Effect of sandblasting on low and high-cycle fatigue behaviour after mechanical cutting of a twinning-induced plasticity steel

In the last years, car bodies are increasingly made with new advanced high-strength steels, for both lightweighting and safety purposes. Among these new steels, high-manganese or TWIP steels exhibit a promising combination of strength and toughness, arising from the austenitic structure, strengthened by C, and from the twinning induced plasticity effect. Mechanical cutting such as punching or shearing is widely used for the manufacturing of car body components. This method is known to bring about a very clear plastic deformation and therefore causes a significant increase of mechanical stress and micro-hardness in the zone adjacent to the cut edge. To improve the cut edge quality, surface treatments, such as sandblasting, are often used. This surface treatment generates a compressive residual stress layer in the subsurface region. The monotonic tensile properties and deformation mechanisms of these steels have been extensively studied, as well as the effect of grain size and distribution and chemical composition on fatigue behaviour; however, there is not so much documentation about the fatigue performance of these steels cut using different strategies. Thus, the aim of this work is to analyse the fatigue behaviour of a TWIP steel after mechanical cutting with and without sandblasting in Low and High-Cycle Fatigue regimes. The fatigue behaviour has been determined at room temperature with tensile samples tested with a load ratio of 0.1 and load amplitude control to analyse High-Cycle Fatigue behaviour; and a load ratio of -1 and strain amplitude control to determine the Low-Cycle Fatigue behaviour. Samples were cut by shearing with a clearance value of 5%. Afterwards, a part of the cut specimens were manually blasted using glass microspheres of 40 to 95 microns of diameter as abrasive media. The results show a beneficial effect of the sandblasting process in fatigue behaviour in both regimes, load amplitude control (HCF) and strain amplitude control (LCF) tests, when these magnitudes are low, while no significant differences are observed with higher amplitudes. low-cycle fatigue, high-cycle fatigue, mechanical cutting, sandblasting, high manganese steel, TWIP steel. © The Authors, published by EDP Sciences, 2018.Postprint (published version

Nonviral-Mediated Hepatic Expression of IGF-I Increases Treg Levels and Suppresses Autoimmune Diabetes in Mice

Altres ajuts: This work was supported by grants from Ministerio de Ciencia e Innovación (SAF2005-01262 and SAF2008-00962) and from the European Community (FP6 CLINIGENE, LSHB-CT-2006-018933). X.M.A., J.A., and A.R. were recipients of a predoctoral fellowship from Ministerio de Educación, Cultura y Deporte, and D.C. received a predoctoral fellowship from Instituto de Salud Carlos III, Spain. C.J.M.In type 1 diabetes, loss of tolerance to β-cell antigens results in T-cell-dependent autoimmune destruction of β cells. The abrogation of autoreactive T-cell responses is a prerequisite to achieve long-lasting correction of the disease. The liver has unique immunomodulatory properties and hepatic gene transfer results in tolerance induction and suppression of autoimmune diseases, in part by regulatory T-cell (Treg) activation. Hence, the liver could be manipulated to treat or prevent diabetes onset through expression of key genes. IGF-I may be an immunomodulatory candidate because it prevents autoimmune diabetes when expressed in β cells or subcutaneously injected. Here, we demonstrate that transient, plasmid-derived IGF-I expression in mouse liver suppressed autoimmune diabetes progression. Suppression was associated with decreased islet inflammation and β-cell apoptosis, increased β-cell replication, and normalized β-cell mass. Permanent protection depended on exogenous IGF-I expression in liver nonparenchymal cells and was associated with increased percentage of intrapancreatic Tregs. Importantly, Treg depletion completely abolished IGF-I-mediated protection confirming the therapeutic potential of these cells in autoimmune diabetes. This study demonstrates that a nonviral gene therapy combining the immunological properties of the liver and IGF-I could be beneficial in the treatment of the disease

Insulin-like growth factor 2 overexpression induces β-Cell dysfunction and increases beta-cell susceptibility to damage

The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function

Vascular Endothelial Growth Factor-Mediated Islet Hypervascularization and Inflammation Contribute to Progressive Reduction of β-Cell Mass

Type 2 diabetes (T2D) results from insulin resistance and inadequate insulin secretion. Insulin resistance initially causes compensatory islet hyperplasia that progresses to islet disorganization and altered vascularization, inflammation, and, finally, decreased functional β-cell mass and hyperglycemia. The precise mechanism(s) underlying β-cell failure remain to be elucidated. In this study, we show that in insulin-resistant high-fat diet-fed mice, the enhanced islet vascularization and inflammation was parallel to an increased expression of vascular endothelial growth factor A (VEGF). To elucidate the role of VEGF in these processes, we have genetically engineered β-cells to overexpress VEGF (in transgenic mice or after adeno-associated viral vector-mediated gene transfer). We found that sustained increases in β-cell VEGF levels led to disorganized, hypervascularized, and fibrotic islets, progressive macrophage infiltration, and proinflammatory cytokine production, including tumor necrosis factor-α and interleukin-1β. This resulted in impaired insulin secretion, decreased β-cell mass, and hyperglycemia with age. These results indicate that sustained VEGF upregulation may participate in the initiation of a process leading to β-cell failure and further suggest that compensatory islet hyperplasia and hypervascularization may contribute to progressive inflammation and β-cell mass loss during T2D

New metabolites in the degradation of fluorene by Arthrobacter sp. strain F101

8 pages, 3 figures, 1 table.-- PMID: 9055403 [PubMed].-- PMCID: PMC168377.Identification of new metabolites and demonstration of key enzyme activities support and extend the pathways previously reported for fluorene metabolism by Arthrobacter sp. strain F101. Washed-cell suspensions of strain F101 with fluorene accumulated 9-fluorenone, 4-hydroxy-9-fluorenone, 3-hydroxy-1-indanone, 1-indanone, 2-indanone, 3-(2-hydroxyphenyl) propionate, and a compound tentatively identified as a formyl indanone. Incubations with 2-indanone produced 3-isochromanone. The growth yield with fluorene as a sole source of carbon and energy corresponded to an assimilation of about 34% of fluorene carbon. About 7.4% was transformed into 9-fluorenol, 9-fluorenone, and 4-hydroxy-9-fluorenone. Crude extracts from fluorene-induced cells showed 3,4-dihydrocoumarin hydrolase and catechol 2,3-dioxygenase activities. These results and biodegradation experiments with the identified metabolites indicate that metabolism of fluorene by Arthrobacter sp. strain F101 proceeds through three independent pathways. Two productive routes are initiated by dioxygenation at positions 1,2 and 3,4, respectively. meta cleavage followed by an aldolase reaction and loss of C-1 yield the detected indanones. Subsequent biological Baeyer-Villiger reactions produce the aromatic lactones 3,4-dihydrocoumarin and 3-isochromanone. Enzymatic hydrolysis of the former gives 3-(2-hydroxyphenyl) propionate, which could be a substrate for a beta oxidation cycle, to give salicylate. Further oxidation of the latter via catechol and 2-hydroxymuconic semialdehyde connects with the central metabolism, allowing the utilization of all fluorene carbons. Identification of 4-hydroxy-9-fluorenone is consistent with an alternative pathway initiated by monooxygenation at C-9 to give 9-fluorenol and then 9-fluorenone. Although dioxygenation at 3,4 positions of the ketone apparently occurs, this reaction fails to furnish a subsequent productive oxidation of this compound.This research was funded by a grant from the National Plan for Research (AMB93-0693-C02-02) of the Spanish government. M.C. was in receipt of a doctoral fellowship from the Spanish Ministry of Education.Peer reviewe

Effect of Sandblasting on Low and High-Cycle Fatigue Behaviour after Mechanical Cutting of a Twinning-Induced Plasticity Steel

In the last years, car bodies are increasingly made with new advanced high-strength steels, for both lightweighting and safety purposes. Among these new steels, high-manganese or TWIP steels exhibit a promising combination of strength and toughness, arising from the austenitic structure, strengthened by C, and from the twinning induced plasticity effect. Mechanical cutting such as punching or shearing is widely used for the manufacturing of car body components. This method is known to bring about a very clear plastic deformation and therefore causes a significant increase of mechanical stress and micro-hardness in the zone adjacent to the cut edge. To improve the cut edge quality, surface treatments, such as sandblasting, are often used. This surface treatment generates a compressive residual stress layer in the subsurface region. The monotonic tensile properties and deformation mechanisms of these steels have been extensively studied, as well as the effect of grain size and distribution and chemical composition on fatigue behaviour; however, there is not so much documentation about the fatigue performance of these steels cut using different strategies. Thus, the aim of this work is to analyse the fatigue behaviour of a TWIP steel after mechanical cutting with and without sandblasting in Low and High-Cycle Fatigue regimes. The fatigue behaviour has been determined at room temperature with tensile samples tested with a load ratio of 0.1 and load amplitude control to analyse High-Cycle Fatigue behaviour; and a load ratio of -1 and strain amplitude control to determine the Low-Cycle Fatigue behaviour. Samples were cut by shearing with a clearance value of 5%. Afterwards, a part of the cut specimens were manually blasted using glass microspheres of 40 to 95 microns of diameter as abrasive media. The results show a beneficial effect of the sandblasting process in fatigue behaviour in both regimes, load amplitude control (HCF) and strain amplitude control (LCF) tests, when these magnitudes are low, while no significant differences are observed with higher amplitudes. low-cycle fatigue, high-cycle fatigue, mechanical cutting, sandblasting, high manganese steel, TWIP stee

Economic indicators for automobile claim frequencies

Abstract: This article examines the relationship between observed claim frequencies in the automobile insurance line and the evolution of selected economic magnitudes. From a variety of economic variables, we aim to identify the main factors affecting claim frequencies, while controlling for other legislative and demographic factors. Through a dynamic regression model, the analysis is conducted for three different categories of vehicles and for a variety of coverages. A comprehensive dataset from the main Spanish insurance companies is used to calibrate the model. The evidence might assist companies to improve ratemaking.Resumen: Este artículo examina la relación entre las frecuencias de siniestralidad ob- servadas en la línea de seguros de automóviles y la evolución de magnitudes económicas seleccionadas. A partir de una variedad de variables económicas, nuestro objetivo es identificar los principales factores que afectan a las frecuen- cias de siniestralidad, controlando al mismo tiempo otros factores legislativos y demográficos. A través de un modelo de regresión dinámica, el análisis se realiza para tres categorías diferentes de vehículos y para distintas coberturas. Se utiliza una base de datos de las principales compañías de seguros españolas para calibrar el modelo. La evidencia podría ayudar a las empresas a mejorar su tarificación

Effect of sandblasting on low and high-cycle fatigue behaviour after mechanical cutting of a twinning-induced plasticity steel

In the last years, car bodies are increasingly made with new advanced high-strength steels, for both lightweighting and safety purposes. Among these new steels, high-manganese or TWIP steels exhibit a promising combination of strength and toughness, arising from the austenitic structure, strengthened by C, and from the twinning induced plasticity effect. Mechanical cutting such as punching or shearing is widely used for the manufacturing of car body components. This method is known to bring about a very clear plastic deformation and therefore causes a significant increase of mechanical stress and micro-hardness in the zone adjacent to the cut edge. To improve the cut edge quality, surface treatments, such as sandblasting, are often used. This surface treatment generates a compressive residual stress layer in the subsurface region. The monotonic tensile properties and deformation mechanisms of these steels have been extensively studied, as well as the effect of grain size and distribution and chemical composition on fatigue behaviour; however, there is not so much documentation about the fatigue performance of these steels cut using different strategies. Thus, the aim of this work is to analyse the fatigue behaviour of a TWIP steel after mechanical cutting with and without sandblasting in Low and High-Cycle Fatigue regimes. The fatigue behaviour has been determined at room temperature with tensile samples tested with a load ratio of 0.1 and load amplitude control to analyse High-Cycle Fatigue behaviour; and a load ratio of -1 and strain amplitude control to determine the Low-Cycle Fatigue behaviour. Samples were cut by shearing with a clearance value of 5%. Afterwards, a part of the cut specimens were manually blasted using glass microspheres of 40 to 95 microns of diameter as abrasive media. The results show a beneficial effect of the sandblasting process in fatigue behaviour in both regimes, load amplitude control (HCF) and strain amplitude control (LCF) tests, when these magnitudes are low, while no significant differences are observed with higher amplitudes. low-cycle fatigue, high-cycle fatigue, mechanical cutting, sandblasting, high manganese steel, TWIP steel. © The Authors, published by EDP Sciences, 2018

A genome-wide association study identifies novel players in Na and Fe homeostasis in Arabidopsis thaliana under alkaline-salinity stress

In nature, multiple stress factors occur simultaneously. The screening of natural diversity panels and subsequent Genome-Wide Association Studies (GWAS) is a powerful approach to identify genetic components of various stress responses. Here, the nutritional status variation of a set of 270 natural accessions of Arabidopsis thaliana grown on a natural saline-carbonated soil is evaluated. We report significant natural variation on leaf Na (LNa) and Fe (LFe) concentrations in the studied accessions. Allelic variation in the NINJA and YUC8 genes is associated with LNa diversity, and variation in the ALA3 is associated with LFe diversity. The allelic variation detected in these three genes leads to changes in their mRNA expression and correlates with plant differential growth performance when plants are exposed to alkaline salinity treatment under hydroponic conditions. We propose that YUC8 and NINJA expression patters regulate auxin and jasmonic signaling pathways affecting plant tolerance to alkaline salinity. Finally, we describe an impairment in growth and leaf Fe acquisition associated with differences in root expression of ALA3, encoding a phospholipid translocase active in plasma membrane and the trans Golgi network which directly interacts with proteins essential for the trafficking of PIN auxin transporters, reinforcing the role of phytohormonal processes in regulating ion homeostasis under alkaline salinity