Nematicity at the Hund's metal crossover in iron superconductors

The theoretical understanding of the nematic state of iron-based superconductors and especially of FeSe is still a puzzling problem. Although a number of experiments call for a prominent role of local correlations and place iron superconductors at the entrance of a Hund's metal state, the effect of the electronic correlations on the nematic state has been theoretically poorly investigated. In this work we study the nematic phase of iron superconductors accounting for local correlations, including the effect of the Hund's coupling. We show that Hund's physics strongly affects the nematic properties of the system. It severely constrains the precise nature of the feasible orbital-ordered state and induces a differentiation in the effective masses of the zx/yz orbitals in the nematic phase. The latter effect leads to distinctive signatures in different experimental probes overlooked so far in the interpretation of experiments. As notable examples the splittings between zx and yz bands at \u393 and M points are modified, with important consequences for angle-resolved photoemission spectroscopy measurements

insights into the definition of terms in european medical device regulation

ABSTRACTIntroduction: Medical devices comprise apparatus/instruments, software, and materials with therapeutic activities obtained by principal mechanisms of action different from pharmacological, immunological and metabolic, which are proper of medicinal products. In this context the key for the distinction between medicinal products and devices lies in the correct interpretation of these terms, which, although defined in a guideline, are still not univocally interpreted.Areas covered: This article discusses the definitions of pharmacological and non-pharmacological mechanisms of action, such as the chemical and physical means. The aim is to give insights on the correct definition these terms in order to contribute to build the desired synergy between scientific and regulatory fields and promote a correct interpretation of the European regulatory framework as well as sustainable health and innovation.Expert commentary: We propose a series of definitions and a method to interpret those definitions within ..

Fernandez Blanco, T,; Gonzales Roel, V.; Capone, R.; Branchetti, L.; Gaio, A. Inprasitha, M., Changsri, N. & Boonsena, N. (Eds). SYMMETRY-ART: A STEAM TRAINING WORKSHOP FOR PRIMARY SCHOOL TEACHERS (2020). Interim Proceedings of the 44th Conference of the International Group for the Psychology of Mathematics Education. Khon Kaen, Thailand: PME.

The aim of this paper is to analyse a symmetry and art workshop from a STEAM perspective. The theoretical framework of the Meta-Didactical Transposition is taken as a reference. The sample consists of seven Primary School teachers. A qualitative methodology is followed that is developed in four phases: learning, planning, implementation and reflection. The results show that the teachers are not flexible in dealing with the different conceptions of symmetry and the creative aspect of the workshop. In general, there is a positive attitude towards the interdisciplinary character of the workshop, despite the fact that they were not able to connect both disciplines in a balanced way

Charge Disproportionation, Mixed Valence, and Janus Effect in Multiorbital Systems: A Tale of Two Insulators

Multiorbital Hubbard models host strongly correlated "Hund's metals" even for interactions much stronger than the bandwidth. We characterize this interaction-resilient metal as a mixed-valence state. In particular, it can be pictured as a bridge between two strongly correlated insulators: a high-spin Mott insulator and a charge-disproportionated insulator which is stabilized by a very large Hund's coupling. This picture is confirmed comparing models with negative and positive Hund's coupling for different fillings. Our results provide a characterization of the Hund's metal state and connect its presence with charge disproportionation, which has indeed been observed in chromates and proposed to play a role in iron-based superconductors

Human neutrophils activated via TLR8 promote Th17 polarization through IL-23

Human neutrophils contribute to the regulation of inflammation via the generation of a range of cytokines that affect all elements of the immune system. Here, we investigated their ability to express some of the members of the IL‐12 family after incubation with TLR8 agonists. Highly pure human neutrophils were thus incubated for up to 48 h with or without R848, or other TLR8 agonists, to then measure the expression levels of transcripts and proteins for IL‐12 family member subunits by RNA‐seq, reverse transcription quantitative PCR, and ELISA. We show a TLR8‐mediated inducible expression of IL‐12B and IL‐23A, but not IL‐12A, mRNA, which occurs via chromatin remodeling (as assessed by ChIP‐seq), and subsequent production of IL‐23 and IL‐12B, but no IL‐12, proteins. Induction of IL‐23 requires endogenous TNF‐α, as both mRNA and protein levels were blocked in TLR8‐activated neutrophils via a TNF‐α‐neutralizing Ab. We also show that supernatants from TLR8‐activated neutrophils, but not autologous monocytes, induce the differentiation of Th17 cells from naïve T cells in an IL‐23‐dependent fashion. This study unequivocally demonstrates that highly pure human neutrophils express and produce IL‐23, further supporting the key roles played by these cells in the important IL‐17/IL‐23 network and Th17 responses

Mesenchymal stem cells are enriched in head neck squamous cell carcinoma, correlates with tumour size and inhibit T-cell proliferation

BACKGROUND: Cancer is a multifactorial disease not only restricted to transformed epithelium, but also involving cells of the immune system and cells of mesenchymal origin, particularly mesenchymal stem cells (MSCs). Mesenchymal stem cells contribute to blood- and lymph- neoangiogenesis, generate myofibroblasts, with pro-invasive activity and may suppress anti-tumour immunity. METHODS: In this paper, we evaluated the presence and features of MSCs isolated from human head neck squamous cell carcinoma (HNSCC). RESULTS: Fresh specimens of HNSCC showed higher proportions of CD90+ cells compared with normal tissue; these cells co-expressed CD29, CD105, and CD73, but not CD31, CD45, CD133, and human epithelial antigen similarly to bone marrow-derived MSCs (BM-MSCs). Adherent stromal cells isolated from tumour shared also differentiation potential with BM-MSCs, thus we named them as tumour-MSCs. Interestingly, tumour-MSCs showed a clear immunosuppressive activity on in vitro stimulated T lymphocytes, mainly mediated by indoelamine 2,3 dioxygenase activity, like BM-MSCs. To evaluate their possible role in tumour growth in vivo, we correlated tumour-MSC proportions with neoplasm size. Tumour-MSCs frequency directly correlated with tumour volume and inversely with the frequency of tumour-infiltrating leukocytes. CONCLUSIONS: These data support the concept that tumour-MSCs may favour tumour growth not only through their effect on stromal development, but also by inhibiting the anti-tumour immune response

Experimental Paradigm for the Assessment of the Non-pharmacological Mechanism of Action in Medical Device Classification: The Example of Glycerine as Laxative

The evolution of medical devices has led to the introduction of medical devices that include “substances” and which, due to their presentation and sites of application may resemble medicinal products. The difference between substance-based medical devices and medicinal products lies in the proper definition of the principal mechanism of action. The major problem at the moment is the lack of a proper procedure for the demonstration of a mechanism that is “not pharmacological, immunological or metabolic.” We aimed to design an experimental set up to demonstrate the difference between the mechanism of action of two substances used commonly for the treatment of constipation, lubiprostone (example of medicinal product) and glycerine (example of medical device). By implementing cellular models and molecular analyses we demonstrate the difference in their mechanism of action. This set up can be considered an example on the possibility to define a paradigm for the case by case study of the mechanism of action of substances and combination of substances in medical devices

Ultrafast orbital manipulation and Mott physics in multi-band correlated materials

Multiorbital correlated materials are often on the verge of multiple electronic phases (metallic, insulating, superconducting, charge and orbitally ordered), which can be explored and controlled by small changes of the external parameters. The use of ultrashort light pulses as a mean to transiently modify the band population is leading to fundamentally new results. In this paper we will review recent advances in the field and we will discuss the possibility of manipulating the orbital polarization in correlated multi-band solid state systems. This technique can provide new understanding of the ground state properties of many interesting classes of quantum materials and offers a new tool to induce transient emergent properties with no counterpart at equilibrium. We will address: the discovery of high-energy Mottness in superconducting copper oxides and its impact on our understanding of the cuprate phase diagram; the instability of the Mott insulating phase in photoexcited vanadium oxides; the manipulation of orbital-selective correlations in iron-based superconductors; the pumping of local electronic excitons and the consequent transient effective quasiparticle cooling in alkali-doped fullerides. Finally, we will discuss a novel route to manipulate the orbital polarization in a a k-resolved fashion

Epi-Regulation of Cell Death in Cancer

How do organisms regulate the correct balance between the production of “new” cells and the elimination of the “old” ones, remains an important biology issue under investigation. Cell(s) death represents a fundamental process involved in organism development and cell homeostasis, whose alteration is considered one hallmark of cancer and lead to drug resistance and consequently treatment failure. The recent re-classification of cell death has identified new molecular programs in which several proteins have a pivotal role. Several studies have highlighted a direct link between epigenetic modifications and cell death mechanisms. Different epi-modifications have been described, capable of regulating diverse key players implicated in cell death, leading to uncontrolled proliferation of cancer cells. Scientific efforts are focused on the understanding the epigenetic regulation of cell death mechanisms by developing tools and/or new epi-molecules able to overcome cell death resistance. The development of new epi-molecular tools can overcome cell death deregulation thus potentially improving the sensitivity to the anti-tumor therapies. This chapter focuses on the main epigenetic deregulations in cell death mechanisms in cancer

Chitinase 3-like-1 is produced by human Th17 cells and correlates with the level of inflammation in juvenile idiopathic arthritis patients

Background: CHI3L1 is a chitinase-like protein without enzymatic activity, produced by activated macrophages, chondrocytes, neutrophils. Recent studies on arthritis, asthma, and inflammatory bowel diseases suggest that chitinases are important in inflammatory processes and tissue remodeling, but their production by human T cells, has never been reported. Methods: A microarray analysis of gene expression profile was performed on Th17 and classic Th1 cell clones and CHI3L1 was found among the up-regulated genes on Th17 cells. Different types of helper T cell clones (TCCs) were then evaluated by Real Time PCR (RT-PCR) for CHI3L1 mRNA expression; protein expression was investigated in cell lysates by western blotting and in cultures supernatants by ELISA. ELISA was also used to measure CHI3L1 in the serum and in the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients. Results: At mRNA level CHI3L1 was highly expressed by Th17, Th17/Th1, non classic Th1 and even in Th17/Th2 cell clones, whereas it was virtually absent in CD161- classic Th1 and Th2 TCCs. CHI3L1 was also detected in cell culture supernatants of Th17 and Th17-derived cells but not of classic Th1. Moreover CHI3L1 was higher in the SF than in serum of JIA patients, and it positively correlated with the frequency of Th17 and non-classic Th1 cells in SF. CHI3L1 in SF also positively correlated with the C reactive protein (CRP) serum levels, and with the levels of some proinflammatory cytokines, such as IL-6 and p40, which is the common subunit of IL12 and IL23. Conclusions: Here we describe for the first time CHI3L1 production by T cells owing the Th17 family. Moreover the positive correlation found between the frequency of Th17 and Th17-derived cell subsets and CHI3L1 levels in SF of JIA patients, in agreement with the suggested role of these cells in inflammatory process, candidates CHI3L1 as a possible biological target in JIA treatment