Interactions of glycan-specific epitopes to human lectin receptors represent novel immune checkpoints for investigating cancer and infection diseases. By employing a multidisciplinary approach that combines isothermal titration calorimetry, NMR spectroscopy, molecular dynamics simulations, and X-ray crystallography, we disclosed the molecular determinants that govern the recognition of the tumour and pathogenic glycobiomarker LacdiNAc (GalNAc?1-4GlcNAc, LDN), including their comparison with the ubiquitous LacNAc epitope (Gal?1-4GlcNAc, LN), by two human immune-related lectins, galectin-3 (hGal-3) and the macrophage galactose C-type lectin (hMGL). A different mechanism of binding and interactions is observed for the hGal-3/LDN and hMGL/LDN complexes, which explains the remarkable difference in the binding specificity of LDN and LN by these two lectins. The new structural clues reported herein are fundamental for the chemical design of mimetics targeting hGal-3/hMGL recognition process.

In this paper, we study partial automorphisms and, more generally, injective partial endomorphisms of a finite undirected path from Semigroup Theory perspective. Our main objective is to give formulas for the ranks of the monoids IEnd(P_n) and PAut(P_n) of all injective partial endomorphisms and of all partial automorphisms of the undirected path P_n with n vertices. We also describe Green's relations of PAut(P_n) and IEnd(P_n) and calculate their cardinals.

This chapter aims to make more explicit the grounded or ‘pragmatic theories’ that inform the design of mathematics teachers’ professional development (PD) to exploit technological affordances. It uses aspects of some representative projects that took place in four countries (Colombia, Italy, Mexico, and Portugal) to illustrate lessons learned (e.g., similarities and differences, barriers and opportunities) and provide important insights to inform future PD implementations. To do this, we have identified a set of aspects (and sub-aspects) that emerged in relation to five major themes and reveal our ‘pragmatic theories’ alongside a consideration of the interconnections between these aspects. Our contribution offers a methodological frame to support future PD designs for teachers of mathematics concerning digital technology uses.

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The Cellulosome is an intricate macromolecular protein complex that centralizes the cellulolytic efforts of many anaerobic microorganisms through the promotion of enzyme synergy and protein stability. The assembly of numerous carbohydrate processing enzymes into a macromolecular multiprotein structure results from the interaction of enzyme-borne dockerin modules with repeated cohesin modules present in noncatalytic scaffold proteins, termed scaffoldins. Cohesin–dockerin (Coh-Doc) modules are typically classified into different types, depending on structural conformation and cellulosome role. Thus, type I Coh-Doc complexes are usually responsible for enzyme integration into the cellulosome, while type II Coh-Doc complexes tether the cellulosome to the bacterial wall. In contrast to other known cellulosomes, cohesin types from Bacteroides cellulosolvens, a cellulosome-producing bacterium capable of utilizing cellulose and cellobiose as carbon sources, are reversed for all scaffoldins, i.e., the type II cohesins are located on the enzyme-integrating primary scaffoldin, whereas the type I cohesins are located on the anchoring scaffoldins. It has been previously shown that type I B. cellulosolvens interactions possess a dual-binding mode that adds flexibility to scaffoldin assembly. Herein, we report the structural mechanism of enzyme recruitment into B. cellulosolvens cellulosome and the identification of the molecular determinants of its type II cohesin–dockerin interactions. The results indicate that, unlike other type II complexes, these possess a dual-binding mode of interaction, akin to type I complexes. Therefore, the plasticity of dual-binding mode interactions seems to play a pivotal role in the assembly of B. cellulosolvens cellulosome, which is consistent with its unmatched complexity and size.

This paper deals with the determination of upper and lower bounds for the three-dimensional undrained stability of shallow tunnels. The tunnel is circular and a distance between its face and its lining is considered. The soil shear strength is modeled using the Tresca criterion. Results of the upper and lower bounds of the stability number are presented, for several geometrical and resistance configurations and their comparison with previous results is made, showing the clear improvement obtained. Finally, equations approaching the stability number are proposed.

Journal of Trace Elements in Medicine and Biology, 68 (2021) 126837. doi:10.1016/j.jtemb.2021.126837

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

The SOUL, or heme-binding protein HBP/SOUL, family represents a group of evolutionary conserved putative heme-binding proteins that contains a number of members in animal, plant andbacterial species. The structures of the murine form of HEBP1, or p22HBP, and the human form of HEBP2, or SOUL, have been determined in 2006 and 2011 respectively. In this work we discuss the structures of HEBP1 and HEBP2 in light of new X-ray data for heme bound murine HEBP1. The interaction between tetrapyrroles and HEBP1, initially proven to be hydrophobic in nature, was thought to also involve electrostatic interactions between heme propionate groups and positively charged amino acid side chains. However, the new X-ray structure, and results from murine HEBP1 variants and human HEBP1, confirm the hydrophobic nature of the heme-HEBP1 interaction, resulting in Kd values in the low nanomolar range, and rules out any electrostatic stabilization. Results from NMR relaxation time measurements for human HEBP1 describe a rigid globular protein with no change in motional regime upon heme binding. X-ray structures deposited in the PDB for human HEBP2 are very similar to each other and to the new heme-bound murine HEBP1 X-ray structure (backbone rmsd ca. 1 {\AA}). Results from a HSQC spectrum centred on the histidine side chain N$δ$-proton region for HEBP2 confirm that HEBP2 does not bind heme via H42 as no chemical shift differences were observed upon heme addition for backbone NH and N$δ$ protons. A survey of the functions attributed to HEBP1 and HEBP2 over the last 20 years span a wide range of cellular pathways. Interestingly, many of them are specific to higher eukaryotes, particularly mammals and a potential link between heme release under oxidative stress and human HEBP1 is also examined using recent data. However, at the present moment, trying to relate function to the involvement of heme or tetrapyrrole binding, specifically, makes little sense with our current biological knowledge and can only be applied to HEBP1, as HEBP2 does not interact with heme. We suggest that it may not be justified to call this very small family of proteins, heme-binding proteins. The family may be more correctly called “the SOUL family of proteins related to cellular fate” as, even though only HEBP1 binds heme tightly, both proteins may be involved in cell survival and/or proliferation.

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

The Industry 4.0 addresses a radical change on business processes. Through communication technology, objects interact with each other; the physical and digital worlds merge. This makes an environment more flexible, allowing to respond faster to specific customer requirements. Therefore, businesses need to rapidly adapt to avoid being left behind. A business model is required to meet the new concepts of Industry 4.0. In addition, lean and green characteristics may align with business model elements. Understanding how these concepts interact is something that need clarification. Based on literature review, a conceptual relationship between Business Model (Canvas), Lean and green management approach and Industry 4.0 approach is presented. Lean and green management characteristics are identified to be aligned through a Business Model Canvas perspective. Also, the concepts of the Industry 4.0 can be applied in each element of the Business Model Canvas. Managers and entrepreneurs can create, design or redefine their business knowing the lean and green application and Industry 4.0 execution. This research aims to contribute to the discussion of the relationships between these concepts. To the authors’ knowledge, this work is one of the first to try to relate these concepts.

In this work, we aim at achieving the most accurate quantitative determination of elements in human tissues by means of X-ray Fluorescence spectrometry using the external calibration approach. A calibration curve built using a set of certified reference materials (CRM) of animal tissue was compared with the one obtained with a set of CRMs of plants and leaves with lower atomic number Z but with correction of the matrix using the scattering peaks of the X-ray tube anode. Finally, a calibration curve combining the two sets of CRMs was built and the accuracy of the quantification using the three methods was compared and a more precise method of quantification was obtained. This improved approach was tested on five paired samples of normal and tumour human tissue. Despite the high heterogeneity of the samples, and given the improvement in accuracy of the measurements, significant differences were found in the elemental concentration of low-Z elements. This journal is

Co-sputtering of SiO2 and high-$ąppa$ Ta2O5 was used to make multicomponent gate dielectric stacks for In-Ga-Zn-O thin-film transistors (IGZO TFTs) under an overall low thermal budget (T = 150 °C). Characterization of the multicomponent layers and of the TFTs working characteristics (employing them) was performed in terms of static performance, reliability, and stability to understand the role of the incorporation of the high-$ąppa$ material in the gate dielectric stack. It is shown that inherent disadvantages of the high-$ąppa$ material, such as poorer interface properties and poor gate insulation, can be counterbalanced by inclusion of SiO2 both mixed with Ta2O5 and as thin interfacial layers. A stack comprising a (Ta2O5)x(SiO2)100 − x film with x = 69 and a thin SiO2 film at the interface with IGZO resulted in the best performing TFTs, with field-effect mobility (µFE) ≈ 16 cm2·V−1·s−1, subthreshold slope (SS) ≈ 0.15 V/dec and on/off ratio exceeding 107. Anomalous Vth shifts were observed during positive gate bias stress (PGBS), followed by very slow recoveries (time constant exceeding 8 × 105 s), and analysis of the stress and recovery processes for the different gate dielectric stacks showed that the relevant mechanism is not dominated by the interfaces but seems to be related to the migration of charged species in the dielectric. The incorporation of additional SiO2 layers into the gate dielectric stack is shown to effectively counterbalance this anomalous shift. This multilayered gate dielectric stack approach is in line with both the large area and the flexible electronics needs, yielding reliable devices with performance suitable for successful integration on new electronic applications.

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.

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.

In this paper we study the widely considered endomorphisms and weak endomorphisms of a finite undirected path from monoid generators perspective. Our main aim is to determine the ranks of the monoids $wEnd P_n$ and $End P_n$ of all weak endomorphisms and all endomorphisms of the undirected path $P_n$ with $n$ vertices. We also consider strong and strong weak endomorphisms of $P_n$.