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The p53 tumor suppressor is widely found to be mutated in human cancer. This protein is regarded as a molecular hub regulating different cell responses, namely cell death. Compelling data have demonstrated that the impairment of p53 activity correlates with tumor development and maintenance. For these reasons, the reactivation of p53 function is regarded as a promising strategy to halt cancer. In the present work, the recombinant mutant p53R280K DNA binding domain (DBD) was produced for the first time, and its crystal structure was determined in the absence of DNA to a resolution of 2.0 Å. The solved structure contains four molecules in the asymmetric unit, four zinc(II) ions, and 336 water molecules. The structure was compared with the wild-type p53 DBD structure, isolated and in complex with DNA. These comparisons contributed to a deeper understanding of the mutant p53R280K structure, as well as the loss of DNA binding related to halted transcriptional activity. The structural information derived may also contribute to the rational design of mutant p53 reactivating molecules with potential application in cancer treatment.

The adhesively bonded joints behaviour under cyclic loading is not yet well understood due to its inherent complexity. Numerical approaches appear, therefore, as the easiest way to simulate such mechanical behaviour. In this work, double strap bonded joints with Carbon Fibres Reinforced Polymers (CFRP) and aluminium are numerically simulated and subjected to a cyclic loading history. In the numerical simulation, the Distinct Element Method (DEM) is used and it is assumed cohesive bi-linear bond-slip models with local damage of the interface. The evaluation of the bonded joints under cyclic loading is made by comparing the results with those simulated with a monotonic loading.

Concrete structures Externally Bonded Reinforced (EBR) with Fibre Reinforced Polymers (FRP) have been studied and used since the end of the last century. However, several issues need to be better studied in order to improve performance. The influence of size of anchorage plates used on Reinforced Concrete (RC) structures strengthened with EBR FRP composites, the external compressive stress to be applied on the anchorage plate and the numerical simulation of this region are some of the topics that need to be more carefully studied in order to clarify the performance of the FRP-to-concrete interface within the anchorage plate region. This study proposes a design methodology to estimate the amount of external compressive stress necessary to be applied on the anchorage plate of EBR systems with FRP composites, in order to avoid premature debonding. The external compressive stress imposed on the FRP composite is intended to simulate the effect produced by a mechanical anchorage system tightened to the EBR system. The results from the design proposal, when compared with the numerical ones, were efficient enough on the prediction of the bond strength improvement of FRP-to-concrete interfaces. © 2018 Elsevier Ltd

This study presents two alternative methods to determine the cohesive law of bovine cortical bone under mode II loading, employing the End Notched Flexure (ENF) test. The direct method results from the combination of the progress of the mode II strain energy release rate with the crack tip shear displacement, obtained by digital image correlation. The resulting cohesive law is determined by differentiation of this relation relatively to the crack shear displacement. The inverse method employs finite element analyses with cohesive zone modelling, in association with an optimization procedure. The resulting strategy enables determining the cohesive law without establishing a pre-defined shape. The significant conclusion that comes out of this work is that both methods offer consistent results regarding the estimation of the cohesive law in bone. Given that the inverse method dispenses the use of sophisticated equipment to obtain the cohesive law in bone, it can be used as a more convenient procedure to accomplish efficient studies in the context of bone fracture characterization under mode II loading.

This paper presents the determination of the crack resistance curve of the unidirectional carbon-epoxy composite material IM7-8552 for intralaminar fiber tensile failure under dynamic loading. The methodology, proposed by Catalanotti et al. (2014) for quasi-static loading conditions, was enhanced to high rate loading in the order of about 60 ?s-1. Dynamic tests were performed using a split-Hopkinson tension bar, while quasi-static reference tests were conducted on a standard electromechanical testing machine. Double-edge notched tension specimens of different sizes were tested to obtain the size effect law, which in combination with the concepts of the energy release rate is used to measure the entire crack resistance curve for the fiber tensile failure mode. Digital image correlation is applied to further verify the validity of the experiments performed at both static and dynamic loading. The data reduction methodology applied in this paper is suitable for intralaminar fiber failure modes without significant delamination. Sufficient proof is given that quasi-static fracture mechanics theory can also be used for the data reduction of the dynamic tests. It is shown, that the intralaminar fracture toughness for fiber tensile failure of UD IM7-8552 increases with increasing rate of loading.

The prediction of the fracture behaviour through reliable and practical criteria in the design of structural timber elements and connections has become of great importance and demands a proper fracture characterization of the material. Eucalyptus globulus Labill is envisioned as a hardwood species with great potential for high performance structural purposes because of its major mechanical and durability properties, being so far mainly used in paper industry. Experimental research on the identification of the resistance curves to derive the critical strain energy release rate in Eucalyptus globulus L. under pure mode I and RL crack propagation system is performed by means of Double Cantilever Beam tests. Three different data reduction schemes are compared: the Modified Experimental Compliance Method; and two approaches of the Compliance Based Beam Method. These methods take into account the non negligible damage mechanisms at the fracture process zone and have the advantage of being based exclusively on the specimen compliance following an equivalent crack concept, for which crack length monitoring during testing is not required. The Compliance Based Beam Method turns out to be the most appropriate data reduction scheme to obtain the critical energy release rate in eucalyptus because of its simplicity. Concerning this, a high average value of 720�J/m2 was obtained confirming Eucalyptus globulus L. as a promising hardwood species for timber structural design.

The monitoring of structures has undergone important advances with the improvements of digital cameras available on the market. Thus, the Digital Image Correlation (DIC) technique has become a viable way of studying engineering problems. Recently it has been used in the debonding failure process between the reinforcement and the substrate. The methods or methodologies that should be followed to obtain the results associated to the debonding phenomenon using the DIC technique need to be better understood and studies on this topic are scarce. The present work therefore proposes a new and inexpensive method to monitor the interfacial behaviour between a reinforcement material and a substrate by combining the use of the DIC technique and a simplified nonlinear bond-slip model. For the validation of the proposed method, a series of single-lap shear tests with a sufficient long bond length carried out by the authors are used. Based on the slip distribution obtained from the DIC technique, it was found that a third-degree polynomial function can be used to approximate the interfacial bond-slip curve of the joint. The validation of the model is made with several analytical solutions using the proposed bond-slip model. © 2018 Politechnika Wrocławska

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This work presents the results and the main conclusions of a series of experimental tests carried out to evaluate the efficiency of post-installed stainless steel reinforcement on the flexural strengthening of Reinforced Concrete (RC) T-beams when the bonding techniques EBR (Externally Bonded Reinforcement), NSM (Near Surface Mounted) and MA-EBR (EBR with Mechanical Anchors) are used. The RC T-beams were also modelled using a commercial Finite Element (FE) software in order to predict their behaviour until the rupture. For this purpose, a set of single-lap shear tests were also carried out to evaluate the local bond-slip relationships developed within the Stainless Steel (SS)-to-concrete interface. Due to the experimental bond-slip relationships, the numerical simulations were able to predict, with good accuracy, the different behaviours of the RC T-beams until their rupture. Moreover, the different rupture modes observed on all the RC T-beams herein tested were very well estimated by the numerical analyses. The tests of the RC T-beams showed that all the strengthening techniques allowed their flexural stiffness to be increased. Nevertheless, the RC T–beams strengthened with the EBR and NSM techniques had premature ruptures, i.e. the rupture in the RC T-beams occurred even before the yielding of their steel reinforcements. The RC T-beam strengthened with the MA-EBR technique showed good ductility and the highest load bearing capacity, which means that the MA-EBR technique is the best bonding technique herein used. © 2018 Elsevier Ltd

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