Gas tungsten arc welding of as-cast AlCoCrFeNi2.1 eutectic high entropy alloy

Funding Information: JS, JGL and JPO acknowledge Fundação para a Ciência e a Tecnologia (FCT - MCTES) for its financial support via the project UID/00667/2020 (UNIDEMI). JPO acknowledges the funding by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication – i3N. JS acknowledges the China Scholarship Council for funding the Ph.D. grant (CSC NO. 201808320394). JGL acknowledges FCT – MCTES for funding the Ph.D. grant 2020.07350.BD. TAR acknowledges FCT – MCTES for funding the Ph.D. grant SFRH/BD/144202/2019. Publisher Copyright: © 2022 The AuthorsThe AlCoCrFeNi2.1 eutectic high entropy alloy is of great interest due to its unique mechanical properties combining both high strength and plasticity. Here, gas tungsten arc welding was performed for the first time on an as-cast AlCoCrFeNi2.1 alloy. The microstructural evolution of the welded joints was assessed by combining electron microscopy with electron backscatter diffraction, synchrotron X-ray diffraction analysis and thermodynamic calculations. Microhardness mapping and tensile testing coupled with digital image correlation were used to investigate the strength distribution across the joint. The base material, heat affected zone and fusion zone are composed of an FCC + B2 BCC eutectic structure, although the relative volume fractions vary across the joint owing to the weld thermal cycle. The BCC nanoprecipitates that existed in the base material started to dissolve into the matrix in the heat affected zone and closer to the fusion zone boundary. Compared to the as-cast base material, the fusion zone evidenced grain refinement owing to the higher cooling rate experienced during solidification. This translates into an increased hardness in this region. The joints exhibit good strength/ductility balance with failure occurring in the base material. This work establishes the potential for using arc-based welding for joining eutectic high entropy alloys.publishersversionpublishe

Microstructure evolution and mechanical properties in a gas tungsten arc welded Fe42Mn28Co10Cr15Si5 metastable high entropy alloy

Funding Information: JS, JGL and JPO acknowledge Fundação para a Ciência e a Tecnologia (FCT - MCTES) for its financial support via the project UID/00667/2020 (UNIDEMI). JPO acknowledges funding by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P. in the scope of the projects LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication – i3N. JS acknowledges the China Scholarship Council for funding the Ph.D. grant (CSC NO. 201808320394). JGL acknowledges FCT – MCTES for funding the Ph.D. grant 2020.07350.BD. TAR acknowledges FCT – MCTES for funding the Ph.D. grant SFRH/BD/144202/2019. The authors acknowledge DESY (Hamburg, Germany), a member of the Helmholtz Association HGF, for the provision of experimental facilities. Beamtime was allocated for proposal I-20220492 EC. The research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. Funding Information: JS, JGL and JPO acknowledge Fundação para a Ciência e a Tecnologia (FCT - MCTES) for its financial support via the project UID/00667/2020 (UNIDEMI). JPO acknowledges funding by national funds from FCT - Fundação para a Ciência e a Tecnologia , I.P., in the scope of the projects LA/P/0037/2020 , UIDP/50025/2020 and UIDB/50025/2020 of the Associate Laboratory Institute of Nanostructures, Nanomodelling and Nanofabrication – i3N. JS acknowledges the China Scholarship Council for funding the Ph.D. grant (CSC NO. 201808320394 ). JGL acknowledges FCT – MCTES for funding the Ph.D. grant 2020.07350 .BD. TAR acknowledges FCT – MCTES for funding the Ph.D. grant SFRH/BD/144202/2019 . The authors acknowledge DESY (Hamburg, Germany), a member of the Helmholtz Association HGF , for the provision of experimental facilities. Beamtime was allocated for proposal I-20220492 EC. The research leading to this result has been supported by the project CALIPSOplus under the Grant Agreement 730872 from the EU Framework Programme for Research and Innovation HORIZON 2020. Publisher Copyright: © 2023 The AuthorsWeldability studies on high entropy alloys are still relatively scarce, delaying the deployment of these materials into real-life applications. Thus, there is an urgent need for in-depth studies of the weldability of these novel advanced engineering alloys. In the current work, an as-cast Fe42Mn28Co10Cr15Si5 metastable high entropy alloy was welded for the first time using gas tungsten arc welding. The weld thermal cycle effect on the microstructure evolution over the welded joint was examined using electron microscopy in combination with electron backscatter diffraction, synchrotron X-ray diffraction analysis, and thermodynamic calculations. Furthermore, tensile testing and hardness mapping were correlated with the microstructure evolution. The microstructure evolution across the joint is unveiled, including the origin of the ε-h.c.p. phase at different locations of the material. Different strengthening effects measured throughout the joint are associated with the weld thermal cycle and resulting microstructure. A synergistic effect of smaller grain size of the ε-h.c.p. phase in the fusion zone, overturns the reduced volume fraction of this phase, increasing the local strength of the material. Moreover, the brittle nanosized σ phase was also found to play a critical role in the joints’ premature failure during mechanical testing.publishersversionpublishe

LOSITAN: A workbench to detect molecular adaptation based on a Fst-outlier method

<p>Abstract</p> <p>Background</p> <p>Testing for selection is becoming one of the most important steps in the analysis of multilocus population genetics data sets. Existing applications are difficult to use, leaving many non-trivial, error-prone tasks to the user.</p> <p>Results</p> <p>Here we present LOSITAN, a selection detection workbench based on a well evaluated <it>F</it>_<it>st</it>-outlier detection method. LOSITAN greatly facilitates correct approximation of model parameters (e.g., genome-wide average, neutral <it>F</it>_<it>st</it>), provides data import and export functions, iterative contour smoothing and generation of graphics in a easy to use graphical user interface. LOSITAN is able to use modern multi-core processor architectures by locally parallelizing fdist, reducing computation time by half in current dual core machines and with almost linear performance gains in machines with more cores.</p> <p>Conclusion</p> <p>LOSITAN makes selection detection feasible to a much wider range of users, even for large population genomic datasets, by both providing an easy to use interface and essential functionality to complete the whole selection detection process.</p

Biomedical potential of fucoidan, a seaweed sulfated polysaccharide: from a anticancer agent to a building block of cell encapsulating systems for regenerative medicine

Marine macroalgae or seaweeds synthesize a wide variety of polymers and smaller compounds with several bioactivities, among which the sulfated polysaccharides acquire greater relevance not only due to the reported antioxidant, antiviral and anticancer[1] activities, but also to the resemblance of extracellular matrix glycosaminoglycans found in the human body[2]. In this study, the potential of fucoidan (Fu) isolated from brown seaweed Fucus vesiculosus for therapeutical use has been evaluated, focusing in its performance as antitumoral agent (bioactive role) or as building block of cell encapsulating systems (structural role). Materials and Methods: The anticancer activity of Fu extracts was assessed by evaluating the cytotoxic behavior over two human breast cancer cell lines (MCF-7 and MDA-MB-231) in in-vitro culture, using human fibroblasts and endothelial cells (HPMEC-ST1 and MRC-5, respectively) as reference. Regarding the structural role, Fu was modified by methacrylation reaction (MFu) using methacrylic acid and further crosslinked using visible radiation and triethanolamine and eosin-y as photoinitiators. The photocrosslinking was performed on MFu solution droplets placed in a silica-based superhydrophobic surface[3], allowing the formation of particles[4] (since natural Fu is highly soluble in water and ion gelation is not effective). Biological performance of the developed particles was assessed by in vitro culture of fibroblasts and pancreatic cells (L929 and 1.1B4, respectively) in contact with MFu particles, up to 7 days. The ability of the developed materials to support adhesion and proliferation of cells was evaluated for both types of cells. Results and Discussion: The tested anticancer activity is not ubiquitous on Fu extracts, being dependent on its chemical features, with molecular weight (Mw) representing a particular role. Specifically, Mw values around 60 kDa exhibited cytotoxic effects to human breast cancer cell lines, while not affecting normal fibroblasts or endothelial cells (which represent the cells of the healthy tissue that would be closer to the tumor in a real situation). A concentration range of 0.2 to 0.3 mg mL-1 from the selected Fu extract could be considered as the therapeutic window for further studies. Regarding fucoidanâ s role on innovative biomaterials, the developed MFu particles could support the proliferation of fibroblasts (L929), but also of human pancreatic beta cells (1.1B4), which tend to form pseudo-islets after 7 days in culture (Fig. 1). This pancreatic cells could be also successfully encapsulated, opening a new route for a diabetes mellitus type 1 therapeutic approach. Fig. 1: Confocal microscopy images of 1.1B4 cells cultured in the presence of fucoidan-based particles and organized in pseudo-islets (red â actin; blue â nuclei). Conclusion: The present work establishes fucoidan as a high performance building block for the development of advanced therapies for cancer (targeted therapy) or tissue and organ regeneration. It shed light on the relation between chemical structure and biological activity towards anti-cancer effect and proposes novel beta cell laden particles as injectable insulin producing systems to tackle diabetes.Funding from projects 0687_NOVOMAR_1_P (co-funded by INTERREG 2007-2013 / POCTEP), CarbPol_u_Algae (EXPL/MAR-BIO/0165/2013, funded by the Portuguese Foundation for Science and Technology, FCT), POLARIS (FP7-REGPOT-CT2012-316331) and ComplexiTE (ERC-2012-ADG 20120216-321266), funded by the European Union’s Seventh Framework Programme for Research and Development is acknowledged. ASF, SSS, NMO and DSC are also thankful to FCT for their individual fellowships

Dairy products and total calcium intake at 13 years of age and its association with obesity at 21 years of age

Background/objectives: Dairy products and specifically calcium have been suggested to play a role in obesity development but more longitudinal evidence is still needed. The objective of this study was to assess the association between dairy products and total calcium intake at age 13 and body mass index at age 21. Subjects/methods: This longitudinal study included 2159 individuals from the Epidemiological Health Investigation of Teenagers cohort (EPITeen), Porto, Portugal, evaluated at ages 13 and 21. Assessment consisted of anthropometrics measurements and structured questionnaires namely a semi-quantitative food frequency questionnaire to appraise food consumption in the past 12 months. Linear regression models were run in 941 individuals with complete information of confounders: gender, follow-up period, parents’ education, physical activity, energy, and total calcium intake. Results: Negative association was found on total calcium intake at age 13 with BMI at age 21 (model 0: β = −0.059 (95% CI: −0.113, −0.004) and model 1: −0.057 (95% CI: −0.113, −0.002)), however, no statistically significant association was found when adjusting for energy intake (model 2: β = −0.031 (95% CI: −0.110, 0.047). There were no associations between milk, yogurt, and cheese consumption at age 13 and BMI at age 21 when adjusting for confounders. Conclusions: This study did not support an independent effect of dairy products or total calcium intake in adolescence on later early adulthood adiposity.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) (POCI-01-0145-FEDER-016829), under the project MetHyOS (Ref. FCT PTDC/DTP-EPI/6506/2014) and the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). Also this study was developed with the support of the research teams of the Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine of Porto University; the EPIUnit—Public Health Institute of Porto University; and the EPITeen Cohort Study

A complex scenario of tuberculosis transmission is revealed through genetic and epidemiological surveys in Porto

Tuberculosis (TB) incidence is decreasing worldwide and eradication is becoming plausible. In low-incidence countries, intervention on migrant populations is considered one of the most important strategies for elimination. However, such measures are inappropriate in European areas where TB is largely endemic, such as Porto in Portugal. We aim to understand transmission chains in Porto through a genetic characterization of Mycobacterium tuberculosis strains and through a detailed epidemiological evaluation of cases.This work was developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and supported by contributions from Iceland, Liechtenstein and Norway through the European Economic Area Grants under the Public Health Initiative programme, (PT06, Project 000138DT1). TR is supported by the Portuguese Foundation for Science and Technology (FCT) through a post-doctoral grant (SFRH/BPD/108126/2015)info:eu-repo/semantics/publishedVersio

[Ru(bpy)2(NO)SO3](PF6), a Nitric Oxide Donating Ruthenium Complex, Reduces Gout Arthritis in Mice

Monosodium urate crystals (MSU) deposition induces articular inflammation known as gout. This disease is characterized by intense articular inflammation and pain by mechanisms involving the activation of the transcription factor NFκB and inflammasome resulting in the production of cytokines and oxidative stress. Despite evidence that MSU induces iNOS expression, there is no evidence on the effect of nitric oxide (NO) donors in gout. Thus, the present study evaluated the effect of the ruthenium complex donor of NO {[Ru(bpy)2(NO)SO3](PF6)} (complex I) in gout arthritis. Complex I inhibited in a dose-dependent manner MSU-induced hypersensitivity to mechanical stimulation, edema and leukocyte recruitment. These effects were corroborated by a decrease of histological inflammation score and recruitment of Lysm-eGFP+ cells. Mechanistically, complex I inhibited MSU-induced mechanical hypersensitivity and joint edema by triggering the cGMP/PKG/ATP-sensitive K (+) channels signaling pathway. Complex I inhibited MSU-induced oxidative stress and pro-inflammatory cytokine production in the knee joint. These data were supported by the observation that complex I inhibited MSU-induced NFκB activation, and IL-1β expression and production. Complex I also inhibited MSU-induced activation of pro-IL-1β processing. Concluding, the present data, to our knowledge, is the first evidence that a NO donating ruthenium complex inhibits MSU-induced articular inflammation and pain. Further, complex I targets the main physiopathological mechanisms of gout arthritis. Therefore, it is envisaged that complex I and other NO donors have therapeutic potential that deserves further investigation

ALDH1A2 (RALDH2) genetic variation in human congenital heart disease

Abstract\ud \ud \ud \ud Background\ud \ud Signaling by the vitamin A-derived morphogen retinoic acid (RA) is required at multiple steps of cardiac development. Since conversion of retinaldehyde to RA by retinaldehyde dehydrogenase type II (ALDH1A2, a.k.a RALDH2) is critical for cardiac development, we screened patients with congenital heart disease (CHDs) for genetic variation at the ALDH1A2 locus.\ud \ud \ud \ud Methods\ud \ud One-hundred and thirty-three CHD patients were screened for genetic variation at the ALDH1A2 locus through bi-directional sequencing. In addition, six SNPs (rs2704188, rs1441815, rs3784259, rs1530293, rs1899430) at the same locus were studied using a TDT-based association approach in 101 CHD trios. Observed mutations were modeled through molecular mechanics (MM) simulations using the AMBER 9 package, Sander and Pmemd programs. Sequence conservation of observed mutations was evaluated through phylogenetic tree construction from ungapped alignments containing ALDH8 s, ALDH1Ls, ALDH1 s and ALDH2 s. Trees were generated by the Neighbor Joining method. Variations potentially affecting splicing mechanisms were cloned and functional assays were designed to test splicing alterations using the pSPL3 splicing assay.\ud \ud \ud \ud Results\ud \ud We describe in Tetralogy of Fallot (TOF) the mutations Ala151Ser and Ile157Thr that change non-polar to polar residues at exon 4. Exon 4 encodes part of the highly-conserved tetramerization domain, a structural motif required for ALDH oligomerization. Molecular mechanics simulation studies of the two mutations indicate that they hinder tetramerization. We determined that the SNP rs16939660, previously associated with spina bifida and observed in patients with TOF, does not affect splicing. Moreover, association studies performed with classical models and with the transmission disequilibrium test (TDT) design using single marker genotype, or haplotype information do not show differences between cases and controls.\ud \ud \ud \ud Conclusion\ud \ud In summary, our screen indicates that ALDH1A2 genetic variation is present in TOF patients, suggesting a possible causal role for this gene in rare cases of human CHD, but does not support the hypothesis that variation at the ALDH1A2 locus is a significant modifier of the risk for CHD in humans.Work supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 01/000090; 00/030722; 01/142381; 02/113402; 03/099982; 04/116068; 04/157044 and Conselho Nacional de Desenvolvimento Científico e Tecnológico 481872/20078. We would like to thank the careful work and thoughtful suggestions of the two reviewers responsible for the reviewing editorial process.Work supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 01/00009-0; 00/03072-2; 01/14238-1; 02/11340-2; 03/09998-2; 04/11606-8; 04/15704-4 and Conselho Nacional de Desenvolvimento Científico e Tecnológico 481872/2007-8. We would like to thank the careful work and thoughtful suggestions of the two reviewers responsible for the reviewing editorial process

A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells

<p>Abstract</p> <p>Background</p> <p>Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd₂[<it>S_(-)</it>C², N-dmpa]₂(μ-dppe)Cl₂} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies.</p> <p>Methods</p> <p>B16F10-Nex2 cells were treated <it>in vitro </it>with C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treated <it>in vitro </it>with C7a.</p> <p>Results</p> <p>Cyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineages <it>in vitro</it>, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells.</p> <p>Conclusions</p> <p>The cyclopalladated C7a complex is an effective chemotherapeutic anticancer compound against primary and metastatic murine and human tumors, including cisplatin-resistant cells, inducing apoptotic cell death via the intrinsic pathway.</p