Smelting and recycling evidences from the Late Bronze Age habitat site of Baiões (Viseu, Portugal)

Many aspects of bronze production during Late Bronze Age in Western Europe are so far unknown. In the present study selected artefact fragments and metallurgical debris, which include a slag fragment, from the emblematic Late Bronze Age habitat site of Castro da Senhora da Guia de Baio˜es (Viseu, Portugal) have been studied by optical microscopy, micro-EDXRF, SEM–EDS and XRD. Evidences were found for bronze production involving smelting and recycling. Compositional analysis showed that the artefacts are made of a bronze with 133 wt.% Sn (average and one standard deviation) and a low impurity pattern, namely <0.1 wt.% Pb, being comparable with the composition of other bronzes from the same region (the Central Portuguese Beiras). This alloy is generally different from elsewhere Atlantic and Mediterranean bronzes, which show frequently slightly lower Sn contents and higher impurity patterns,namely Pb which is often present as an alloying element. The present study gives further support to early proposals suggesting the exploration of the Western Iberian tin resources during Late Bronze Age, and besides that, it indicates that metalworking and smelting could have been a commonplace activity requiring no specific facilities, being bronze produced at a domestic scale in this Western extreme of Europe

Synthesis and characterization of Locust Bean Gum derivatives and their application in the production of nanoparticles

The development of LBG-based nanoparticles intending an application in oral immunization is presented. Nanoparticle production occurred by mild polyelectrolyte complexation, requiring the chemical modification of LBG. Three LBG derivatives were synthesized, namely a positively charged ammonium derivative (LBGA) and negatively charged sulfate (LBGS) and carboxylate (LBGC) derivatives. These were characterized by Fourier-transform infrared spectroscopy, elemental analysis, nuclear magnetic resonance spectroscopy, gel permeation chromatography, and x-ray diffraction. As a pharmaceutical application was aimed, a toxicological analysis of the derivatives was performed by both MTT test and LDH release assay. Several nanoparticle formulations were produced using LBGA or chitosan (CS) as positively charged polymers, and LBGC or LBGS as negatively charged counterparts, producing nanoparticles with adequate properties regarding an application in oral immunization.info:eu-repo/semantics/publishedVersio

An economic and greenhouse gas footprint assessment of international maritime transportation of hydrogen using liquid organic hydrogen carriers

The supply, storage, and (international) transport of green hydrogen (H2) are essential for the decarbonization of the energy sector. The goal of this study was to assess the final cost-price and carbon footprint of imported green H2 in the market via maritime shipping of liquid organic hydrogen carriers (LOHCs), including dibenzyl toluene-perhydro-dibenzyltoluene (DBT-PDBT) and toluene-methylcyclohexane (TOL-MCH) systems. The study focused on logistic steps in intra-European supply chains in different scenarios of future production in Portugal and demand in the Netherlands and carbon tariffs between 2030 and 2050. The case study is based on a formally accepted agreement between Portugal and the Netherlands within the Strategic Forum on Important Projects of Common European Interest (IPCEI). Under the following assumptions, the results show that LOHCs are a viable technical-economic solution, with logistics costs from 2030 to 2050 varying between 0.30 and 0.37 €/kg-H2 for DBT-PDBT and 0.28–0.34 €/kg-H2 for TOL-MCH. The associated CO2 emissions of these international H2 supply chains are between 0.46 and 2.46 kg-CO2/GJ (LHV) and 0.55–2.95 kg-CO2/GJ (LHV) for DBT-PDBT and TOL-MCH, respectively

Multimethod Assessment of Design, Metallurgical, and Mechanical Characteristics of Original and Counterfeit ProGlider Instruments

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.A multimethod study was conducted to assess the differences between original (PG-OR) and counterfeit (PG-CF) ProGlider instruments regarding design, metallurgical features, and mechanical performance. Seventy PG-OR and PG-CF instruments (n = 35 per group) were evaluated regarding the number of spirals, helical angles, and measuring line position by stereomicroscopy, while blade symmetry, cross-section geometry, tip design, and surface were assessed by scanning electron microscopy. Energy-dispersive X-ray spectroscopy and differential scanning calorimetry were used to identify element ratio and phase transformation temperatures, while cyclic fatigue, torsional, and bending testing were employed to assess their mechanical performance. An unpaired t-test and nonparametric Mann–Whitney U test were used to compare instruments at a significance level of 5%. Similarities were observed in the number of spirals, helical angles, blade symmetry, cross-sectional geometries, and nickel–titanium ratios. Measuring lines were more reliable in the original instrument, while differences were noted in the geometry of the tips (sharper tip for the original and rounded for the counterfeit) and surface finishing with PG-CF presenting more surface irregularities. PG-OR showed significantly more time to fracture (118 s), a higher angle of rotation (440°), and a lower maximum bending load (146.3 gf) (p 0.05). Although the tested instruments had a similar design, the original ProGlider showed superior mechanical behavior. The results of counterfeit ProGlider instruments were unreliable and can be considered unsafe for glide path procedures.publishersversionpublishe

Establishment and characterization of human pluripotent stem cells-derived brain organoids to model cerebellar diseases

Supplementary Information Te online version contains supplementary material available at https://doi.org/ 10.1038/s41598-022-16369-y.The establishment of robust human brain organoids to model cerebellar diseases is essential to study new therapeutic strategies for cerebellum-associated disorders. Machado-Joseph disease (MJD) is a cerebellar hereditary neurodegenerative disease, without therapeutic options able to prevent the disease progression. In the present work, control and MJD induced-pluripotent stem cells were used to establish human brain organoids. These organoids were characterized regarding brain development, cell type composition, and MJD-associated neuropathology markers, to evaluate their value for cerebellar diseases modeling. Our data indicate that the organoids recapitulated, to some extent, aspects of brain development, such as astroglia emerging after neurons and the presence of ventricular-like zones surrounded by glia and neurons that are found only in primate brains. Moreover, the brain organoids presented markers of neural progenitors proliferation, neuronal differentiation, inhibitory and excitatory synapses, and firing neurons. The established brain organoids also exhibited markers of cerebellar neurons progenitors and mature cerebellar neurons. Finally, MJD brain organoids showed higher ventricular-like zone numbers, an indication of lower maturation, and an increased number of ataxin-3-positive aggregates, compared with control organoids. Altogether, our data indicate that the established organoids recapitulate important characteristics of human brain development and exhibit cerebellar features, constituting a resourceful tool for testing therapeutic approaches for cerebellar diseases.This work was funded by the European Regional Development Fund (ERDF) through the Centro 2020 Regional Operational Programme under BrainHealth2020 projects (CENTRO-01-0145-FEDER-000008), through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, under projects — UIDB/04539/2020 and UIDP/04539/2020, POCI-01-0145-FEDER-030737 (NeuroStemForMJD, PTDC/BTM-ORG/30737/2017), CEEC-IND/04242/2017, PhD Scholarships 2020.04751.BD and 2020.07385.BD. It was also funded by the National Ataxia Foundation, the French Muscular Dystrophy Association (AFM-Téléthon) Trampoline Grant #20126, EU Joint Programme—Neurodegenerative Disease Research (JPND) Project JPCO FUND/0005/2015-ModelPolyQ), and the Richard Chin and Lily Lock Machado-Joseph Disease Research Fund.info:eu-repo/semantics/publishedVersio

The Egas Moniz histology digital platform : a dream that came true

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio

Exploring Research Priorities of Parents Who Have Children With Down Syndrome, Cleft Lip With or Without Cleft Palate, Congenital Heart Defects, and Spina Bifida Using ConnectEpeople:A Social Media Coproduction Research Study

Background: Using social media for research purposes is novel and challenging in terms of recruitment, participant knowledge about the research process, and ethical issues. This paper provides insight into the recruitment of European parents of children with specific congenital anomalies to engage in coproduction research by using social media. Secret Facebook groups, providing optimal security, were set up for newly recruited research-aware parents (RAPs) to communicate privately and confidentially with each other and for the research team to generate questions and to interpret findings. Objective: This study aimed to use social media for the recruitment and engagement of parents in research and to determine the research priorities of parents who have children with Down syndrome, cleft lip with or without cleft palate, congenital heart defects, and spina bifida. Methods: The design was exploratory and descriptive with 3 phases. Phase 1 included the recruitment of RAPs and generation of research questions important to them; phase 2 was a Web-based survey, designed using Qualtrics software, and phase 3 included analysis and ranking of the top 10 research questions using an adapted James Lind Alliance approach. Simple descriptive statistics were used for analysis, and ethical approval was obtained from the Ethics Filter Committee of the Institute of Nursing and Health Research, Ulster University. Results: The recruitment of 32 RAPs was a sensitive process, varying in the time taken to consent (mean 51 days). However, parents valued the screening approach using the State-Trait Anxiety Inventory as a measure to ensure their well-being (mean 32.5). In phase 1, RAPs generated 98 research questions. In phase 2, 251 respondents accessed the Web-based survey, 248 consented, and 80 completed the survey, giving a completeness rate of 32.3% (80/248). Most parents used social media (74/80, 92%). Social media, online forums, and meeting in person were ranked the most preferable methods for communication with support groups networks and charities. Most respondents stated that they had a good understanding of research reports (71/80, 89%) and statistics (68/80, 85%) and could differentiate among the different types of research methodologies (62/80, 78%). Phase 3 demonstrated consensus among RAPs and survey respondents, with a need to know the facts about their child's condition, future health, and psychosocial and educational outcomes for children with similar issues. Conclusions: Social media is a valuable facilitator in the coproduction of research between parents and researchers. From a theoretical perspective, ocularcentrism can be an applicable frame of reference for understanding how people favor visual contact.This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 733001.info:eu-repo/semantics/publishedVersio

Rabbit derived VL single-domains as promising scaffolds to generate antibody–drug conjugates

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.This work was supported by the Portuguese Funding Agency, Fundação para a Ciência e Tecnologia, FCT IP (SAICT/2017/32085, PTDC/QUI-OUT/3989/2021 and Ph.D. fellowship SFRH/BD/131468/2017 to ASA and SFRH/BD/90514/2012 to JD). CIISA has provided support through Project UIDB/00276/2020, funded by FCT and LA/P/0059/2020-AL4AnimalS. Research Institute for Medicines (iMed.ULisboa) acknowledges the financial support of Fundação para a Ciência e Tecnologia (Projects: PTDC/QUI-OUT/3989/2021; UIDB/04138/2020 and UIDP/04138/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).info:eu-repo/semantics/publishedVersio

Vitamin D-related polymorphisms and vitamin D levels as risk biomarkers of COVID-19 disease severity

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Vitamin D is a fundamental regulator of host defences by activating genes related to innate and adaptive immunity. Previous research shows a correlation between the levels of vitamin D in patients infected with SARS-CoV-2 and the degree of disease severity. This work investigates the impact of the genetic background related to vitamin D pathways on COVID-19 severity. For the first time, the Portuguese population was characterized regarding the prevalence of high impact variants in genes associated with the vitamin D pathways. This study enrolled 517 patients admitted to two tertiary Portuguese hospitals. The serum concentration of 25 (OH)D, was measured in the hospital at the time of patient admission. Genetic variants, 18 variants, in the genes AMDHD1, CYP2R1, CYP24A1, DHCR7, GC, SEC23A, and VDR were analysed. The results show that polymorphisms in the vitamin D binding protein encoded by the GC gene are related to the infection severity (p = 0.005). There is an association between vitamin D polygenic risk score and the serum concentration of 25 (OH)D (p = 0.04). There is an association between 25 (OH)D levels and the survival and fatal outcomes (p = 1.5e-4). The Portuguese population has a higher prevalence of the DHCR7 RS12785878 variant when compared with its prevalence in the European population (19% versus 10%). This study shows a genetic susceptibility for vitamin D deficiency that might explain higher severity degrees in COVID-19 patients. These results reinforce the relevance of personalized strategies in the context of viral diseases.This project was supported by the “Fundação para a Ciência e Tecnologia”, program “Research 4 Covid-19 Apoio especial a projetos de implementação rápida para soluções inovadoras de resposta à pandemia de COVID-19”. It was also partially supported by each institution.info:eu-repo/semantics/publishedVersio