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Prosthetic foot stiffness, which is typically invariable for commercially available prosthetic feet, needs to be considered when prescribing a prosthetic foot. While a biological foot adapts its function according to the movement task, an individual with lower limb amputation may be limited during more functionally demanding gait tasks by their conventional energy storing and return prosthetic foot. How do changes in prosthetic foot stiffness during incline walking affect biomechanical measures as well as perception of participants. Kinetic and kinematic data were collected during incline walking, for five participants with trans-tibial amputation. A mixed model analysis of variance was used to analyse the effects of changing the stiffness during incline walking, using a novel variable-stiffness unit built on a commercially available prosthetic foot. Biomechanical results were also analysed on an individual level alongside the participant feedback, for a better understanding of the various strategies and perceptions exhibited during incline walking. Statistically significant effects were only observed on the biomechanical parameters directly related to prosthetic ankle kinematics and kinetics (i.e., peak prosthetic ankle dorsiflexion, peak prosthetic ankle power, dynamic joint stiffness during controlled dorsiflexion). Participant perception during walking was affected by changes in stiffness. Individual analyses revealed varied perceptions and varied biomechanical responses among participants. While changes in prosthesis mechanical properties influenced the amputee's experience, minimal immediate effects were found with the overall gait pattern. The reported inter-participant variability may be due to the person's physical characteristics or habitual gait pattern, which may influence prosthesis function. The ability to vary prosthetic foot stiffness during the assessment phase of setting up a prosthesis could provide useful information to guide selection of the appropriate prosthetic device for acceptable performance across a range of activities. • Individuals exhibit different gait patterns which may influence prosthetic preference. • Variability in prosthetic foot stiffness perception and preference was reported. • Providing an option of varying stiffness during different gait tasks may benefit the user. [ABSTRACT FROM AUTHOR]

The direct use of industrial flue gas in microalgae production is desired for mitigating CO 2 emissions, but the low pH resulting from the inflow of acidic gases (mainly CO 2 , NO x, and SO x) imposes detrimental effects on microalgal growth and is considered the main technical challenge for simultaneous biomass production and CO 2 sequestration. In this study, we investigated the adaptive responses of the model marine diatom Phaeodactylum tricornutum to acidic stress at pH 6.0. Gradual changes in the ratio of morphotypes, chlorophyll content, and photosynthetic efficiency were observed as a result of adaptive laboratory evolution (ALE) under constant acidic stress. The evolved strains showed a significant increase in growth rate in acidic conditions after ALE, and phenotypic characterization demonstrated a stable trait of acid tolerance with an average increase in growth by 110.4%, 46.1%, and 27.5% at pH 5.5, 6.0, and 6.5, respectively compared with the parental wild-type strain. Furthermore, RNA sequencing and whole-genome re-sequencing analyses revealed that core pathways, including photosynthesis, pH regulation/ion transport, and carbohydrate and fatty acid metabolism, were upregulated across all three evolved strains, though they exhibited different evolutionary trajectories. This study demonstrated the feasibility of recovering photosynthetic capability after acidic stress in the marine diatom P. tricornutum through ALE and provided molecular data to reveal essential alterations in genetic regulations that could enable cells to tolerate low environmental pH. [Display omitted] • Acidic pH significantly impaired the photosynthesis and growth of P. tricornutum. • Low-pH tolerance in P. tricornutum was improved through the adaptive laboratory evolution process. • Photosynthesis, pH regulation/ion transport, carbohydrate and fatty acid metabolism were upregulated in acid-adapted diatoms. • Whole genome resequencing showed distinct evolutionary trajectories among the evolved strains. [ABSTRACT FROM AUTHOR]

Acute Respiratory Distress Syndrome (ARDS) is a condition that endangers the lives of many Intensive Care Unit patients through gradual reduction of lung function. Due to its heterogeneity, this condition has been difficult to diagnose and treat, although it has been the subject of continuous research, leading to the development of several tools for modeling disease progression on the one hand, and guidelines for diagnosis on the other, mainly the "Berlin Definition". This paper describes the development of a deep learning-based surrogate model of one such tool for modeling ARDS onset in a virtual patient: the Nottingham Physiology Simulator. The model-development process takes advantage of current machine learning and data-analysis techniques, as well as efficient hyperparameter-tuning methods, within a high-performance computing-enabled data science platform. The lightweight models developed through this process present comparable accuracy to the original simulator (per-parameter R2 > 0.90). The experimental process described herein serves as a proof of concept for the rapid development and dissemination of specialised diagnosis support systems based on pre-existing generalised mechanistic models, making use of supercomputing infrastructure for the development and testing processes and supported by open-source software for streamlined implementation in clinical routines. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic shed light on the need for quick diagnosis tools in healthcare, leading to the development of several algorithmic models for disease detection. Though these models are relatively easy to build, their training requires a lot of data, storage, and resources, which may not be available for use by medical institutions or could be beyond the skillset of the people who most need these tools. This paper describes a data analysis and machine learning platform that takes advantage of high-performance computing infrastructure for medical diagnosis support applications. This platform is validated by re-training a previously published deep learning model (COVID-Net) on new data, where it is shown that the performance of the model is improved through large-scale hyperparameter optimisation that uncovered optimal training parameter combinations. The per-class accuracy of the model, especially for COVID-19 and pneumonia, is higher when using the tuned hyperparameters (healthy: 96.5%; pneumonia: 61.5%; COVID-19: 78.9%) as opposed to parameters chosen through traditional methods (healthy: 93.6%; pneumonia: 46.1%; COVID-19: 76.3%). Furthermore, training speed-up analysis shows a major decrease in training time as resources increase, from 207 min using 1 node to 54 min when distributed over 32 nodes, but highlights the presence of a cut-off point where the communication overhead begins to affect performance. The developed platform is intended to provide the medical field with a technical environment for developing novel portable artificial-intelligence-based tools for diagnosis support. [ABSTRACT FROM AUTHOR]

As a major primary producer in marine environments, diatoms have been considered as promising feedstocks for their applications in functional foods, bioactive pharmaceuticals, and cosmetics. This review focuses on the biotechnology potential of diatoms for value-added products like carotenoids. The impact of abiotic environmental stresses, such as intensity and quality of incident light, nutrient deficiency and silicon depletion, on diatoms has been examined to determine key factors that affect the growth performance and the accumulation of valuable compounds. Previous studies suggested that adaptive evolution could be an efficient method to improve the diatom productivity of valuable compounds. Light emitting diode (LED)-based photobioreactors were introduced and proposed as a promising new technology for producing quality products from diatoms. Currently available molecular biology tools were also summarized and discussed in relation to their application in the production of carotenoids and other valuable products. Taken together, systems biology and synthetic biology approaches have the potential to address the challenges faced while working toward the industrial application of diatoms. [ABSTRACT FROM AUTHOR]

Recently, gravity-driven membrane (GDM) filtration has been adopted as an alternative solution for decentralized wastewater treatment due to easy installation and maintenance, reduced energy and operation cost, and low global warming impact. This study investigated the influence of microplastic size (0.5–0.8 μm and 40–48 μm) and amount (0.1 and 0.2 g/L) on the membrane performance and microbial community in GDM systems for primary municipal wastewater treatment. The results showed that dosing microplastics in the GDM systems led to 9–54% lower permeate flux than that in the control. This was attributed to more cake formation (up to 6.4-fold) with more deposition of extracellular polymeric substances (EPS, up to 1.5-fold) and divalent cations (up to 2.1-fold) in the presence of microplastics, especially with increasing microplastic amount or size. However, the dosed microplastics promoted formation of heterogeneous cake layers with more porous nature, possibly because microplastics created void space in the cake and also tended to bind with divalent cations to reduce EPS-divalent cations interactions. In the biofilm of the GDM systems, the presence of microplastics could lower the number of total species, but it greatly enhanced the abundance of certain dominant prokaryotes (Phenylobacterium haematophilum , Planctomycetota bacterium , and Flavobacteriales bacterium), eukaryotes (Stylonychia lemnae , Halteria grandinella , and Paramicrosporidium saccamoebae) , and virus (phylum Nucleocytoviricota), as well as amino acid and lipid metabolic functions. Especially, the small-size microplastics at a higher dosed amount led to more variations of microbial community structure and microbial metabolic functions. [Display omitted] • GDM systems with MPs produced permeate with less biodegradable organics. • MPs in GDM systems led to lower fluxes by enhanced cake formation. • Increasing microplastic size or amount led to more porous cake on membranes. • MPs impacted microbial community structure and metabolic functions of biofilm layer. • Small-size microplastics led to more variations of microbial species and functions. [ABSTRACT FROM AUTHOR]

Adaptation of lower limb function to different gait tasks is inherently not as effective among individuals with lower limb amputation as compared to able-bodied individuals. Varying stiffness of a prosthetic foot may be a way of facilitating gait tasks that require larger ankle joint range of motion. Three stiffness settings of a novel prosthetic foot design were tested for level walking at three speeds as well as for 7,5° incline and decline walking. Outcome measures, describing ankle range of motion and ankle dynamic joint stiffness were contrasted across the three stiffness settings. Standardized mechanical tests were done for the hindfoot and forefoot. Dorsiflexion angle was incrementally increased with a softer foot and a faster walking speed / higher degree of slope. The concurrent dynamic joint stiffness exhibited a less systematic change, especially during INCLINE and DECLINE walking. The small difference seen between the stiffness settings for hindfoot loading limits analysis for the effects of stiffness during weight acceptance, however, a stiffer foot significantly restricted plantarflexion during DECLINE. Varying stiffness settings within a prosthetic foot does have an effect on prosthetic foot dynamics, and differences are task dependent, specifically in parameters involving kinetic attributes. When considering the need for increased ankle range of motion while performing more demanding gait tasks, a foot that allows the users themselves to adjust stiffness according to the task at hand may be of benefit for active individuals, possibly enhancing the user's satisfaction and comfort during various daily activities. • Three stiffness settings were analyzed with a novel prosthetic foot design. • Dynamic Joint Stiffness can provide insight into a prosthetic foot's dynamics. • Prosthetic foot dynamics and characteristics during gait are task dependent. • Mechanical data does not capture the prosthetic foot's dynamics across gait tasks. • Studies of long-term effects of stiffness change and users´ preferences are needed. [ABSTRACT FROM AUTHOR]

Abstract To convert waste CO 2 from flue gases of power plants into value-added products, bio-mitigation technologies show promise. In this study, we cultivated a fast-growing species of green microalgae, Chlorella vulgaris , in different sizes of photobioreactors (PBRs) and developed a strategy using small doses of sugars for enhancing CO 2 sequestration under light-emitting diode illumination. Glucose supplementation at low levels resulted in an increase of photoautotrophic growth-driven biomass generation as well as CO 2 capture by 10% and its enhancement corresponded to an increase of supplied photon flux. The utilization of urea instead of nitrate as the sole nitrogen source increased photoautotrophic growth by 14%, but change of nitrogen source didn't compromise glucose-induced enhancement of photoautotrophic growth. The optimized biomass productivity achieved was 30.4% higher than the initial productivity of purely photoautotrophic culture. The major pigments in the obtained algal biomass were found comparable to its photoautotrophic counterpart and a high neutral lipids productivity of 516.6 mg/(L·day) was achieved after optimization. A techno-economic model was also developed, indicating that LED-based PBRs represent a feasible strategy for converting CO 2 into value-added algal biomass. Graphical abstract Unlabelled Image Highlights • Fine-tuning mixotrophic culture of microalgae enhances CO 2 bio-fixation. • CO 2 capture in sugar-stimulated algal culture enhanced with increased light supply. • Sugar-stimulated algae have as much pigments as its photoautotrophic counterpart. • A techno-economic model evaluates the feasibility of large-scale algae cultivation. [ABSTRACT FROM AUTHOR]

The temperature dependence of biological processes has been studied at the levels of individual biochemical reactions and organism physiology (e.g. basal metabolic rates) but has not been examined at the metabolic network level. Here, we used a systems biology approach to characterize the temperature dependence of the human red blood cell (RBC) metabolic network between 4 and 37 °C through absolutely quantified exo-and endometabolomics data. We used an Arrhenius-type model (Q10) to describe how the rate of a biochemical process changes with every 10 °C change in temperature. Multivariate statistical analysis of the metabolomics data revealed that the same metabolic network-level trends previously reported for RBCs at 4 °C were conserved but accelerated with increasing temperature. We calculated a median Q10 coefficient of 2.89 ± 1.03, within the expected range of 2-3 for biological processes, for 48 individual metabolite concentrations. We then integrated these metabolomics measurements into a cell-scale metabolic model to study pathway usage, calculating a median Q10 coefficient of 2.73 ± 0.75 for 35 reaction fluxes. The relative fluxes through glycolysis and nucleotide metabolism pathways were consistent across the studied temperature range despite the non-uniform distributions of Q10 coefficients of individual metabolites and reaction fluxes. Together, these results indicate that the rate of change of network-level responses to temperature differences in RBC metabolism is consistent between 4 and 37 °C. More broadly, we provide a baseline characterization of a biochemical network given no transcriptional or iotranslational regulation that can be used to explore the temperature dependence of metabolism. [ABSTRACT FROM AUTHOR]

Background: Alternate sugar metabolism during red blood cell (RBC) storage is not well understood. Here we report fructose and mannose metabolism in RBCs during cold storage in SAGM and the impact that these monosaccharides have on metabolic biomarkers of RBC storage lesion.Study Design and Methods: RBCs were stored in SAGM containing uniformly labeled 13 C-fructose or 13 C-mannose at 9 or 18 mmol/L concentration for 25 days. RBCs and media were sampled at 14 time points during storage and analyzed using ultraperformance liquid chromatography-mass spectrometry. Blood banking quality assurance measurements were performed.Results: Red blood cells incorporated fructose and mannose during cold storage in the presence of glucose. Mannose was metabolized in preference to glucose via glycolysis. Fructose lowered adenosine triphosphate (ATP) levels and contributed little to ATP maintenance when added to SAGM. Both monosaccharides form the advanced glycation end product glycerate. Mannose activates enzymes in the RBC that take part in glycan synthesis.Conclusions: Fructose or mannose addition to RBC SAGM concentrates may not offset the shift in metabolism of RBCs that occurs after 10 days of storage. Fructose and mannose metabolism at 4°C in SAGM reflects their metabolism at physiologic temperature. Glycerate excretion is a measure of protein deglycosylation activity in stored RBCs. No cytoprotective effect was observed upon the addition of either fructose or mannose to SAGM. [ABSTRACT FROM AUTHOR]

[Display omitted] • Initial intermediate pore blocking, followed by cake filtration was noticed in GDM systems. • Cake filtration displayed its dominance during constant flux filtration of wastewater. • Ultrasonication facilitated reducing both cake fouling and specific cake resistance. • Effectiveness of ultrasonication in fouling control was related to cake morphology. • Ceramic-based GDM is economically feasible for household application. This study investigated the feasibility of using ultrasonication as a ceramic microfiltration membrane fouling control strategy during gravity-driven membrane (GDM) filtration and constant flux filtration of primary municipal wastewater. The fouling model fitting curves revealed that initial intermediate pore blocking was dominant in the GDM system, followed by cake filtration; while cake filtration was dominant during constant flux filtration with a continuously increasing pattern. In the GDM system, periodic ultrasonication cleaning achieved higher cake resistance reduction (∼60 % vs ∼ 26 %) and led to lower specific cake resistances (0.2–2.0 × 107 vs 29.6–59.3 × 107 m/mg) compared to periodic backwash. Ultrasonication-facilitated fouling mitigation effectiveness was related to cake properties (such as cake foulant density and porosity) and improved with extending ultrasonication duration. The foulant examination indicated that ultrasonication may result in porous cake nature by cake expansion and facilitate detaching particulate foulants and soluble organics (such as biopolymers) from the membrane. Cost analysis revealed that with commercial ceramic membranes, ultrasonication-facilitated GDM systems are economically feasible for treating wastewater at a household scale (∼1.1 EUR/m3 water), while ultrasonication-facilitated constant flux filtration systems are favorable at a small-community scale (∼0.5 EUR/m3 water). Furthermore, it was predicted that the use of low-cost recycled ceramic membranes would allow GDM systems as economical decentralized wastewater treatment processes due to their lower water production cost (∼0.16 EUR/m3 water) with easy operation and maintenance. [ABSTRACT FROM AUTHOR]

BACKGROUND: Platelet concentrates (PCs) can be prepared using three methods: platelet (PLT)-rich plasma, apheresis, and buffy coat. The aim of this study was to obtain a comprehensive data set that describes metabolism of buffy coat-derived PLTs during storage and to compare it with a previously published parallel data set obtained for apheresis-derived PLTs. STUDY DESIGN AND METHODS: During storage we measured more than 150 variables in 8 PLT units, prepared by the buffy coat method. Samples were collected at seven different time points resulting in a data set containing more than 8000 measurements. This data set was obtained by combining a series of standard quality control assays to monitor the quality of stored PLTs and a deep coverage metabolomics study using liquid chromatography coupled with mass spectrometry. RESULTS: Stored PLTs showed a distinct metabolic transition occurring 4 days after their collection. The transition was evident in PLT produced by both production methods. Apheresis-derived PLTs showed a clearer phenotype of PLT activation during early days of storage. The activated phenotype of apheresis PLTs was accompanied by a higher metabolic activity, especially related to glycolysis and the tricarboxylic acid cycle. Moreover, the extent of the activation differed between bags resulting in interbag variability in the storage lesion of apheresis-prepared PLTs. This may be related to donor-related polymorphism. CONCLUSION: This study demonstrated two discrete metabolic phenotypes in stored PLTs prepared with both apheresis and buffy coat methods. PLT activation occurs during the first metabolic phenotype and might lead to a low reproducibility of the apheresis PCs. [ABSTRACT FROM AUTHOR]

Background Platelet ( PLT) concentrates are routinely stored for 5 to 7 days. During storage they exhibit what has been termed PLT storage lesion ( PSL), which is evident by a loss of hemostatic function when transfused into patients. The overall goal of this study was to obtain a comprehensive data set describing PLT metabolism during storage. Study Design and Methods The experimental approach adopted to achieve this goal combined a series of standard assays to monitor the quality of stored PLTs and a deep-coverage metabolomics study using liquid chromatography coupled with mass spectrometry performed on both the extracellular and the intracellular environments. During storage we measured 174 different variables in 6 PLT units, collected by apheresis. Samples were collected at eight different time points resulting in a data set containing more than 8000 measurements. Results Stored PLTs did not undergo a monotonic decay, but experienced systematic changes in metabolism reflected in three discrete metabolic phenotypes: The first ( Days 0-3) was associated with active glycolysis, pentose phosphate pathway, and glutathione metabolism and down regulation of tricarboxylic acid ( TCA) cycle. The second ( Days 4-6) was associated with a more active TCA cycle as well as increased purine metabolism. A third metabolic phenotype of less clinical relevance ( Days 7-10) was associated with a faster decay of cellular metabolism. Conclusion PSL is not associated with a linear decay of metabolism, but rather with successive metabolic shifts. These findings may give new insight into the mechanisms underlying PSL and encourage the deployment of systems biology methods to PSL. [ABSTRACT FROM AUTHOR]

Motivation: A genome-scale reconstruction of human metabolism, Recon 2, is available but no interface exists to interactively visualize its content integrated with omics data and simulation results. Results: We manually drew a comprehensive map, ReconMap 2.0, that is consistent with the content of Recon 2. We present it within a web interface that allows content query, visualization of custom datasets and submission of feedback to manual curators. [ABSTRACT FROM AUTHOR]

Background Recent years have witnessed a rising trend in exploring microalgae for valuable carotenoid products as the demand for lutein and many other carotenoids in global markets has increased significantly. In green microalgae lutein is a major carotenoid protecting cellular components from damage incurred by reactive oxygen species under stress conditions. In this study, we investigated the effects of abiotic stressors on lutein accumulation in a strain of the marine microalga D. salina which had been selected for growth under stress conditions of combined blue and red lights by adaptive laboratory evolution. Results Nitrate concentration, salinity and light quality were selected as three representative influencing factors and their impact on lutein production in batch cultures of D. salina was evaluated using response surface analysis. D. salina was found to be more tolerant to hyperosmotic stress than to hypo-osmotic stress which caused serious cell damage and death in a high proportion of cells while hyper-osmotic stress increased the average cell size of D. salina only slightly. Two models were developed to explain how lutein productivity depends on the stress factors and for predicting the optimal conditions for lutein productivity. Among the three stress variables for lutein production, stronger interactions were found between nitrate concentration and salinity than between light quality and the other two. The predicted optimal conditions for lutein production were close to the original conditions used for adaptive evolution of D. salina. This suggests that the conditions imposed during adaptive evolution may have selected for the growth optima arrived at. Conclusions This study shows that systematic evaluation of the relationship between abiotic environmental stresses and lutein biosynthesis can help to decipher the key parameters in obtaining high levels of lutein productivity in D. salina. This study may benefit future stress-driven adaptive laboratory evolution experiments and a strategy of applying stress in a stepwise manner can be suggested for a rational design of experiments. [ABSTRACT FROM AUTHOR]

There is a particularly high interest to derive carotenoids such as β-carotene and lutein from higher plants and algae for the global market. It is well known that β-carotene can be overproduced in the green microalga Dunaliella salina in response to stressful light conditions. However, little is known about the effects of light quality on carotenoid metabolism, e.g., narrow spectrum red light. In this study, we present UPLC-UV-MS data from D. salina consistent with the pathway proposed for carotenoid metabolism in the green microalga Chlamydomonas reinhardtii. We have studied the effect of red light-emitting diode (LED) lighting on growth rate and biomass yield and identified the optimal photon flux for D. salina growth. We found that the major carotenoids changed in parallel to the chlorophyll b content and that red light photon stress alone at high level was not capable of upregulating carotenoid accumulation presumably due to serious photodamage. We have found that combining red LED (75 %) with blue LED (25 %) allowed growth at a higher total photon flux. Additional blue light instead of red light led to increased β-carotene and lutein accumulation, and the application of long-term iterative stress (adaptive laboratory evolution) yielded strains of D. salina with increased accumulation of carotenoids under combined blue and red light. [ABSTRACT FROM AUTHOR]

Abstract: Pushout tests can be used to estimate the shear strength of the bone implant interface. Numerous such experimental studies have been published in the literature. Despite this researchers are still some way off with respect to the development of accurate numerical models to simulate implant stability. In the present work a specific experimental pushout study from the literature was simulated using two different bones implant interface models. The implant was a porous coated Ti–6Al–4V retrieved 4 weeks postoperatively from a dog model. The purpose was to find out which of the interface models could replicate the experimental results using physically meaningful input parameters. The results showed that a model based on partial bone ingrowth (ingrowth stability) is superior to an interface model based on friction and prestressing due to press fit (initial stability). Even though the present study is limited to a single experimental setup, the authors suggest that the presented methodology can be used to investigate implant stability from other experimental pushout models. This would eventually enhance the much needed understanding of the mechanical response of the bone implant interface and help to quantify how implant stability evolves with time. [Copyright &y& Elsevier]

Abstract: The aim of the present study is to compare the results from subject-specific finite element analysis (FEA) of a human femur to experimental measurements, using two different methods for assigning material properties to the FE models. A modified material mapping strategy allowing for spatial variation of material properties within the elements and Young''s modulus surface corrections is presented and compared to a more conventional strategy, whereby constant material properties are assigned to each element. The accuracy of the superficial stress–strain predictions was evaluated against experimental results from 13 strain gauges and five different load cases. Both methods predicted stresses with acceptable accuracy (R 2 =0.92, root mean square error, RMSE<10%), with the conventional method performing slightly better. The modified method performed better in strain prediction (R 2 =0.85, RMSE=23% versus R 2 =0.79, RMSE=31%). [Copyright &y& Elsevier]

Abstract: Background: In many published studies, elastic properties of bone are correlated to the bone density, in order to derive an empirical elasticity–density relationship. The most common use of these relationships is the prediction of the bone local properties from medical imaging data in subject-specific numerical simulation studies. The proposed relationships are substantially different one from the other. It is unclear whether such differences in elasticity–density relationships can be entirely explained in terms of methodological discrepancies among studies. Methods: All relevant literature was reviewed. Only elasticity–density relationships derived from similarly controlled experiments were included and properly normalized. The resulting relationships were grouped according to the most important methodological differences: type of end support during testing, specimen geometry, and anatomical sampling location. Findings: Even after normalization with respect to strain rate and densitometric measurement unit, substantial inter-study differences do exist, and they can only be partially explained by the methodological differences between studies. Interpretation: Some recommendations are made for the application of elasticity–density relationships to subject-specific finite element studies. The importance of defining a standardized mechanical testing methodology for bone specimens is stressed, and some guidelines that emerged from the literature are proposed. To identify density–elasticity relationships suitable for use in subject-specific FE studies, the development of a benchmark study is also proposed, where the elasticity–density relationship is taken as the variable under study, and a numerical model of known numerical accuracy predicts experimental strain measurements. [Copyright &y& Elsevier]