Validation of homogenized finite element models of human metastatic vertebrae using digital volume correlation

The incidence of vertebral fragility fracture is increased by the presence of preexisting pathologies such as metastatic disease. Computational tools could support the fracture prediction and consequently the decision of the best medical treatment. Anyway, validation is required to use these tools in clinical practice. To address this necessity, in this study subject-specific homogenized finite element models of single vertebrae were generated from micro CT images for both healthy and metastatic vertebrae and validated against experimental data. More in detail, spine segments were tested under compression and imaged with micro CT. The displacements field could be extracted for each vertebra singularly using the digital volume correlation full-field technique. Homogenized finite element models of each vertebra could hence be built from the micro CT images, applying boundary conditions consistent with the experimental displacements at the endplates. Numerical and experimental displacements and strains fields were eventually compared. In addition, the outcomes of a micro CT based homogenized model were compared to the ones of a clinical-CT based model. Good agreement between experimental and computational displacement fields, both for healthy and metastatic vertebrae, was found. Comparison between micro CT based and clinical-CT based outcomes showed strong correlations. Furthermore, models were able to qualitatively identify the regions which experimentally showed the highest strain concentration. In conclusion, the combination of experimental full-field technique and the in-silico modelling allowed the development of a promising pipeline for validation of fracture risk predictors, although further improvements in both fields are needed to better analyse quantitatively the post-yield behaviour of the vertebra

Multi-vertebral CT-based FE models implementing linear isotropic population-based material properties for the intervertebral discs cannot accurately predict strains

Vertebral fractures prediction in clinics lacks of accuracy. The most used scores have limitations in distinguishing between subjects at risk or not. Finite element (FE) models generated from computed tomography (CT) of these patients may improve the predictive capability. Many models have already been proposed but the most of them considered the single vertebral body, excluding from the analysis the role of the inter-vertebral discs in the distribution of the load through the spine. Multi-vertebral models instead allow to examine more complex boundary condition. However, CT scans do not provide subject-specif information about the material properties of the disc. Consequently, the goal of the study was to validate a multi-vertebral FE model with subject specific modelling of the vertebral bone and population-based properties assigned to the disc, idealizing them with a linear isotropic material. Boundary condition were assigned in order to reproduce an experimental test performed on the same specimen and recorded using digital image correlation technique (DIC). FE and DIC strains on the vertebral surfaces are compared point-wise. Young's modulus values in the range 25-30 MPa allowed to achieve a comparable order of magnitude between experimental and computational data. However, the two distribution remained strongly different. To conclude, subject-specific material properties need to be assigned also to the discs as well as to the vertebrae to achieve acceptable accuracy in the assessment of the fracture risk.Comment: 18 pages, 6 figures submitted to Biomechanics and Modeling in Mechanobiolog

The protein environment restricts the intramolecular charge transfer character of the luciferine/luciferase complex

The electronic characterization of the luciferine/luciferase complex is fundamental to tune its photophysical properties and develop more efficient devices based on this luminiscent system. Here, we apply molecular dynamics simulations, hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and transition density analysis to compute the absorption and emission spectra of luciferine/luciferase and analyze the nature of the relevant electronic state and its behaviour with the intramolecular and intermolecular degrees of freedom. It is found that the torsional motion of the chromophore is hampered by the presence of the enzyme, reducing the intramolecular charge transfer nature of the absorbing and emitting state. In addition, such a reduced charge transfer character does not correlate in a strong way neither with the intramolecular motion of the chromophore nor with the chromophore/amino-acid distances. However, the presence of a polar environment around the oxygen atom of the thiazole ring of the oxyluciferin, coming from both the protein and the solvent, enhances the charge transfer character of the emitting stateWe thank the support of the Spanish Ministry of Science and Innovation through the project PID2020-117806GA-I00 funded by MCIN/AEI/10.13039/501100011033, the Comunidad de Madrid through the Attraction of Talent Program (Grant ref 2018-T1/ BMD-10261) and the Universidad Autónoma de Madrid through the Ayudas para el Fomento de la Investigación en Estudios de Master program and the predoctoral Contract Formación de Personal Investigador (FPI-UAM). The work has been performed under the Project HPC-EUROPA3 (INFRAIA2016-1-730897), with the support of the EC Research Innovation Action under the H2020 Programme and the CINECA computing center. D.A. and M.G thank funding from the European Union’s Horizon 2020 research and innovation program under the H2020-NMBP-TO-IND-2018-2020/DT-NMBP-09-2018 grant agreement No. 814492 (SIMDOME

Modelizations and Simulations of Nano Devices in nanok calculus

International audienceWe develop a process calculus - the nanok calculus - for modeling, analyzing and predicting the properties of molecular devices. The nanok calculus is equipped with a simple stochastic model, that we use to model and simulate the behavior of a molecular shuttle, a basic nano device currentfly used for building more complex systems

The highly excited-state manifold of guanine: calibration for nonlinear electronic spectroscopy simulations

A computational protocol based on the complete and restricted active space self-consistent field (CASSCF/RASSCF) methods and their second-order perturbation theory extensions (CASPT2/RASPT2) is employed to benchmark the highly excited-state manifold of the DNA/RNA canonical purine nucleobase guanine in vacuo. Several RASPT2 schemes are tested, displaying a steady convergence of electronic transition energies and dipole moments upon active space enlargement toward the reference values. The outcome allows calibrating and optimizing computational efforts by considering cheaper and more approximate RAS schemes that could enable the characterization of the excited-state manifolds of multi-chromophoric systems, such as DNA/RNA nucleobase dimers or multimers. Simulations of two-dimensional electronic spectra show similar trends to those observed on the other purine nucleobase adenine, deviating from this and other pyrimidine nucleobases in featuring its main excited-state absorption signal, embodied by sizable double HOMO to LUMO excitation contributions, in the UV probing window

Risk of congenital anomalies around a municipal solid waste incinerator: a GIS-based case-control study

<p>Abstract</p> <p>Background</p> <p>Waste incineration releases into the environment toxic substances having a teratogenic potential, but little epidemiologic evidence is available on this topic. We aimed at examining the relation between exposure to the emissions from a municipal solid waste incinerator and risk of birth defects in a northern Italy community, using Geographical Information System (GIS) data to estimate exposure and a population-based case-control study design. By modelling the incinerator emissions, we defined in the GIS three areas of increasing exposure according to predicted dioxins concentrations. We mapped the 228 births and induced abortions with diagnosis of congenital anomalies observed during the 1998–2006 period, together with a corresponding series of control births matched for year and hospital of birth/abortion as well as maternal age, using maternal address in the first three months of pregnancy to geocode cases and controls.</p> <p>Results</p> <p>Among women residing in the areas with medium and high exposure, prevalence of anomalies in the offspring was substantially comparable to that observed in the control population, nor dose-response relations for any of the major categories of birth defects emerged. Furthermore, odds ratio for congenital anomalies did not decrease during a prolonged shut-down period of the plant.</p> <p>Conclusion</p> <p>Overall, these findings do not lend support to the hypothesis that the environmental contamination occurring around an incineration plant such as that examined in this study may induce major teratogenic effects.</p

Risk of congenital anomalies around a municipal solid waste incinerator: a GIS-based case-control study.

BACKGROUND: Waste incineration releases into the environment toxic substances having a teratogenic potential, but little epidemiologic evidence is available on this topic. We aimed at examining the relation between exposure to the emissions from a municipal solid waste incinerator and risk of birth defects in a northern Italy community, using Geographical Information System (GIS) data to estimate exposure and a population-based case-control study design. By modelling the incinerator emissions, we defined in the GIS three areas of increasing exposure according to predicted dioxins concentrations. We mapped the 228 births and induced abortions with diagnosis of congenital anomalies observed during the 1998-2006 period, together with a corresponding series of control births matched for year and hospital of birth/abortion as well as maternal age, using maternal address in the first three months of pregnancy to geocode cases and controls. RESULTS: Among women residing in the areas with medium and high exposure, prevalence of anomalies in the offspring was substantially comparable to that observed in the control population, nor dose-response relations for any of the major categories of birth defects emerged. Furthermore, odds ratio for congenital anomalies did not decrease during a prolonged shut-down period of the plant. CONCLUSION: Overall, these findings do not lend support to the hypothesis that the environmental contamination occurring around an incineration plant such as that examined in this study may induce major teratogenic effects

Two-dimensional electronic spectroscopy as a tool for tracking molecular conformations in DNA/RNA aggregates

A computational strategy to simulate two-dimensional electronic spectra (2DES) is introduced, which allows characterising ground state conformations of flexible nucleobase aggregates that play a crucial role in nucleic acid photochemistry

Ultrafast Carotenoid to Retinal Energy Transfer in Xanthorhodopsin Revealed by the Combination of Transient Absorption and Two-Dimensional Electronic Spectroscopy

By comparing two-dimensional electronic spectroscopy (2DES) and Pump-Probe (PP) measurements on xanthorhodopsin (XR) and reduced-xanthorhodopsin (RXR) complexes, the ultrafast carotenoid-to-retinal energy transfer pathway is revealed, at very early times, by an excess of signal amplitude at the associated cross-peak and by the carotenoid bleaching reduction due to its ground state recovery. The combination of the measured 2DES and PP spectroscopic data with theoretical modelling allows a clear identification of the main experimental signals and a comprehensive interpretation of their origin and dynamics. The remarkable velocity of the energy transfer, despite the non-negligible energy separation between the two chromophores, and the analysis of the underlying transport mechanism, highlight the role played by the ground state carotenoid vibrations in assisting the process

Ultra-broadband 2D electronic spectroscopy of carotenoid-bacteriochlorophyll interactions in the LH1 complex of a purple bacterium

International audienc