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Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. General estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC>0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses.

BACKGROUND Amide proton transfer (APT) imaging is a chemical exchange saturation transfer (CEST) technique offering potential clinical applications in patients with brain tumors. PURPOSE To investigate whether cerebral APT-CEST is sufficiently reproducible in healthy tissue and glioma for clinical use at 3T. STUDY TYPE Prospective, longitudinal SUBJECTS Twenty-one healthy volunteers (M:F = 10:11; age 39±11 years) and six glioma patients (M:F = 3:3; age 50±17 years: four glioblastomas, one oligodendroglioma, one suspected low-grade glioma). FIELD STRENGTH/SEQUENCE 3T, SPACE-CEST ASSESSMENT APT-CEST measurement reproducibility was assessed within-session (glioma patients, healthy volunteers), and between-sessions and between-days (healthy volunteers). The standard deviation of the within-subject difference (SDdiff) was calculated in tumor regions of interest (ROI), and eight ROIs at relevant locations including a whole-brain ROI. STATISTICAL TESTS Brown-Forsythe tests and variance component analyses (VCA) were used to assess the reproducibility of ROIs for the three reproducibility time intervals. Intraclass correlation coefficient (ICC) was used to assess agreement between the ROIs for the three reproducibility time intervals. RESULTS APT-CEST magnetization transfer ratio asymmetry (MTRasym) was 0.89±0.96% on average in healthy brain tissue and 1.59±0.67% in tumor tissue. Intratumoral mean MTRasym was significantly higher than MTRasym in healthy-appearing tissue in patients (0.5±0.46%; P< 0.001). The APTCEST difference between GBMs and contralateral tissue was 1.11%. The average within-session, between-sessions, and between-days SDdiff of healthy control brains was 0.2%. The within-session SDdiff of whole-brain was 0.2% in both healthy volunteers and patients, and 0.21% in the segmented tumor. The orbitofrontal gyri were the ROI with the highest within-session SDdiff (0.61%). Within-session reproducibility of ROIs did not differ significantly from between-sessions or between-day reproducibility (0.76>P>0.22) and VCA showed that within-session variance was the most important factor (60%), but differed from between-days reproducibility in putamen and the central brain (P

International audience; A combined experimental and numerical investigation of the roughness of intergranular cracks in two-dimensional disordered solids is presented. We focus on brittle materials for which the characteristic length scale of damage is much smaller than the grain size. Surprisingly, brittle cracks do not follow a persistent path with a roughness exponent ζ ≈ 0.6-0.7 as reported for a large range of materials. Instead, we show that they exhibit mono-affine scaling properties characterized by a roughness exponent ζ = 0.5 ± 0.05, which we explain theoretically from linear elastic fracture mechanics. Our findings support the description of the roughening process in two-dimensional brittle disordered solids by a random walk. Furthermore, they shed light on the failure mechanism at the origin of the persistent behavior with ζ ≈ 0.6-0.7 observed for fractures in other materials, suggesting a unified scenario for the geometry of cracks paths in two-dimensional disordered solids.

The initiation of frictional sliding between a flat-bottomed indenter and a planar single crystal substrate is analyzed using discrete dislocation plasticity. Plastic deformation is modeled through the motion of edge dislocations in an elastic solid with the lattice resistance to dislocation motion, dislocation nucleation, dislocation interaction with obstacles and dislocation annihilation incorporated through a set of constitutive rules. The adhesion between the indenter and the substrate is modeled using a shear traction versus sliding displacement cohesive relation. The evolution of the energy storage and dissipation are calculated as a function of contact size. (c) 2005 Elsevier B.V. All rights reserved.

We have recently proposed a nonlocal continuum crystal plasticity theory that is based on a statistical-mechanics description of the collective behaviour of dislocations. Kinetic equations for the dislocation density fields have been derived from the equation of motion of individual dislocations and have been coupled to a continuum description of single slip. Dislocation nucleation, the material resistance to dislocation glide and dislocation annihilation are included in the formulation. The theory is applied, in this paper, to the problem of bending of a single-crystal strip in plane strain, using parameter values obtained previously from fitting to discrete dislocation results of a different boundary value problem. A numerical solution of the problem is obtained using a finite element method. The bending moment versus rotation angle and the evolution of the dislocation structure are analysed for different orientations and specimen sizes with due consideration of the role of geometrically necessary dislocations. The results are compared to those of discrete dislocation simulations of the same problem. Without any additional fitting of the parameters, the continuum theory is able to describe the dependence on slip plane orientation and on specimen size.

Hydrogen attack is a material degradation process which involves partial dissolution of the microstructure in favor of the growth of methane-filled cavities. The various physical-chemical processes involved are strongly coupled. We present a numerical microstructural model for two of these processes, based on a variational approach. (C) 2002 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved.

Hydrogen attack is a material degradation process that occurs at elevated temperatures in hydrogen-rich environments, such as found in petrochemical installations. Weldments in components such as reactor vessels are particularly susceptible to hydrogen attack. This paper discusses a multi-scale micromechanics modelling approach in which the chemico-mechanical damage processes at sub-micron scale are coupled to the macroscopic behaviour through a series of size-scale transitions. A simulation of hydrogen attack in a welded reactor serves as an illustration of the approach. Copyright © 2001 John Wiley & Sons, Ltd.

Networks of cross-linked filamentous biopolymers form topological structures characterized by L, T and X cross-link types of connectivity 2, 3 and 4, respectively. The distribution of cross-links over these three types proofs to be very important for the initial elastic shear stiffness of isotropic rigidly cross-linked biopolymer networks. After proper scaling of this stiffness, we identify the topological function \(f(\mathcal{T} ) = ({l}_{\mathrm{c}}/\xi ){({n}_{\mathrm{X}}/{n}_{\mathrm{cl}})}^{2.5}\) that describes these effects in terms of the network parameters: mean section length l c, mesh size ξ and relative number of X cross-links n X ∕ n cl.

Two different approaches to intergranular crack propagation in brittle polycrystals are contrasted. Crack paths resulting from a method that allows a detailed description of the stress field within a polycrystal are compared to cracks dictated by topological considerations. In the first approach, a fracture path is determined with a Generalized Finite Element Method for polycrystals considering isotropic elastic grains. In the second approach a fracture path is generated using Dijkstra’s shortest path algorithm. This algorithm yields minimum fracture energy crack paths. A series of simulations is performed to assess the influence of the method of analysis on the crack path.

We study the mechanical stiffening behavior in two-dimensional (2D) cross-linked networks of semiflexible biopolymer filaments under simple shear. Filamental constituents immersed in a fluid undergo thermally excited bending motions. Pulling out these undulations results in an increase in the axial stiffness. We analyze this stiffening behavior of 2D semiflexible filaments in detail: we first investigate the average, {static} force-extension relation by considering the initially present undulated configuration that is pulled straight under a tensile force, and compare this result with the average response in which undulation dynamics is allowed during pulling, as derived earlier by MacKintosh and coworkers. We will show that the resulting mechanical behavior is rather similar, but with the axial stiffness being a factor 2 to 4 larger in the dynamic model. Furthermore, we study the stretching contribution in case of extensible filaments and show that, for 2D filaments, the mechanical response is dominated by {enthalpic} stretching. Based on the single-filament mechanics, we develop a 2D analytical model describing the mechanical behavior of biopolymer networks under simple shear, adopting the affine deformation assumption. These results are compared with discrete, finite-element (FE) calculations of a network consisting of semiflexible filaments. The FE calculations show that local, nonaffine filament reorientations occur that induce a transition from a bending-dominated response at small strains to a stretching-dominated response at larger strains. Stiffening in biopolymer networks thus results from a combination of stiffening in individual filaments and changes in the network topography.

Strain stiffening of protein networks is explored by means of a finite strain analysis of a two-dimensional network model of cross-linked semiflexible filaments. The results show that stiffening is caused by non-affine network rearrangements that govern a transition from a bending dominated response at small strains to a stretching dominated response at large strains. Thermally-induced filament undulations only have a minor effect; they merely postpone the transition., 5 pages, 5 figures

Strain stiffening of protein networks is explored by means of a finite strain analysis of a two-dimensional network model of cross-linked semiflexible filaments. The results show that stiffening is caused by non-affine network rearrangements that govern a transition from a bending dominated response at small strains to a stretching dominated response at large strains. Thermally-induced filament undulations only have a minor effect; they merely postpone the transition.

Although it is recognized that failure of glassy polymers involves crazing and shear yielding, most of the studies of their fracture account for one or the other mechanism. We present a finite element analysis in which crazing and shear yielding are incorporated. Shear yielding is accounted for through the description of a three-dimensional constitutive law of the bulk material, while crazing is modeled by a cohesive surface which comprises the three stages of initiation, thickening, and craze fibril breakdown and related crack formation. The description is able to capture the main features of glassy polymer fracture such as the ductile-to-brittle transition at low rates and the evolution of the toughness with loading rate. In particular, it is demonstrated that the competition between shear yielding and crazing governs the material’s toughness. Even if the description of crazing presented here is essentially phenomenological, a cohesive zone formulation is shown to provide a consistent formulation to bridge descriptions of failure at the molecular length scale with analyses performed at the continuum scale.

A two-dimensional nonlocal version of continuum crystal plasticity theory is proposed, which is based on a statistical-mechanics description of the collective behavior of dislocations coupled to standard small-strain crystal continuum kinematics for single slip. It involves a set of transport equations for the total dislocation density field and for the net-Burgers vector density field, which include a slip system back stress associated to the gradient of the net-Burgers vector density. The theory is applied to the problem of shearing of a two-dimensional composite material with elastic reinforcements in a crystalline matrix. The results are compared to those of discrete dislocation simulations of the same problem. The continuum theory is shown to be able to pick up the distinct dependence on the size of the reinforcing particles for one of the morphologies being studied. Also, its predictions are consistent with the discrete dislocation results during unloading, showing a pronounced Bauschinger effect. None of these features are captured by standard local plasticity theories. (C) 2003 Elsevier Ltd. All rights reserved.

Discrete dislocation simulations of thin films on semi-infinite substrates under cyclic thermal loading are presented. The thin film is modelled as a two-dimensional single crystal under plane strain conditions. Dislocations of edge character can be generated from initially present sources and glide in the film on a given set of slip systems. At each time step of the simulation, the stress field in the film is calculated through the solution of a boundary value problem, taking into account the long-range stress contribution of the current dislocation structure. The numerical results show a clear size effect in the plastic behaviour of two films with thicknesses of 0.25mum and 0.5mum. The mechanical response of the two films during the cyclic thermal loading is analysed, with an emphasis on the evolution of the dislocation structure.

Thermal stress evolution in polycrystalline thin films is analyzed using discrete dislocation plasticity. Stress develops in the film during cooling from a stress-free configuration due to the difference in thermal expansion coefficient between the film and its substrate. A plane strain formulation with only edge dislocations is used and each grain of the polycrystal has a specified set of slip systems. The film-substrate interface and the grain boundaries are impenetrable for the dislocations. Results are presented for two film thicknesses, with higher hardening seen for the thinner films.

Conventional continuum mechanics models of inelastic deformation processes axe size scale independent. In contrast, there is considerable experimental evidence that plastic flow in crystalline materials is size dependent over length scales of the order of tens of microns and smaller. At present there is no generally accepted framework for analyzing the size-dependent response of a plastically deforming crystal. Dislocation based plasticity can provide information on the form of the governing equations and the boundary conditions, as well as material properties. Solutions obtained using discrete dislocation plasticity and several recently proposed nonlocal continuum formulation are compared. The implications for modeling size dependent plasticity axe discussed.

Hydrogen attack is a material degradation process which involves partial dissolution of the microstructure in favor of the growth of methane filled cavities. Two numerical models are discussed to study this multi-physics process: a simple one-dimensional model and the start of a more sophisticated microstructural model solved by a finite element technique. The first model shows that hydrogen attack involves a strong coupling between dissolution and cavity growth. The more elaborate model will be used to assess the validity of the assumptions of the first model.

Growth islands due to large mismatch strain arising in Stranski-Krastanow (SK) and Volmer-Weber (VW) film growth can be used to produce large arrays of quantum dots. This same mismatch strain may also cause misfit dislocations to form, presenting a quality control problem. Johnson and Freund (J. Appl. Phys. 81(9), 1997, p6081) developed a two-dimensional model of misfit dislocation nucleation in SK and VW growth islands whereby they predict a power-law relation between misfit strain, epsilon(m), and the minimum island size to nucleate a misfit dislocation, R(c): R(c) proportional to epsilon(1/(lambda-1))(m) where lambda

A discrete dislocation simulation of plastic deformation in metallic interconnects caused by thermal stress is carried out. The calculations are carried out using a two dimensional plane strain formulation with only edge dislocations. A boundary value problem is formulated and solved for the evolution of the thermal stress field and the evolution of the dislocation structure in the cross-section of the line as cooling proceeds. For lines with a small cross section (height or width less than 1 mum), the local concentration of stresses due to dislocation patterning strongly affects the overall stress build up and relaxation. The results show a clear dependence of the transverse stress development on the line aspect ratio.

This paper concentrates on application of the so-called Discrete Dislocation Plasticity to high strain rate deformations. In particular the question is addressed if the DDP approach may capture the specific processes taking place at high strain rates. In particular the paper reports on tests of the validity of some approximations and provides some sample runs to show the applicability of the method. In assessing the results, one has to keep in mind two underpinning aspects: (1) the model is two-dimensional and (2) the results hold only in the regime where linear isotropic elasticity is valid. It was concluded that accelerations can not be neglected at very high strain rate deformations, both for the conventional and the relativistic case.

In this paper, shear deformation at high strain rates is modeled within the framework of discrete dislocation plasticity. The method of discrete dislocation plasticity is extended to incorporate the temperature rise induced by moving dislocations. Also, the stress and displacement fields of a screw dislocation on inclined planes in a periodic structure are developed. The influence on the temperature rise on various micro-mechanical processes is discussed.

In this paper, shear deformation at high strain rates is modelled with the framework of discrete dislocation plasticity. The total stress state is split into the stress state due to the dislocations in an infinite medium, and the complementary image stress, which is enforced by a finite element solution. Sources and obstacles are put into the material, and constitutive rules are implemented for the creation and annihilation of dislocations. High-velocity stress and displacement fields are used, as well as the Gillis-Gilman-Taylor drag relation. When the velocity of a dislocation approaches that of the local shear wave speed, the stress and displacement fields undergo a Lorentz-contraction in the direction of motion. The issue is addressed whether these local changes in stresses and displacements affect the overall stress-strain curves significantly. The dependence on temperature is briefly discussed.