In-plane stiffness of timber floors strengthened with CLT

Five full-scale timber floors were tested in order to analyse the in-plane behaviour of these structural systems. The main objective was an assessment of the effectiveness of in-plane strengthening using cross-laminated timber (CLT). To this end, one unstrengthened specimen (original), one specimen strengthened with a second layer of floorboards, two specimens strengthened with three CLT panels, and one specimen strengthened with two CLT panels, were tested. A numerical analysis was then performed in order to analyse the composite behaviour of the timber floors in more detail. Due to its importance as regards composite behaviour, the first phase of the experimental programme was composed of push-out tests on specimens representing the shear connection between the timber beams and the CLT panels. This paper describes the tests performed and the numerical modelling applied to evaluate the composite behaviour of the strengthened timber floors. The use of CLT panels is revealed to be an effective way to increase the in-plane stiffness of timber floors, through which the behaviour of the composite structure can be significantly changed, depending on the connection applied, or modified as required.

Extreme value Birnbaum-Saunders regression models applied to environmental data

Extreme value models are widely used in different areas. The Birnbaum–Saunders distribution is receiving considerable attention due to its physical arguments and its good properties. We propose a methodology based on extreme value Birnbaum–Saunders regression models, which includes model formulation, estimation, inference and checking. We further conduct a simulation study for evaluating its performance. A statistical analysis with real-world extreme value environmental data using the methodology is provided as illustration.

MET is required for the recruitment of anti-tumoural neutrophils

Mutations or amplification of the MET proto-oncogene are involved in the pathogenesis of several tumours, which rely on the constitutive engagement of this pathway for their growth and survival. However, MET is expressed not only by cancer cells but also by tumour-associated stromal cells, although its precise role in this compartment is not well characterized. Here we show that MET is required for neutrophil chemoattraction and cytotoxicity in response to its ligand hepatocyte growth factor (HGF). Met deletion in mouse neutrophils enhances tumour growth and metastasis. This phenotype correlates with reduced neutrophil infiltration to both the primary tumour and metastatic sites. Similarly, Met is necessary for neutrophil transudation during colitis, skin rash or peritonitis. Mechanistically, Met is induced by tumour-derived tumour necrosis factor (TNF)-a or other inflammatory stimuli in both mouse and human neutrophils. This induction is instrumental for neutrophil transmigration across an activated endothelium and for inducible nitric oxide synthase production upon HGF stimulation. Consequently, HGF/MET-dependent nitric oxide release by neutrophils promotes cancer cell killing, which abates tumour growth and metastasis. After systemic administration of a MET kinase inhibitor, we prove that the therapeutic benefit of MET targeting in cancer cells is partly countered by the pro-tumoural effect arising from MET blockade in neutrophils. Our work identifies an unprecedented role of MET in neutrophils, suggests a potential 'Achilles' heel' of MET-targeted therapies in cancer, and supports the rationale for evaluating anti-MET drugs in certain inflammatory diseases.