichophyton ssp. are important anthropophilic and zoophilic pathogens, which developed resistance to griseofulvin, the common antifungal drug used to treat dermatophytosis. In this context, Moringa oleifera seed proteins have been described as antifungal agents with potential applications. Thus, this work aimed to evaluate the antidermatophytic in vitro, focusing on mechanisms, and in vivo potential of Mo-CBP4, purified from M. oleifera seeds. Mo-CBP4was purified after protein extraction with 50 mM Tris-HCl buffer, pH 8.0, and chromatography on chitin and CM Sepharose™ columns and antidermatophytic potential of Mo-CBP4 evaluated in vitro and in vivo. In vitro, Mo-CBP4 reduced in 50% the germination of microconidia of Trichophyton mentagrophytes at 45 μM; but did not show inhibition of mycelial growth. Mo-CBP4 (45 μM) presents the inhibitory activity even when incubated with N-acetyl- d -glucosamine (NAG). Analysis of the mechanisms of Mo-CBP4 revealed an increase in membrane permeability, ROS overproduction and damage to cell wall leading to microconidia death. Furthermore, using in vivo models, Mo-CBP4 (5, 10 and 20 mg g−1) reduced the severity and time of dermatophytosis. Altogether, these findings indicate that Mo-CBP4 has great potential for the development of novel antifungal drugs for the clinical treatment of dermatophytosis.

In mechanism design problems where the outside option is a game, a version of the intuitive criterion restricts beliefs formed off-path in case of disagreement, and thus credible punishments for rejecting to participate. However, for virtual implementation, participation constraints can be relaxed by “designing” beliefs following disagreement using self-rejections: with a small probability that depends on the reported type profile, a mediator rejects the agreement in a way that is indistinguishable from rejection by an agent. Participation constraints can be further relaxed if the mediator makes private recommendations before the outside game is played. Any punishment (by all players except the rejector) such that each player-type is never asked to use an action he does not use in any Bayesian solution of the outside game is a credible punishment.

This dataset is related to the article "Insight Into the Long Noncoding RNA and mRNA Coexpression Profile in the Human Blood Transcriptome Upon Leishmania infantum Infection" by S.R. Maruyama, C.A. Fuzo, A.E.R. Oliveira, L.A. Rogerio, N.T. Takamiya, G. Pessenda, E.V. de Melo, A.M. da Silva, A.R. Jesus, V. Carregaro, H.I. Nakaya, R.P. Almeida and J.S. da Silva. Frontiers in Immunology, 2022. Through the reuse of raw sequencing data, we generated original dataset by performing a dual RNA-seq mapping procedure to survey the parasite transcripts found in RNA-seq samples from blood of visceral leishmaniasis patients. Diseased patients with active infection displayed the highest number of reads mapped to

A series of Pd/Al2O3 catalysts coated with N-isopropylacrylamide polymer (p-NIPAM) brushes with increasing particle size of the support were prepared to study the interplay between mass transport limitations and the ability of the thermo-responsive catalysts to modify reactivity during reaction. Nitrite hydrogenation in water was chosen as probe reaction, which is a key step in the reduction of nitrites and nitrates from drinking water. The results show that the apparent activation energy decreases on increasing temperature above the LCST, i.e. the temperature where the polymer undergoes a phase change, for catalyst with particle sizes between 38 and 100 μm, alluding to a significant increase in mass transfer limitations. In sharp contrast, both p-NIPAM modified catalysts with smaller particle size and uncoated catalysts do not show this change in activation energy with temperature. Detailed multi-physics mass transport and reaction modelling indicated that the transport of the limiting reagent, hydrogen in this case, is severely reduced when the p-NIPAM collapses at temperatures above its LCST. It is concluded that effective reaction control using stimulus responsive polymers requires the system to be close to the mass transport limitation regime, to maximize the effect of the conformation change of the polymer on the catalyst performance and achieve sharp and reversible transitions from active to inactive.

Plant proteins are emerging as an alternative to conventional treatments against candidiasis. The aim of this study was to better understand the mechanism of action of Mo-CBP2 against Candida spp, evaluating redox system activity, lipid peroxidation, DNA degradation, cytochrome c release, medium acidification, and membrane interaction. Anti-candida activity of Mo-CBP2 decreased in the presence of ergosterol, which was not observed with antioxidant agents. C. albicans treated with Mo-CBP2 also had catalase and peroxidase activities inhibited, while superoxide dismutase was increased. Mo-CBP2 increased the lipid peroxidation, but it did not alter the ergosterol profile in live cells. External medium acidification was strongly inhibited, and cytochrome c release and DNA degradation were detected. Mo-CBP2 interacts with cell membrane constituents, changes redox system enzymes in C. albicans and causes lipid peroxidation by ROS overproduction. DNA degradation and cytochrome c release suggest apoptotic or DNAse activity. Lipid peroxidation and H+-ATPases inhibition may induce the process of apoptosis. Finally, Mo-CBP2 did not have a cytotoxic effect in mammalian Vero cells. This study highlights the biotechnological potential of Mo-CBP2 as a promising molecule with low toxicity and potent activity. Further studies should be performed to better understand its mode of action and toxicity.

We describe a globally rare example of a tetrapod burrow from the Upper Cretaceous Bauru Group (Bauru Basin) from Peirópolis, Minas Gerais State, Brazil. The sedimentary succession containing the burrow includes a rich vertebrate assemblage comprising fish, podocnemid turtles, mesoeucrocodylians, saurischian dinosaurs, among others. The burrow is composed of an oblique tunnel (~30°), oval in cross-section, with a horizontal and sub-oval terminal chamber; it is 1.3 m long from the midpoint of its inferred entrance to the midpoint of the bottom of the chamber. It occurs in the upper portion of a sandstone succession, interpreted as a braided channel deposit, and the burrow-fill comprises medium-grained sandstone with mudstone intraclasts derived from fluvial floodplain facies. it is overlain by other fluvial channel deposits. Analyses suggest that the burrow was dug after the filling of the braided channel and during the pedogenesis of its exposed upper surface. Based on burrow morphology and size, the most plausible producer of this burrow is a notosuchian mesoeucrocodylian, such as small to mid-sized notosuchians (e.g., sphagesaurids). The Bauru Group has an extensive fossil record of notosuchians with disparate morphologies, and it is noteworthy that the small-sized notosuchian Labidiosuchus amicum comes from the same unit as the burrow. Moreover, arid to semi-arid conditions have been inferred for fossil-bearing rocks of this unit, and as such the data here presented add to our palaeoecological knowledge of Cretaceous mesoeucrocodylians in Gondwana. Moreover, it constitutes a new Cretaceous record of a tetrapod burrow during a period when such ichnofossils are globally rare. Fil: Martinelli, Agustín Guillermo. Universidade Federal Do Triangulo Mineiro; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina Fil: Basilici, Giorgio. Universidade Estadual de Campinas; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; Argentina Fil: Fiorelli, Lucas Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; Argentina Fil: Klock, Carolina. Universidade Federal de Ouro Preto; Brasil. Universidade Federal de Minas Gerais; Brasil Fil: Karfunkel, Joachim. Universidade Federal de Minas Gerais; Brasil Fil: Diniz, Ariela Costa. Universidade Federal de Minas Gerais; Brasil Fil: Soares, Marcus V. T.. Universidade Estadual de Campinas; Brasil Fil: Marconato, André. Universidade Federal de Ouro Preto; Brasil Fil: da Silva, João Ismael. Fundação Cultural de Uberaba; Brasil. Universidade Federal Do Triangulo Mineiro; Brasil Fil: Ribeiro, Luiz Carlos B.. Universidade Federal Do Triangulo Mineiro; Brasil Fil: Marinho, Thiago S.. Universidade Federal Do Triangulo Mineiro; Brasil

Human activities have enhanced environmental contamination by heavy metals such as mercury. One of the possible approaches to reducing mercury toxicity is chelation, with several plant compounds demonstrating this effect, such as gallic acid. The objective of this study was to evaluate the antioxidant, metal chelating and cytoprotective activity of gallic acid against the action of Mercury Chloride (HgCl2). Iron II and III chelation as well as antioxidant activity assays were performed using the DPPH (1,1-Diphenyl-1-picrylhydrazyl) method. The interaction between the metal and the phenolic compound was identified by infrared spectroscopy. The Minimum Inhibitory Concentration (MIC) was determined by microdilution. From these results, and using a sub-inhibitory concentration (64 μg mL−1 for bacterial and fungal assay respectively) of the phenolic compound, the Minimum Bactericidal (MBC) and Minimum Fungicide Concentration (MFC) were evaluated. Allelopathy and cytoprotection assays were performed using eukaryotic and prokaryotic models, with a protection of the fungi being observed. When using a plant model with a sub-allelopathic concentration (32 μg mL−1), the results demonstrated the cytoprotective effect of gallic acid against HgCl2, increasing the extension of caulicles and radicles as well as their dry mass. This protection may be associated with the chelating effect of gallic acid. These results demonstrate that natural products such as gallic acid may be used for toxic metal chelation allowing plant development in polluted environments thus retrieving land usage for crops or forestry initiatives.

In this survey we establish geometric C 1 + α regularity estimates for bounded solutions of a number of nonlinear evolution models in divergence and non-divergence form. The main insights to obtain such estimates are based on geometric tangential methods, and make use of systematic oscillation mechanisms combined with intrinsic scaling techniques.

The aim of this study was to evaluate the caffeic acid antioxidant and cytoprotective activity against Mercury Chloride (HgCl2) action. DPPH and iron chelation assays were performed to evaluate the antioxidant activity. The interaction between the metal and phenolic compounds was identified by Fourier-transform infrared spectroscopy (FTIR) and microbiological tests were performed using microdilution, obtaining the Minimum Inhibitory Concentration (MIC), the Minimum Bactericidal Concentration (MBC) and the Minimum Fungicidal Concentration (MFC). To evaluate cytoprotection in the plant model, a sub-allelopathic product concentration (32 μg/mL) and different heavy metal concentrations were used. Caffeic acid was observed to confer cytoprotection to Lactuca sativa seeds, allowing greater growth and development of both plant radicles and caulicles. This result may be attributed to the chelating and antioxidant effect of the caffeic acid, thereby reducing the toxicity of the metal. These results demonstrate the possibility of using natural products as an alternative for heavy metal chelation and to enable a greater development of plants present in contaminated areas. These results become important given the high environmental contamination by heavy metals recently, preventing the growth of important plants both from an environmental and economic point of view, thus providing a viable alternative for minimizing the problem becomes indispensable.

In this work a new type of hybrid PI controller is presented using the Paraconsistent Logic (PL) as the basis for the mathematical and logical treatment of the signals corresponding to the control variables. This control has the conventional actions PI (Proportional and Integral) together with the logical actions structured in the concepts of Paraconsistent Logic. Compared to conventional techniques, this new type of Hybrid PI Controller with Paraconsistent Logic responded well to the various tests performed in the control loop. The tests and the technical validations were done with evidences that prove the efficiency of the paraconsistent concepts.

This pioneering study reports on the investigation of C-S-H in as-produced ternary cement pastes while highly reactive supplementary cementitious materials, such as silica fume (SF) and metakaolin (MK), and colloidal nanosilica (NS) are included into the mixtures. Several techniques are used to evaluate the microstructure of the pastes containing colloidal NS (3%), SF (10%) and MK (10%): Consistency, compressive strength, thermogravimetric analyses, Fourier transform infrared spectroscopy, scanning electron microscopy (with energy dispersive X-ray spectrometry), 29Si-nuclear magnetic resonance, and mercury intrusion porosimetry. Ternary mixtures containing SF or MK require the highest superplasticizer (SP) consumption of 1.55% and 1.92%, respectively. Impressively, in late stage of aging, i.e 28 and 91 days of hydration, ternary mixtures reach compressive strength respectively above 90 MPa and 100 MPa, meaning an increase of about 30% above of the compressive strength of the reference paste. Moreover, the ternary MK-based paste shows increase C-S-H production, decreasing Ca/Si ratio and superior increasing mean chain length (MCL) of about 11.1 while compared with the MCL of the reference paste (about 4.6). Likewise, the highest relative reduction in mean porous size (56%) and the lowest total, The authors would like to thank the Furnas Centrais Elétricas, Chemistry Institute from Federal University of Goiás, State University of Goiás and Unievangélica Center of Anápolis, Postgraduate Program in Structural Engineering and Construction from University of Brasília, Brazil Geology Institute from University of Brasília, Geochronology Laboratory from University of Brasília, Addendum to the Framework Agreement for Collaboration between University of Brasilia (UnB-Brazil) and Spanish National Research Council, Spain (CSIC-Spain) (ref: 201504001653451013W-2017), Eduardo Torroja Institute for Construction Science.