Hybrid FE/ANN and LPR approach for the inverse identification of material parameters from cutting tests

Accuracy of numerical models based in finite elements (FE), extensively used for simulation of cutting processes, depends strongly on the identification of proper material parameters. Experimental identification of the constitutive law parameters for simulation of cutting processes involves unsolved problems such as the complex testing techniques or the difficulty to reproduce the stress triaxiality state during cutting. This work proposes a methodology for the inverse identification of the material parameters from cutting test. Two hybrid approaches are compared. One of them based on FE and artificial neural networks (ANN). The other one based on FE and local polynomial regression (LPR). Firstly, a FE model is validated with experimental data. Then, ANN and LPR are trained with FE simulations. Finally, the estimated ANN and LPR models are used for the inverse identification of material parameters. This identification is solved as an optimization problem. The FE/LPR approach shows good performance, outperforming the FE/ANN approach.The authors acknowledge the financial support of this work to the Ministry of Science and Education of Spain (under project DPI2008-06746).Publicad

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the Hh morphogen directs tissue patterning according to a concentration gradient. Lipid modifications on Hh are needed to achieve graded distribution, leading to debate about how Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that Hh and its co-receptor Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal Hh secretion and graded signalling. We propose Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen.PostprintPeer reviewe

Long runs of homozygosity are associated with Alzheimer’s disease

Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a finescale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [βAVROH (CI 95%) = 0.070 (0.037–0.104); P = 3.91 × 10−5; βFROH (CI95%) = 0.043 (0.009–0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10−16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10−4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in wholeexome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.Consejería de Salud de la Junta de Andalucía PI-0001/201

Long runs of homozygosity are associated with Alzheimer's disease

Altres ajuts: The Genome Research at Fundació ACE project (GR@ACE) is supported by Fundación bancaria "La Caixa," Grifols SA and Fundació ACE. L.M.R. is supported by Consejería de Salud de la Junta de Andalucía (Grant PI-0001/2017).Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer's disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [ β (CI 95%) = 0.070 (0.037-0.104); P = 3.91 × 10 −5 ; β (CI95%) = 0.043 (0.009-0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10 −16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10 −4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

© 2014 Macmillan Publishers Limited. All rights reserved. The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the Hh morphogen directs tissue patterning according to a concentration gradient. Lipid modifications on Hh are needed to achieve graded distribution, leading to debate about how Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that Hh and its co-receptor Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal Hh secretion and graded signalling. We propose Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen.This work was supported by grants from the Consolidation Program (CSD2007-008-25120) to R.B. and I.G., by grants BFU2011-25987 to I.G., BFU2011-25986 to R.B. and AGL2013-48998-C2-2-R to G.A. from the Spanish MICINN, by Marie Curie FP7 (ITN 238186) and by an institutional grant to the CBMSO from the Fundacion Areces to I.G. and by the Departments of Education and Industry of the Basque Government (PI2009-16 and PI2012/42), and the Bizkaia County to R.B. A.-C.G. and J.R.O.-F.Peer Reviewe

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the Hh morphogen directs tissue patterning according to a concentration gradient. Lipid modifications on Hh are needed to achieve graded distribution, leading to debate about how Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that Hh and its co-receptor Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal Hh secretion and graded signalling. We propose Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen

Imágenes de video submarino como herramienta para la estimación de la abundancia de cigala en nel Golfo de Cádiz

En este artículo se presentan los resultados de la campaña ISUNEPCA_0814 cuyo objetivo principal es la estimación de la abundancia de cigala a partir de imágenes submarinas. El método se basa en el hecho de que esta especie vive en el interior de madrigueras que pueden ser identificadas y cuantificadas en un área conocida, obteniéndose una estimación de la densidad de madrigueras que puede ser usada como un índice de abundancia del stock. Este tipo de campañas son una excelente plataforma para la caracterización y cartografiado de hábitats bentónicos, monitoreo de la biodiversidad marina y evaluación del impacto de la pesca sobre el sustrato. En este sentido, las imágenes submarinas han permitido caracterizar los hábitats presentes, cuantificar la abundancia de otras especies macrobentónicas en el área de distribución de la cigala y su relación con variables ambientales como la temperatura, salinidad, MO, y composición granulométrica.Versión del edito