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Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022. The Author(s).

Spontaneous motion of liquid droplets can occur on hydrophobic, micro-structured, solid surfaces comprising a structural gradient. In this study, we examine such motion experimentally and explain our observations by invoking variable droplet–surface interactions (both actuation and resistance forces) arising from the structural gradient. The oscillatory motion of the droplet constitutes an integral aspect of the behaviour and this is incorporated into the overall modelling. The theoretical model features a truncated spheroid for the drop shape (flattened in the region of solid contact) coupled with the oscillatory and alternate leading and trailing motion of the contact line. Results from the model and experiments provide good qualitative and quantitative agreement. The component of the vertical oscillation is found to help overcome wetting hysteresis and actuate the motion, this being a key element for the completeness of the model.

Double cantilever beam (DCB) tests were performed on specimens consisting of aluminium substrates bonded with an epoxy adhesive film and containing strips of poor adhesion perpendicular to the crack propagation path. To achieve strong adhesion and cohesive failure in the adhesive in the nominal state, P2 etching protocol was used. Artificial adhesion defects were obtained by spraying PTFE particles, a dry lubricant, onto the substrate prior to bonding. Masks were used to control precisely the position and extent of the contaminated zones. The peculiar phenomenon attributed to such crack / defect interaction is an unstable/dynamic propagation regime. The crack onset and arrest conditions are investigated here by rewriting the energy balance analysis of the DCB test. More sophisticated numerical simulations were also performed for refined investigation of the dynamic crack propagation regime.

International audience; Liquid droplets move readily under the influence of surface tension gradients on their substrates. Substrates decorated with parallel microgrooves, or striations, presenting the advantage of homogeneous chemical properties yet varying the topological characteristics on either side of a straight-line boundary, are considered in this study. The basic type of geometry consists of hydrophobic micro-striations/rails perpendicular to the boundary, with the systematic variation of the width to spacing ratio, thus changing the solid–liquid contact fraction and inducing a well-defined wettability contrast across the boundary. Droplets in the Cassie–Baxter state, straddling the boundary, move along the wettability contrast in order to reduce the overall surface free energy. The results show the importance of the average solid fraction and contrasting fraction in a wide range of given geometries across the boundary on droplet motion. A unified criterion for contrasting striated surfaces, which describes the displacement and the velocity of the droplets, is suggested, providing guidelines for droplet manipulation on micro-striated/railed surfaces.The authors would like to acknowledge the support of the European Space Agency through ESA Contract No. 4000129506/20/NL/PG and the support received from the Engineering and Physical Sciences Research Council (EPSRC) through Grant No. EP/P005705/1. The authors also acknowledge the EC-RISE-ThermaSMART project, which received funding from the European Union's Horizon 2020 research and innovation program under Marie Skłodowska-Curie Grant Agreement No. 778104.

An important property affecting the integrity of a tyre is the adhesion between rubber and reinforcements such as metal cords. Standard tests used to evaluate rubber-metal adhesion fail to predict the intrinsic interfacial behaviour. A novel test protocol, referred to as the Rubber Cord Adhesion Inflation Test (RCAIT), has therefore been developed. In this work, RCAIT is used to compare the performance of four different adhesive systems (two rubber types and two cord coatings). In addition, the effect of fluid injection rate on crack propagation pressure is evaluated and is correlated to the sensitivity of the tensile behaviour of the rubber to strain rate. Some improvements in the RCAIT analysis are also proposed here. A thick rubber tube inflation model is proposed in conjunction with the Ogden model for hyperelastic behaviour that can be applied to other elastomeric models as well. In conclusion, the relationship between crack propagation speed and Critical Strain Energy Release Rate (SERR) is discussed.

A novel test configuration is proposed to characterize the adhesion between an elastomeric matrix and an included steel cord. The circular cylindrical, rubber envelope is bonded to the cord along the axis of symmetry. A crack is forced to propagate along the interface by inflating the rubber envelope using a pressurised liquid in between the two media. The constant pressure recorded during the test is used to evaluate the interfacial critical strain energy release rate (Critical SERR). This is achieved using an analytical model, taking into account both the incompressible, hyperelastic nature of the rubber and geometrical nonlinearity due to large deformations. An energy balance is proposed to evaluate the interfacial SERR.

The Rubber Cord Adhesion Inflation Test (RCAIT) is a recently proposed test protocol to study tyre rubber-steel cord fracture (Kane et al., 2019). As in the traditional blister test, a pressurised fluid is injected between the two adherends to propagate fracture. The fracture energy, Gc, is directly related to the strain energy stored in the inflated rubber. It was shown that evaluation of Gc for RCAIT depends intimately on how well the hyperelastic model is capable of predicting the rubber inflation condition (Kane et al., 2020). Here, a thick tube inflation model is proposed for a generalised, phenomenological, hyperelastic material. It is subsequently applied to RCAIT in order to study which data processing technique is likely to be the most reliable to evaluate the critical strain energy release rate of the specimen.

We examine the effects of nanoparticle addition at low concentration on the evaporation kinetics of droplets in the constant radius mode. The evaporative behaviour of deionized water and Al2O3 nanoparticle laden water on an aluminium substrate was observed at atmospheric and at different sub-atmospheric pressures. The two fluids exhibit the same evaporative behaviour, independent of the droplet volume or the sub-atmospheric pressure. Moreover, the linear relationship between evaporation rate and droplet radius, initially proposed by Picknett and Bexon nearly four decades ago for droplets evaporating in the constant radius mode, is satisfied for both liquids. In addition we have established a unified correlation solely function of fluid properties that extends this relationship to any sub-atmospheric pressure and fluid tested. We conclude that the addition of a small quantity of nanoparticles to the base fluid does not modify the kinetics of evaporation for pinned volatile droplets.

Small sessile drops of water containing either long or short strands of DNA ("biodrops") were deposited on silicon substrates and allowed to evaporate. Initially, the triple line (TL) of both types of droplet remained pinned but later receded. The TL recession mode continued at constant speed until almost the end of drop lifetime for the biodrops with Short DNA strands, whereas those containing long DNA strands entered a regime of significantly lower TL recession. We propose a tentative explanation of our observations based on free energy barriers to unpinning and increases in the viscosity of the base liquid due to the presence of DNA molecules. In addition, the structure of DNA deposits after evaporation was investigated by AFM. DNA self-assembly in a series of perpendicular and parallel orientations was observed near the contact line for the long-strand DNA, while, with the short-stranded DNA, smoother ring-stains with some nanostructuring but no striations were evident. At the interior of the deposits, dendritic and faceted crystals were formed from short and long strands, respectively, due to diffusion and nucleation limited processes, respectively. We suggest that the above results related to the biodrop drying and nanostructuring are indicative of the importance of DNA length, i.e., longer DNA chains consisting of linearly bonded shorter, rod-like DNA strands.

Retarded deformation at the bond line edge of a thick, viscoelastic adhesive layer is observed using digital image correlation. Such information is required for proposing physical crack onset/propagation parameters which take into account viscoelastic and viscous mechanisms in the evaluation of dissipated energy. A complex stress/strain redistribution is observed in the early stage after specimen loading. The results illustrate that viscoelasticity dissipates a considerable amount of energy prior to crack nucleation and the lack of predictive models to account for that phenomenon.