Acrylamide is a neurotoxic and carcinogenic organic compound that is able to bind to several biomolecules and form adducts, through nucleophilic addition and in vivo by the Maillard Reaction, interfering with the biological functions of these molecules. Hemoglobin is one of the most abundant intracellular blood proteins, and thus it is of high interest to understand whether the binding of acrylamide can alter its properties. The interaction of acrylamide with hemoglobin was assessed in a 20:1 ratio, and after a 72 h-incubation period, a decrease of ca. 50% in the absorbance of the hemoglobin's Soret band was observed at 37 °C. This together with the analysis of circular dichroism spectra indicate that acrylamide binds in close proximity to the heme group. These perturbations were confirmed to not correspond to the loss of the heme group and were mostly reverted after passing the protein through a size-exclusion chromatographic matrix, suggesting a dominant non-covalent interaction for the observed effect. The thermodynamic parameters of unfolding in the absence and presence of acrylamide, suggest an interaction based on H-bonds and van der Waals forces that slightly stabilizes hemoglobin. The oxygen binding capacity of hemoglobin does not seem to be hindered, as no differences in the Q bands were observed in the adduct.

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.

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 $P_n$.

The aim of the paper is to present and analyse the case of one teacher attempting to introduce his students to fractals using digital technology. His task design process has been made explicit through the writing of a storyboard. It has been analysed in order to focus on the stages of the process, identifying prominent elements in it by using the knowledge quartet framework. Results can be useful to inform teacher educators about his needs with respect to the development of his ability in task design. The importance of this aspect, particularly worth of note in the digital age in which teachers have many opportunities to access teaching resources online, has been amplified by the constraints to which educational systems have been subjected during the Covid-19 pandemic emergency.

This paper studies the influence of different longitudinal top reinforcement detailing on the behaviour and punching capacity of flat slabs. Experimental and numerical studies were carried out. The experimental campaign consisted in testing three reinforced concrete slabs 2.20 m wide with a thickness equal to 0.15 m. The numerical study was conducted using the non-linear finite element software ATENA 3D. Using numerical models, which were calibrated using the experimental tests, a parametric study was carried out to include other design solutions beyond the tested ones. The parameters that were changed in this parametric study were the steel reinforcement ratio, the concrete strength and the detailing of the top steel reinforcement, namely using a solution with uniform distribution and other with a higher concentration of reinforcement near the column. Finally, the results were compared with predictions obtained using some of the existing codes (Eurocode 2 and Model Code 2010). From this study it can be concluded that concentrating the top flexural reinforcement, keeping the same total amount of top longitudinal reinforcement, results in a stiffer response, an increment in the punching resistance, and a decrease in the maximum vertical displacement.

The cyclic failure observed in structural components such as pipelines subjected to extreme loading conditions highlights some limitations concerning the application of existing fatigue damage models. The evaluation and prediction of this type of failure in these steel components under large-scale plastic yielding associated with high levels of stress triaxiality are not sufficiently known nor explored. This fatigue domain is conventionally called ultra-low-cycle fatigue (ULCF) and damage features are representative of both low-cycle fatigue (LCF) and monotonic ductile fracture. Thus, in order to understand the ULCF damage mechanisms both monotonic and LCF tests are required to get representative bounding damage information to model the material damage behaviour under such extreme loading conditions. This paper aims at exploring the Theory of Critical Distances (TCD) in the LCF and ULCF fatigue regimes, including the application of the point, line and area methods. The application of the TCD theories has not been explored so far in the ULCF fatigue regimes, despite its promising results in the LCF and high-cycle fatigue. An experimental program was carried out on several specimens’ geometries made of X52 piping steel. In detail, smooth plane specimens and notched plane specimens were cyclic loaded under tension/compression loading in order to obtain fatigue lives within the range of 101-104 cycles. In addition, cyclic bending tests on notched plane specimens were also incorporated in this study. Finite element simulations of all small-scale tests were conducted allowing to derive elastoplastic stress/strain fields along the potential crack paths. The numerical data were subjected to a post-processing in order to find characteristic lengths that can be treated as a fatigue property according to the TCD. A unified strain-life relation is proposed for the X52 piping steel together with a characteristic material length, consisting of a practical relation for pipeline strain-based design under extreme cyclic loading conditions.

This work studies the low-velocity impact response of 3D-printed layered structures made of thermoplastic materials (PLA and PETg), which form sacrificial claddings for impact protection. The analyzed structures are composed of crushable cellular cores placed in between terminal stiffening plates. The cores tessellate either honeycomb hexagonal unit cells, or hexagonal cells with re-entrant corners, with the latter exhibiting auxetic response. The given results highlight that the examined PETg protectors exhibit higher energy dissipation ratios and lower restitution coefficients, as compared to PLA structures that have the same geometry. It is concluded that PETg qualifies as an useful material for the fabrication of effective impact protection gear through ordinary, low-cost 3D printers.