Effects of Crystalline Anisotropy and Indenter Size on Nanoindentation by Multiscale Simulation

Nanoindentation processes in single crystal Ag thin film under different crystallographic orientations and various indenter widths are simulated by the quasicontinuum method. The nanoindentation deformation processes under influences of crystalline anisotropy and indenter size are investigated about hardness, load distribution, critical load for first dislocation emission and strain energy under the indenter. The simulation results are compared with previous experimental results and Rice-Thomson (R-T) dislocation model solution. It is shown that entirely different dislocation activities are presented under the effect of crystalline anisotropy during nanoindentation. The sharp load drops in the load–displacement curves are caused by the different dislocation activities. Both crystalline anisotropy and indenter size are found to have distinct effect on hardness, contact stress distribution, critical load for first dislocation emission and strain energy under the indenter. The above quantities are decreased at the indenter into Ag thin film along the crystal orientation with more favorable slip directions that easy trigger slip systems; whereas those will increase at the indenter into Ag thin film along the crystal orientation with less or without favorable slip directions that hard trigger slip systems. The results are shown to be in good agreement with experimental results and R-T dislocation model solution

The individual environment, not the family is the most important influence on preferences for common non-alcoholic beverages in adolescence

Beverage preferences are an important driver of consumption, and strong liking for beverages high in energy (e.g. sugar-sweetened beverages [SSBs]) and dislike for beverages low in energy (e.g. non-nutritive sweetened beverages [NNSBs]) are potentially modifiable risk factors contributing to variation in intake. Twin studies have established that both genes and environment play important roles in shaping food preferences; but the aetiology of variation in non-alcoholic beverage preferences is unknown. 2865 adolescent twins (18–19-years old) from the Twins Early Development Study were used to quantify genetic and environmental influence on variation in liking for seven non-alcoholic beverages: SSBs; NNSBs; fruit cordials, orange juice, milk, coffee, and tea. Maximum Likelihood Structural Equation Modelling established that beverage preferences have a moderate to low genetic basis; from 18% (95% CI: 10%, 25%) for orange juice to 42% (36%, 43%) for fruit cordials. Aspects of the environment that are not shared by twin pairs explained all remaining variance in drink preferences. The sizeable unique environmental influence on beverage preferences highlights the potential for environmental modification. Policies and guidelines to change preferences for unhealthy beverages may therefore be best directed at the wider environment

In silico assessment of biomedical products: the conundrum of rare but not so rare events in two case studies

In silico clinical trials, defined as “The use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention,” have been proposed as a possible strategy to reduce the regulatory costs of innovation and the time to market for biomedical products. We review some of the the literature on this topic, focusing in particular on those applications where the current practice is recognized as inadequate, as for example, the detection of unexpected severe adverse events too rare to be detected in a clinical trial, but still likely enough to be of concern. We then describe with more details two case studies, two successful applications of in silico clinical trial approaches, one relative to the University of Virginia/Padova simulator that the Food and Drug Administration has accepted as possible replacement for animal testing in the preclinical assessment of artificial pancreas technologies, and the second, an investigation of the probability of cardiac lead fracture, where a Bayesian network was used to combine in vivo and in silico observations, suggesting a whole new strategy of in silico-augmented clinical trials, to be used to increase the numerosity where recruitment is impossible, or to explore patients’ phenotypes that are unlikely to appear in the trial cohort, but are still frequent enough to be of concern

The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity

Deregulated metabolism is a well-established hallmark of cancer. At the hub of various metabolic pathways deeply integrated within mitochondrial functions, the α-ketoglutarate dehydrogenase complex represents a major modulator of electron transport chain activity and tricarboxylic acid cycle (TCA) flux, and is a pivotal enzyme in the metabolic reprogramming following a cancer cell’s change in bioenergetic requirements. By contributing to the control of α-ketoglutarate levels, dynamics, and oxidation state, the α-ketoglutarate dehydrogenase is also essential in modulating the epigenetic landscape of cancer cells. In this review, we will discuss the manifold roles that this TCA enzyme and its substrate play in cancer

Achilles tendon stress is more sensitive to subject-specific geometry than subject-specific material properties: A finite element analysis

Abstract This study used subject-specific measures of three-dimensional (3D) free Achilles tendon geometry in conjunction with a finite element method to investigate the effect of variation in subject-specific geometry and subject-specific material properties on tendon stress during submaximal isometric loading. Achilles tendons of eight participants (Aged 25–35 years) were scanned with freehand 3D ultrasound at rest and during a 70% maximum voluntary isometric contraction. Ultrasound images were segmented, volume rendered and transformed into subject-specific 3D finite element meshes. The mean (±SD) lengths, volumes and cross-sectional areas of the tendons at rest were 62 ± 13 mm, 3617 ± 984 mm3 and 58 ± 11 mm2 respectively. The measured tendon strain at 70% MVIC was 5.9 ± 1.3%. Subject-specific material properties were obtained using an optimisation approach that minimised the difference between measured and modelled longitudinal free tendon strain. Generic geometry was represented by the average mesh and generic material properties were taken from the literature. Local stresses were subsequently computed for combinations of subject-specific and generic geometry and material properties. For a given geometry, changing from generic to subject-specific material properties had little effect on the stress distribution in the tendon. In contrast, changing from generic to subject-specific geometry had a 26-fold greater effect on tendon stress distribution. Overall, these findings indicate that the stress distribution experienced by the living free Achilles tendon of a young and healthy population during voluntary loading are more sensitive to variation in tendon geometry than variation in tendon material properties

Influence of altered geometry and material properties on tissue stress distribution under load in tendinopathic Achilles tendons – A subject-specific finite element analysis

Obst, SJ ORCiD: 0000-0003-4299-9628Achilles tendon material properties and geometry are altered in Achilles tendinopathy. The purpose of this study was to determine the relative contributions of altered material properties and geometry to free Achilles tendon stress distribution during a sub-maximal contraction in tendinopathic relative to healthy tendons. Tendinopathic (n = 8) and healthy tendons (n = 8) were imaged at rest and during a sub-maximal voluntary isometric contraction using three-dimensional freehand ultrasound. Images were manually segmented and used to create subject-specific finite element models. The resting cross-sectional area of the free tendon was on average 31% greater for the tendinopathic compared to healthy tendons. Material properties for each tendon were determined using a numerical parameter optimisation approach that minimised the difference in experimentally measured longitudinal strain and the strain predicted by the finite element model under submaximal loading conditions for each tendon. The mean Young's modulus for tendinopathic tendons was 53% lower than the corresponding control value. Finite element analyses revealed that tendinopathic tendons experience 24% less stress under the same submaximal external loading conditions compared to healthy tendons. The lower tendon stress in tendinopathy was due to a greater influence of tendon cross-sectional area, which alone reduced tendon stress by 30%, compared to a lower Young's modulus, which alone increased tendon stress by 8%. These findings suggest that the greater tendon cross-sectional area observed in tendinopathy compensates for the substantially lower Young's modulus, thereby protecting pathological tendon against excessive stress. © 201

Achilles tendon stress is more sensitive to subject-specific geometry than subject-specific material properties: A finite element analysis

Abstract This study used subject-specific measures of three-dimensional (3D) free Achilles tendon geometry in conjunction with a finite element method to investigate the effect of variation in subject-specific geometry and subject-specific material properties on tendon stress during submaximal isometric loading. Achilles tendons of eight participants (Aged 25–35 years) were scanned with freehand 3D ultrasound at rest and during a 70% maximum voluntary isometric contraction. Ultrasound images were segmented, volume rendered and transformed into subject-specific 3D finite element meshes. The mean (±SD) lengths, volumes and cross-sectional areas of the tendons at rest were 62 ± 13 mm, 3617 ± 984 mm3 and 58 ± 11 mm2 respectively. The measured tendon strain at 70% MVIC was 5.9 ± 1.3%. Subject-specific material properties were obtained using an optimisation approach that minimised the difference between measured and modelled longitudinal free tendon strain. Generic geometry was represented by the average mesh and generic material properties were taken from the literature. Local stresses were subsequently computed for combinations of subject-specific and generic geometry and material properties. For a given geometry, changing from generic to subject-specific material properties had little effect on the stress distribution in the tendon. In contrast, changing from generic to subject-specific geometry had a 26-fold greater effect on tendon stress distribution. Overall, these findings indicate that the stress distribution experienced by the living free Achilles tendon of a young and healthy population during voluntary loading are more sensitive to variation in tendon geometry than variation in tendon material properties