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[EN] In patient specific biomedical simulation, the numerical model is usually created after cumbersome, time consuming procedures which often require highly specialized human work and a great amount of man-hours to be carried out. In order to make numerical simulation available for medical practice, it is of primary importance to reduce the cost associated to these procedures by making them automatic. In this paper a method for the automatic creation of Finite Element (FE) models from medical images is presented. This method is based on the use of a hierarchical structure of nested Cartesian grids in which the medical image is immersed. An efficient h-adaptive procedure conforms the FE model to the image characteristics by refining the mesh on the basis of the distribution of elastic properties associated to the pixel values. As a result, a problem with a reasonable number of degrees of freedom is obtained, skipping the geometry creation stage. All the image information is taken into account during the calculation of the element stiffness matrix, therefore it is straightforward to include the material heterogeneity in the simulation. The proposed method is an adapted version of the Cartesian grid Finite Element Method (cgFEM) for the FE analysis of objects defined by images. cgFEM is an immersed boundary method that uses h-adaptive Cartesian meshes non-conforming to the boundary of the object to be analysed. The proposed methodology, used together with the original geometry-based cgFEM, allows prosthesis geometries to be easily introduced in the model providing a useful tool for evaluating the effect of future implants in a preoperative framework. The potential of this kind of technology is presented by mean of an initial implementation in 2D and 3D for linear elasticity problems. ; With the support of the European Union Framework Programme (FP7) under grant agreement No. 289361 'Integrating Numerical Simulation and Geometric Design Technology (INSIST)', the Ministerio de Economia y Competitividad of Spain ...

[EN] This paper proposes a novel Immersed Boundary Method where the embedded domain is exactly described by using its Computer-Aided Design (CAD) boundary representation with Non-Uniform Rational B-Splines (NURBS) or T-splines. The common feature with other immersed methods is that the current approach substantially reduces the burden of mesh generation. In contrast, the exact boundary representation of the embedded domain allows to overcome the major drawback of existing immersed methods that is the inaccurate representation of the physical domain. A novel approach to perform the numerical integration in the region of the cut elements that is internal to the physical domain is presented and its accuracy and performance evaluated using numerical tests. The applicability, performance, and optimal convergence of the proposed methodology is assessed by using numerical examples in three dimensions. It is also shown that the accuracy of the proposed methodology is independent on the CAD technology used to describe the geometry of the embedded domain. ; With the support of the European Union Framework Program (FP7) under grant No. 289361 INSIST, Ministerio de Economia y Competitividad of Spain (DPI2010-20542)(DPI2013-46317-R), FPI program (BES-2011-044080), and Generalitat Valenciana (PROMETEO/2012/023). R. Sevilla gratefully acknowledges the financial support provided by the Ser Cymru National Research Network in Advanced Engineering and Materials. Y. Zhang was supported in part by the PECASE Award N00014-14-1-0234 and NSF CAREER Award OCI-1149591. ; Marco Alacid, O.; Sevilla, R.; Zhang, Y.; Ródenas, J.; Tur Valiente, M. (2015). Exact 3D boundary representation in finite element analysis based on Cartesian grids independent of the geometry. International Journal for Numerical Methods in Engineering. 103(6):445-468. https://doi.org/10.1002/nme.4914 ; S ; 445 ; 468 ; 103 ; 6 ; Hughes, T. J. R., Cottrell, J. A., & Bazilevs, Y. (2005). Isogeometric analysis: CAD, finite elements, NURBS, exact geometry and mesh ...

1297 1313 121 6 ; S ; "This is the peer reviewed version of the following article: Navarro-Jiménez, José M., Héctor Navarro-García, Manuel Tur, and Juan J. Ródenas. 2019. Superconvergent Patch Recovery with Constraints for Three-dimensional Contact Problems within the Cartesian Grid Finite Element Method. International Journal for Numerical Methods in Engineering 121 (6). Wiley: 1297 1313. doi:10.1002/nme.6266, which has been published in final form at https://doi.org/10.1002/nme.6266. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." [EN] The superconvergent patch recovery technique with constraints (SPR-C) consists in improving the accuracy of the recovered stresses obtained with the original SPR technique by considering known information about the exact solution, like the internal equilibrium equation, the compatibility equation or the Neumann boundary conditions, during the recovery process. In this paper the SPR-C is extended to consider the equilibrium around the contact area when solving contact problems with the Cartesian grid Finite Element Method. In the proposed method, the Finite Element stress fields of both bodies in contact are considered during the recovery process and the equilibrium is enforced by means of the continuity of tractions along the contact surface. The authors would like to thank Generalitat Valenciana (PROMETEO/2016/007), the Spanish Ministerio de Economía, Industria y Competitividad (DPI2017-89816-R), the Spanish Ministerio de Ciencia, Innovación y Universidades (FPU17/03993), and Universitat Politècnica de València (FPI2015) for the financial support to this work. Navarro-Jiménez, J.; Navarro-García, H.; Tur Valiente, M.; Ródenas, JJ. (2020). Superconvergent patch recovery with constraints for three-dimensional contact problems within the Cartesian grid Finite Element Method. International Journal for Numerical Methods in Engineering. 121(6):1297-1313. https://doi.org/10.1002/nme.6266 Wriggers, P. (2006). ...

853 870 62 4 ; S Piegl L, Tiller W (1995) The NURBS Book. Springer, Berlin ; Wriggers P (2008) Nonlinear finite element methods. Springer, Berlin. https://doi.org/10.1007/978-3-540-71001-1 ; [EN] This paper proposes a method of solving 3D large deformation frictional contact problems with the Cartesian Grid Finite Element Method. A stabilized augmented Lagrangian contact formulation is developed using a smooth stress field as stabilizing term, calculated by Zienckiewicz and Zhu Superconvergent Patch Recovery. The parametric definition of the CAD surfaces (usually NURBS) is considered in the definition of the contact kinematics in order to obtain an enhanced measure of the contact gap. The numerical examples show the performance of the method. The authors wish to thank the Spanish Ministerio de Economia y Competitividad the Generalitat Valenciana and the Universitat Politecnica de Valencia for their financial support received through the projects DPI2013-46317-R, Prometeo 2016/007 and the FPI2015 program. Navarro-Jiménez, J.; Tur Valiente, M.; Albelda Vitoria, J.; Ródenas, JJ. (2018). Large deformation frictional contact analysis with immersed boundary method. Computational Mechanics. 62(4):853-870. https://doi.org/10.1007/s00466-017-1533-x ANSYS$$^{\textregistered }$$® Academic Research Mechanical, Release 16.2 Alart P, Curnier A (1991) A mixed formulation for frictional contact problems prone to Newton like solution methods. Comput Methods Appl Mech Eng 92(3):353–375. https://doi.org/10.1016/0045-7825(91)90022-X Annavarapu C, Hautefeuille M, Dolbow JE (2012) Stable imposition of stiff constraints in explicit dynamics for embedded finite element methods. Int J Numer Methods Eng 92(June):206–228. https://doi.org/10.1002/nme.4343 Annavarapu C, Hautefeuille M, Dolbow JE (2014) A Nitsche stabilized finite element method for frictional sliding on embedded interfaces. Part I: single interface. Comput Methods Appl Mech Eng 268:417–436. https://doi.org/10.1016/j.cma.2013.09.002 Annavarapu C, Settgast RR, Johnson SM, Fu ...

"This is an Accepted Manuscript of an article published by Taylor & Francis inVehicle System Dynamics on APR 3 2019, available online: https://www.tandfonline.com/doi/full/10.1080/00423114.2018.1473617." ; [EN] The simulation of the pantograph-catenary dynamic interaction is at present mainly based on deterministic approaches. However, any errors made during the catenary stringing process are sources of variability that can affect the dynamic performance of the system. In this paper, we analyse the influence of dropper length, dropper spacing and support height errors on the current collection quality by applying a classic Monte Carlo method to obtain the probability density functions of several output quantities. The effects of installation errors are also studied for a range of train speeds. Finally, the pre-sag that, on average, produces the best behaviour of the system is identified, allowing for the uncertainty in the catenary installation. The results obtained show the convenience to consider variability in pantograph-catenary dynamic simulations. ; The authors would like to acknowledge the financial support received from the FPU program offered by the Spanish Ministry of Education, Culture and Sports (Ministerio de Educacion, Cultura y Deportes) [grant number FPU13/04191]. The funding provided by the Regional Government of Valencia (Generalitat Valenciana) [PROMETEO/2016/007] and the Spanish Ministry of Economy, Industry and Competitiveness (Ministerio de Economia, Industria y Competitividad) [TRA2017-84736-R] is also acknowledged. ; Gregori Verdú, S.; Tur Valiente, M.; Tarancón Caro, JE.; Fuenmayor Fernández, F. (2019). Stochastic Monte Carlo simulations of the pantograph-catenary dynamic interaction to allow for uncertainties introduced during catenary installation. Vehicle System Dynamics. 57(4):471-492. https://doi.org/10.1080/00423114.2018.1473617 ; S ; 471 ; 492 ; 57 ; 4 ; Bruni, S., Ambrosio, J., Carnicero, A., Cho, Y. H., Finner, L., Ikeda, M., … Zhang, W. (2014). The results of the ...

Neural circuits in the cerebral cortex consist of excitatory pyramidal cells and inhibitory interneurons. These two main classes of cortical neurons follow largely different genetic programs, yet they assemble into highly specialized circuits during development following a very precise choreography. Previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, but the molecular nature of these factors has remained elusive. Here, we identified Neuregulin 3 (Nrg3) as a chemoattractive factor expressed by developing pyramidal cells that guides the allocation of cortical interneurons in the developing cortical plate. Gain- and loss-of-function approaches reveal that Nrg3 modulates the migration of interneurons into the cortical plate in a process that is dependent on the tyrosine kinase receptor ErbB4. Perturbation of Nrg3 signaling in conditional mutants leads to abnormal lamination of cortical interneurons. Nrg3 is therefore a critical mediator in the assembly of cortical inhibitory circuits. ; uterus, and 1 m g/ m L pCAG - Gfp or Nrg3 (kindly provided by C. Lai, Indiana Uni- versity, Bloomington, and subcloned into pCAGGS) plasmids were injected into the lateral ventricle of the telencephalon through the uterine wall. Square electric pulses of 45 V and 50 ms were passed through the uterus five times, spaced 950 ms, using a square pulse electroporator. The uterine horns were placed back in the abdominal cavity, which was then suture closed, and the female was allowed to recover. Explant Cultures For COS cell confrontation assays, COS7 cells were transfected with plasmids encoding Rfp alone, Rfp and Cxcl12 , Rfp and Nrg3 , Rfp and CRD-Nrg1 ,or Rfp and Ig-Nrg1 , and cell aggregates were prepared by diluting transfected cells with Matrigel in a 1:1 proportion. After jellification, COS cell aggregates were cut with a scalpel in small rectangular prisms of approximately 400 3 400 3 800 m m and confronted to MGE explants obtained from GFP-expressing trans- genic mice in 3D Matrigel pads. The cDNA used for expression of Cxcl12 was obtained from Invitrogen (clone number: 3483088; accession number: BC006640). Nrg3 was kindly provided by Cary Lai (Indiana University, Bloo- mington). The sequences used for expression of type I NRG1 ( Ig-Nrg1 ) and type III NRG1 ( CRD-Nrg1 ) correspond to the accession numbers AY648976 and AY648975, respectively. For Cxcl12 chemokine-blocking experiments, SU6656 (Sigma; 330161-87-0) was added to the medium at a final concentra- tion of 15 m M. Previous worked has shown that Src functions downstream of Cxcr4 activation ( Cabioglu et al., 2005 ). In Vitro Focal Electroporation Coronal slice cultures were obtained as described previously ( Anderson et al., 1997 ). A pCAGG-based dsRed plasmid was pressure injected focally into the MGE of coronal slice cultures by a Pneumatic PicoPump through a glass micropipette. Slices were then electroporated within a setup of two hor- izontally oriented platinum electrodes powered by a Electro-Square-Porator, as described before ( Flames et al., 2004 ). Time-Lapse Videomicroscopy Slices were transferred to the stage of an upright Leica DMLFSA or inverted Leica DMIRE2 microscope coupled to a confocal spectral scanning head (Leica; TCS SL) and viewed through 10–60 3 water immersion or 20 3 oil objec- tives. Slices were continuously superfused with warmed (32 C) artificial cere- brospinal fluid at a rate of 1 mL/min or maintained in supplemented Neurobasal medium. To block Cxcl12 function, SU6656 (Sigma; 330161-87-0) was added to the medium at a final concentration of 15 m M. Stripe Assay Purified CXCL12 protein was obtained from PeproTech (250-20A) and used at 1 ng/ m L. GST and EGF-Nrg3-GST were purified using standard protocols and used at 10 m g/mL. Alternating lanes, 50 m m wide, were laid down on a poly- lysine-coated plastic dish. Alexa 555-labeled anti-rabbit IgGs were added to the GST, EGF-Nrg3-GST, and CXCL12 protein solution for lane identification. The lanes were further coated with laminin. MGE explants were dissected out of GFP + brain slices, plated on top of the protein stripes, and incubated in methylcellulose-containing Neurobasal medium for 48 hr. FACS We dissected the sensorimotor cortex of E17.5 embryos and P4 pups following in utero electroporation at E14.5. Cortical tissue was dissociated as described previously ( Catapano et al., 2001 ). GFP + cells were purified using fluorescent activated cell sorting (FACSARIA III; BD Biosciences), and the re- sulting pellet was kept at 80 C. TaqMan Gene Expression Assays We isolated GFP + pyramidal cells by FACS at E17.5 and P4 after in utero elec- troporation at E14.5. mRNA was then extracted using the RNeasy Micro Kit (QIAGEN) according to the manufacturer's instructions. RNA quality was as- sessed using a bioanalyzer (Agilent Technologies) and then retro-transcribed into single-stranded cDNA. The RNA was sent to Unidad Geno ́ mica (Funda- cio ́ n Parque Cientı ́fico de Madrid) for quality control and retro-transcription. Relative gene expression levels from three independent samples were analyzed using custom designed TaqMan low-density array (TLDA) plates (Micro Fluidic Cards; Applied Biosystems). Each plate contained duplicates for all the genes shown in Table S1 . Data were collected and analyzed using the threshold cycle (Ct) relative quantification method. The housekeeping gene 18 RNA was included in the array for assessing RNA quality and sample normalization. Western Blot Cortical lysates were prepared from P30 control and Nestin-Cre;Nrg3 F/F and Nex-Cre;Nrg3 F/F mutants as described before ( Fazzari et al., 2010; Vullhorst et al., 2009 ) and blotted using mouse anti- b -Actin (1:4,000; Sigma) and rabbit anti-Nrg3 (1:500; Abcam). Signals were detected with a luminescent image analyzer (LAS-1000PLUS; Fujifilm) and quantified with Quantity One 1D Anal- ysis Software (Bio-Rad Laboratories). Image Analysis and Quantification Images were acquired using fluorescence microscopes (DM5000B, CTR5000, and DMIRB from Leica, or Apotome.2 from Zeiss) coupled to digital cameras (DC500 or DFC350FX, Leica; OrcaR2, Hamamatsu), or in an inverted Leica TCS SP8 confocal microscope. All images were analyzed with ImageJ (Fiji). For the quantification of migration in MGE explants, the distance migrated by the30furthestcellswasmeasured.Forthequantificationofshort-rangechemo- attraction, the colocalizing area between MGE and COS cells was measured. For the analysis of the interneuron angle of migration, we draw a grid of virtual radial lines (lines perpendicular to the ventricular zone and the pial surface) and oriented each cell in relation to the most adjacent ''radial line.'' Cells that deviated less than 25 from radial lines were considered as radially oriented; those that deviate more than 25 were designated as tangentially oriented. We systematically exclude from this analysis those cells located in the more lateral or medial regions of the cortex, so that the curvature of the slice in those regions would not interfere with our analysis ( Martini et al., 2009 ). For the quan- tification of cell migration in MGE explants, we measured the distance migrated by the30furthest cellsand normalized theaverage migrateddistance tothedis- tancebetweenMGEandCOSexplants.Forthequantificationofthecolocalizing area between migrating interneurons and COS cells in the short-distance confrontation assays, we quantified the colocalizing area using ImageJ (Fiji). Stripes were quantified by counting thenumber of neuronscontained in a virtual grid containing five black and five red lines. The same area was used for all explants. Sections from control and mutant mice were imaged during the same imaging session. Data acquisition was performed using the same laser power, photomultiplier gain, pinhole, and detection filter settings (1,024 3 1,024 resolution; 12 bits). Quantifications were done using ImageJ (Fiji). Layers were drawn following nuclear staining. For in situ hybridization, the area quanti- fied was divided in ten equal bins, and the percentage of cells in each bin was calculated. The bins were then matched to the appropriate layers. Statistical Analyses Statistical analysis was carried out in SPSS (SPSS, Inc.). The p values below 0.05 were considered statistically significant. Data are presented as mean and SEM throughout the manuscript ( Table S3 We thank I. Andrew, S. Bae, M.A. Casillas, M. Ferna ́ndez, and T. Gil for excel-lent technical assistance and laboratory support; A. Caler for excellent support with FACS experiments; G. Expo ́sito for support with imaging; L. Lim for help with quantitative methods; V. Borrell, R. Hevner, C. Lai, V. Pachnis, C. Redies,B. Rico, J.L.R. Rubenstein, and M. Tessier-Lavigne for plasmids and anti-bodies; and A. Barco, M.A. Nieto, and K. Nave for mouse strains. We are grateful to members of the Flames, O.M., and Rico laboratories for stimulating dis- cussions and ideas. This work was supported by grants from European Research Council (ERC-2011-AdG 293683) and the Spanish Government (CSD2007-00023 and SAF2011-28845) to O.M. O.M. is a Wellcome Trust Investigator. ; Sí

[EN] The computational cost required to simulate the pantograph-catenary dynamic interaction can be a limiting factor in certain applications. Specifically, for Hardware-in-the-Loop (HIL) simulations, real-time capabilities of the software are imperative. In this paper, we propose to combine a modal coordinate approach with an offline/online strategy to build a very efficient simulation strategy. The proposed approach preserves the accuracy of the results, compared with those obtained by classical finite element strategies. We also define and validate a criterion for a priori truncation of the modal basis and analyse the effect of explicit treatment of the interaction force. The results show that the method presented could be used in pantograph HIL tests. ; The authors would like to acknowledge the funding provided by the Regional Government of Valencia (PROMETEO/2016/007) and the Spanish Ministry of Economy, Industry and Competitiveness (TRA2017-84736-R). ; Gregori Verdú, S.; Tur Valiente, M.; Pedrosa Sanchez, AM.; Tarancón Caro, JE.; Fuenmayor Fernández, F. (2019). A modal coordinate catenary model for the real-time simulations of the pantograph-catenary dynamic interaction. Finite Elements in Analysis and Design. 162:1-12. https://doi.org/10.1016/j.finel.2019.05.001 ; S ; 1 ; 12 ; 162