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In this work, we present a novel application of the full-field energy-dispersive X-ray fluorescence (EDXRF) imaging system based on a MicroPattern Gaseous Detector (2D-THCOBRA) in the cultural heritage field. The detector has an intrinsic imaging capability with spatial resolution of 400μmFWHM, and is energy sensitive, presenting an energy resolution of approximately 1keVFWHM at 5.9keV. The full-field XRF scanner based on the 2D-THCOBRA detector allows mapping the distribution of elements in large area samples with high detection efficiency (75 % at 5.9keV), being a very promising choice for elemental mapping analysis of large area cultural heritage samples. In this work, we have demonstrated the imaging capabilities of the full-field XRF scanner and used it to assess the restoration of a Portuguese faience piece.

Ion beam analysis of fluorine has applications in research on teeth and bones, materials science, geochemistry and archaeometry. A novel PIGE (particle induced gamma-ray emission) standard free methodology for fluorine content determination for in-depth heterogeneous samples based on the excitation function of the 19F(p,p’$\gamma$)19F nuclear reaction is presented. New precise cross section measurements of this reaction in the proton energy range 2.1 to 4.1 MeV have been performed. In addition, the ERYA-Profiling code, a computer program specially developed for PIGE analysis of in-depth heterogeneous samples, employed this new excitation function in a case study where different fluorine simulated depth profiles probed the capability of insight into fluorine distributions in a given sample, showing the potential of PIGE analysis.

Nuclear Inst. and Methods in Physics Research, A, 1014 (2021) 165701. doi:10.1016/j.nima.2021.165701

Physics Letters B, 809 (2020) 135748. 10.1016/j.physletb.2020.135748

Siglec-15 is a conserved sialic acid-binding Ig-like lectin expressed on osteoclast progenitors that plays an important role in osteoclast development and function. It is also expressed by tumor-associated macrophages and by some tumors, where it is thought to contribute to the immunosuppressive microenvironment. It was shown previously that engagement of macrophage-expressed Siglec-15 with tumor cells expressing its ligand, sialyl Tn (sTn), triggered production of TGF-$\beta$. In the present study, we have further investigated the interaction between Siglec-15 and sTn on tumor cells and its functional consequences. Based on binding assays with lung and breast cancer cell lines and glycan-modified cells, we failed to see evidence for recognition of sTn by Siglec-15. However, using a microarray of diverse, structurally-defined glycans, we show that Siglec-15 binds with higher avidity to sialylated glycans other than sTn or related antigen sequences. In addition, we were unable to demonstrate enhanced TGF-$\beta$ secretion following co-culture of Siglec-15-expressing monocytic cells lines with tumor cells expressing sTn, or following Siglec-15 cross-linking with monoclonal antibodies. However, we did observe activation of the SYK/MAPK signaling pathway following antibody cross-linking of Siglec-15 that may modulate the functional activity of macrophages.

During the course of fungal infection, pathogen recognition by the innate immune system is critical to initiate efficient protective immune responses. The primary event that triggers immune responses is the binding of Pattern Recognition Receptors (PRRs), which are expressed at the surface of host immune cells, to Pathogen-Associated Molecular Patterns (PAMPs) located predominantly in the fungal cell wall. Most fungi have mannosylated PAMPs in their cell walls and these are recognized by a range of C-type lectin receptors (CTLs). However, the precise spatial distribution of the ligands that induce immune responses within the cell walls of fungi are not well defined. We used recombinant IgG Fc-CTLs fusions of three murine mannan detecting CTLs, including dectin-2, the mannose receptor (MR) carbohydrate recognition domains (CRDs) 4-7 (CRD4-7), and human DC-SIGN (hDC-SIGN) and of the $\beta$-1,3 glucan-binding lectin dectin-1 to map PRR ligands in the fungal cell wall of fungi grown in vitro in rich and minimal media. We show that epitopes of mannan-specific CTL receptors can be clustered or diffuse, superficial or buried in the inner cell wall. We demonstrate that PRR ligands do not correlate well with phylogenetic relationships between fungi, and that Fc-lectin binding discriminated between mannosides expressed on different cell morphologies of the same fungus. We also demonstrate CTL epitope differentiation during different phases of the growth cycle of Candida albicans and that MR and DC-SIGN labelled outer chain N-mannans whilst dectin-2 labelled core N-mannans displayed deeper in the cell wall. These immune receptor maps of fungal walls of in vitro grown cells therefore reveal remarkable spatial, temporal and chemical diversity, indicating that the triggering of immune recognition events originates from multiple physical origins at the fungal cell surface.

One of the trends in downstream processing comprises the use of ?anything-but-chromatography? methods to overcome the current downfalls of standard packed-bed chromatography. Precipitation and magnetic separation are two techniques already proven to accomplish protein purification from complex media, yet never used in synergy. With the aim to capture antibodies directly from crude extracts, a new approach combining precipitation and magnetic separation was developed and named as affinity magnetic precipitation. A precipitation screening, based on the Hofmeister series, and a commercial precipitation kit were tested with affinity magnetic particles to assess the best condition for antibody capture from human serum plasma and clarified cell supernatant. The best conditions were obtained when using PEG3350 as precipitant at 4°C for 1h, reaching 80% purity and 50% recovery of polyclonal antibodies from plasma, and 99% purity with 97% recovery yield of anti-TNFα mAb from cell supernatants. These results show that the synergetic use of precipitation and magnetic separation can represent an alternative for the efficient capture of antibodies. This article is protected by copyright. All rights reserved

BackgroundHalf of human cancers harbour TP53 mutations that render p53 inactive as a tumor suppressor. As such, reactivation of mutant (mut)p53 through restoration of wild-type (wt)-like function represents one of the most promising therapeutic strategies in cancer treatment. Recently, we have reported the (S)-tryptophanol-derived oxazoloisoindolinone SLMP53-1 as a new reactivator of wt and mutp53 R280K with in vitro and in vivo p53-dependent antitumor activity. The present work aimed a mechanistic elucidation of mutp53 reactivation by SLMP53-1.
Methods and results
By cellular thermal shift assay (CETSA), it is shown that SLMP53-1 induces wt and mutp53 R280K thermal stabilization, which is indicative of intermolecular interactions with these proteins. Accordingly, in silico studies of wt and mutp53 R280K DNA-binding domain with SLMP53-1 unveiled that the compound binds at the interface of the p53 homodimer with the DNA minor groove. Additionally, using yeast and p53-null tumor cells ectopically expressing distinct highly prevalent mutp53, the ability of SLMP53-1 to reactivate multiple mutp53 is evidenced.
Conclusions
SLMP53-1 is a p53-activating agent with the ability to directly target wt and a set of hotspot mutp53.
General Significance
This work reinforces the encouraging application of SLMP53-1 in the personalized treatment of cancer patients harboring distinct p53 status.

Three new additional skull specimens of Talarurus plicatospineus have been recovered from the Upper Cretaceous (Cenomanian–Santonian) Bayanshiree Formation, of Bayan Shiree cliffs, eastern Gobi Desert, Mongolia. The skulls feature unique characters such as an anteriorly protruded single internarial caputegulum, around 20 flat or concave nasal-area caputegulae surrounded by a wide sulcus, a vertically oriented elongate loreal caputegulum with a pitted surface, an elongate lacrimal caputegulum positioned above the posterodorsal border of the maxilla, two longitudinally arranged large frontoparietal caputegulae surrounded by smaller rhomboid caputegulae, small but elongate medial supraorbital caputegulae, a posterior supraorbital caputegulum that is four times larger than the anterior one, up to three transverse parallel grooves on the dorsal surface of the posterior supraorbital caputegulum, postocular caputegulae along the ventral to posterior rim of the orbit that extend almost to the anteroventral margin of the squamosal horn, a longitudinal furrow tapering towards the apex of the squamosal horn, a lateral nuchal caputegulum four to five times larger than other nuchal caputegulae, and a pterygovomerine keel with a ventral margin that is dorsally positioned to the alveolar ridge. The phylogenetic analysis result showed that Talarurus is sister to the clade that includes the derived Asian ankylosaurines (Saichania chulsanensis, Tarchia kielanae, and Zaraapelta nomadis). It also shows that there was dispersal of ankylosaurines from Asia into western North America before the Cenomanian. Moreover, the rostral differences between Talarurus and Tsagantegia, another ankylosaur from the same formation, suggest possible niche partitioning between these taxa.

Mathematics has a strong presence in the school curriculum, often justified by its usefulness in social life, in the world of work and by its connections with other sciences. This interdisciplinary connection, in particular when it requires constructing and refining mathematical models and discussing their applications to solve problems of other sciences, can assist students to understand why mathematics is so important in school. In the development of interdisciplinary activities, the characteristics of the tasks emerge as an important aspect. The emphasis is on the use of technological materials and the way they can support the development of concepts, provide different representations and support deeper understandings, and offer a multifaceted support to collect data and simulate experiences. Based on these assumptions, the aim of this chapter is to present, analyse and discuss tasks that promote interdisciplinary technological approaches from a mathematical point of view. In this chapter we assume interdisciplinarity as a complex construct, and in order to clarify its meaning we will discuss several types of conceptions, from multidisciplinary, to interdisciplinary, and to transdisciplinary. We will then address related concepts, such as modelling and STEM, highlighting similarities and differences between them, to reach an understanding of interdisciplinarity. In the process of the interdiciplinary approach, digital technologies arise as a central element. Based on a set of tasks on mathematics and on different sciences, we discuss what can change on an interdisciplinary approach to the teaching and learning of mathematical content and on the articulation between subjects.

Abstract An experimental work on reinforced concrete flat slab specimens to test the efficiency of postinstalled bolts, as punching shear reinforcement in resisting vertical and cyclic horizontal loads, was conducted and is presented in this paper. The test protocol consisted in increasing horizontal drifts combined with constant vertical load until failure. Two different detailing solutions for the shear reinforcement were considered, one using a radial distribution around the column and another using a cross distribution, being the results compared with a previously tested reference specimen. The dimensions of the specimens were 4.25 x 1.85 x 0.15 m3. The test setup used for these tests was developed by the research team and simulates the boundary conditions with already recognized good results. Postinstalled steel bolts were proven to be an efficient solution for strengthening of existing structures, improving the structural behavior, and the punching resistance.

Eucalyptus globulus Labill is a hardwood species of broad growth in temperate climates, which is receiving increasing interest for structural applications due to its high mechanical properties. Knowing the fracture behaviour is crucial to predict, through finite element models, the load carrying capacity of engineering designs with possibility of brittle failures such as elements with holes, notches, or certain types of joints. This behaviour can be adequately modelled on a macroscopic scale by the constitutive cohesive law. A direct identification of the cohesive law of Eucalyptus globulus L. in Mode II was performed by combining end-notched flexure (ENF) tests with digital image correlation (DIC) for radial-longitudinal crack propagation system. The critical strain energy release for this fracture mode, which represents the material toughness to crack-growth, was determined by applying the Compliance Based Beam Method (CBBM) as data reduction scheme and resulted in a mean value of 1.54 N/mm.