Silk fibroin is a biobased material with excellent biocompatibility and mechanical properties, but its use in bioelectronics is hampered by the difficult dissolution and low intrinsic conductivity. Some ionic liquids are known to dissolve fibroin but removed after fibroin processing. However, ionic liquids and fibroin can cooperatively give rise to functional materials, and there are untapped opportunities in this combination. The dissolution of fibroin, followed by gelation, in designer ionic liquids from the imidazolium chloride family with varied alkyl chain lengths (2–10 carbons) is shown here. The alkyl chain length of the anion has a large impact on fibroin secondary structure which adopts unconventional arrangements, yielding robust gels with distinct hierarchical organization. Furthermore, and due to their remarkable air-stability and ionic conductivity, fibroin ionogels are exploited as active electrical gas sensors in an electronic nose revealing the unravelled possibilities of fibroin in soft and flexible electronics.

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.

Since the 1970s, the application of microprocessor in industrial machinery and the development of computer systems have transformed the manufacturing landscape. The rapid integration and automation of production systems have outpaced the development of suitable human design criteria, creating a deepening gap between humans and systems in which human was seen as an important source of errors and disruptions. Today, the situation seems different: the scientific and public debate about the concept of Industry 4.0 has raised awareness about the central role humans have to play in manufacturing systems, the design of which must be considered from the very beginning. The future of industrial systems, as represented by Industry 4.0, will rely on the convergence of several research fields such as Intelligent Manufacturing Systems (IMS), Cyber-Physical Systems (CPS), Internet of Things (IoT), but also socio-technical fields such as social approaches within technical systems. This article deals with different human social dimensions associated with CPS and IoT and focuses on their conceptual evolution regarding automated production systems’ sociability, notably by bringing humans back in the loop. Hereby, this paper aims to take stock of current research trends to show the importance of integrating human operators as a part of a socio-technical system based autonomous and intelligent products or resources. Consequently, different models of sociability as a way to integrate humans in the broad sense and/or the develop future automated production systems have been identified from the literature and analysed.

Regime switching diffusion processes with one or two thresholds and regime switching occurring by a change in the diffusion drift and/or volatility functions parameters of a stochastic differential equation, whose solution defines a continuous time diffusion process, were defined in previous works; the change in regime occurring whenever the trajectory of the process crosses a threshold, possibly with some delay. In this paper we generalise the previous
results by allowing the underlying diffusion process to change from one family of diffusions in one regime to an entirely different one in the other regime; these families of diffusions are characterised by specific functional forms for drift and volatility coefficients depending on parameters. We propose an estimation procedure for all the parameters, namely the thresholds, the delay and, for both regimes, diffusion’s parameters and we apply the introduced estimation procedure to both simulated and real data.

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Abstract Fiber reinforced polymer (FRP) composites can be efficient for flexural strengthening of flat slabs if debonding of the FRP is postponed. However, with the increase of the flexural capacity, the flat slab becomes more susceptible to punching shear failure. In this context, four flexural or simultaneous flexural and punching shear retrofitting systems are investigated in this study to strengthen a flexure-deficient flat slab. Externally Bonded Reinforcement on Grooves (EBROG) and externally bonded reinforcement (EBR) methods are used for flexural strengthening in two cases: slabs without punching shear reinforcement and with post-installed shear bolts as shear reinforcement. According to the results, flexural strengthening of the slab using the EBR and EBROG techniques increased its load capacity by 12% and 21%, respectively. Simultaneous flexural and shear strengthening of the slab using the EBROG technique was the most effective, leading to a 57% enhancement of the load capacity. For specimens whose failure was governed by punching, comparing the results with code predictions showed that Eurocode and ACI (and the respective guide documents fib bulletin 90 and ACI 440.2R) overestimated the capacity of these specimens. In cases where failure was governed by flexure, a simple application of the yield line theory predicted reasonably well the load capacity of the specimens.

Microstructured transparent conductive oxides (TCOs) have shown great potential as photonic electrodes in photovoltaic (PV) applications, providing both optical and electrical improvements in the solar cells’ performance due to: (1) strong light trapping effects that enhance broadband light absorption in PV material and (2) the reduced sheet resistance of the front illuminated contact. This work developed a method for the fabrication and optimization of wavelength-sized indium zinc oxide (IZO) microstructures, which were soft-patterned on flexible indium tin oxide (ITO)-coated poly(ethylene terephthalate) (PET) substrates via a simple, low-cost, versatile, and highly scalable colloidal lithography process. Using this method, the ITO-coated PET substrates patterned with IZO micro-meshes provided improved transparent electrodes endowed with strong light interaction effects—namely, a pronounced light scattering performance (diffuse transmittance up to  50%). In addition, the photonic-structured IZO mesh allowed a higher volume of TCO material in the electrode while maintaining the desired transparency, which led to a sheet resistance reduction (by  30%), thereby providing further electrical benefits due to the improvement of the contact conductance. The results reported herein pave the way for a new class of photonic transparent electrodes endowed with mechanical flexibility that offer strong potential not only as advanced front contacts for thin-film bendable solar cells but also for a much broader range of optoelectronic applications.

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.

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.