optimisation of industrial parts by mesh morphing enabled automatic shape sculpting

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Barrier-to-autointegration factor (BAF) involvement in prelamin a-related chromatin organization changes

Chromatin disorganization is one of the major alterations linked to prelamin A processing impairment. In this study we demonstrate that BAF is necessary to modulate prelamin A effects on chromatin structure. We show that when prelamin A and BAF cannot properly interact no prelamin A-dependent effects on chromatin occur; similar to what is observed in human Nestor Guillermo Progeria Syndrome cells harboring a BAF mutation, in HEK293 cells expressing a BAF mutant unable to bind prelamin A, or in siRNA mediated BAF-depleted HEK293 cells expressing prelamin A. BAF is necessary to induce histone trimethyl-H3K9 as well as HP1-alpha and LAP2-alpha nuclear relocalization in response to prelamin A accumulation. These findings are enforced by electron microscopy evaluations showing how the prelamin A-BAF interaction governs overall chromatin organization. Finally, we demonstrate that the LAP2-alpha nuclear localization defect observed in HGPS cells involves the progerin-BAF interaction, thus establishing a functional link between BAF and prelamin A pathological forms

Crack Propagation Analysis of Near-Surface Defects with Radial Basis Functions Mesh Morphing

Abstract Fracture mechanics analysis is nowadays adopted in several industrial fields to assess the capability of components to withstand fatigue loads. Finite Element Method (FEM) is a well-established tool for the evaluation of flaw Stress Intensity Factors (SIF) and for the survey of its propagation. Nevertheless the study of the growth of near-surface circular and elliptical cracks is still an arduous task to be faced with FEM. In fact, the interaction of the flaw with free surfaces leads the crack front to assume complex shapes, whose simulation cannot be easily accomplished. A possible answer to deal with such a problem is to use the mesh morphing technique, a nodal relocation methodology, that allows to cover different problems. In fact, with mesh morphing, it is possible to fit the baseline flaw front with the desired shape (generic shape) and to automatically simulate its evolution at a certain number of cycles. In the proposed work this approach is demonstrated exploiting ANSYS Mechanical as FEM tool and RBF Morph ACT Extension as mesh-morpher. The results of the proposed workflow are compared with those available in literature

Spatial and Temporal evolution of the subsidence phenomena in the Italian Peninsula

A large number of continuous GNSS (CGNSS) stations are nowadays available in Italy, this has already allowed an accurate monitoring of the horizontal and vertical kinematic pattern in the Italian peninsula in terms of linear trends. The crustal displacements can be considered as the result of several contributions: global, regional and local tectonic processes, climatic and meteorological phenomena, but also human activities. In particular, the groundwater exploitation for agricultural and industrial purposes and the extractive activities of gas, oil and geothermal fluids can induce displacements that can be greater than the ones due to natural contributions. Human activities could induce rapid changes in the local dynamic of the Earth crust and usually have stronger impact on the vertical component. Therefore, an accurate monitoring of the vertical displacements that takes into account also the spatial heterogeneity of the human activities is a major issue. In order to monitor and study the vertical velocity field in the Italian area, the observation of more than 600 CGNSS sites have been analysed using the GAMIT software package. The interdistances between the considered sites is about 40-50 Km and should allow a fairly good definition of the vertical velocity field and to study the possible spatial evolution of the pattern. The relatively long time interval of data acquisition (2001-2018) provides an important data set that make possible to identify different time evolutions with respect to the linear trend usually adopted in the GNSS time series analysis. The present vertical velocity field in the Italian peninsula and in particular along the coastal areas and neighbour zones will be shown. Preliminary studies about the spatial and temporal evolution of the subsidence phenomena in these areas will be also discussed

Spatial and Temporal evolution of the subsidence phenomena in the Italian Peninsula

A large number of continuous GNSS (CGNSS) stations are nowadays available in Italy, this has already allowed an accurate monitoring of the horizontal and vertical kinematic pattern in the Italian peninsula in terms of linear trends. The crustal displacements can be considered as the result of several contributions: global, regional and local tectonic processes, climatic and meteorological phenomena, but also human activities. In particular, the groundwater exploitation for agricultural and industrial purposes and the extractive activities of gas, oil and geothermal fluids can induce displacements that can be greater than the ones due to natural contributions. Human activities could induce rapid changes in the local dynamic of the Earth crust and usually have stronger impact on the vertical component. Therefore, an accurate monitoring of the vertical displacements that takes into account also the spatial heterogeneity of the human activities is a major issue. In order to monitor and study the vertical velocity field in the Italian area, the observation of more than 600 CGNSS sites have been analysed using the GAMIT software package. The interdistances between the considered sites is about 40-50 Km and should allow a fairly good definition of the vertical velocity field and to study the possible spatial evolution of the pattern. The relatively long time interval of data acquisition (2001-2018) provides an important data set that make possible to identify different time evolutions with respect to the linear trend usually adopted in the GNSS time series analysis. The present vertical velocity field in the Italian peninsula and in particular along the coastal areas and neighbour zones will be shown. Preliminary studies about the spatial and temporal evolution of the subsidence phenomena in these areas will be also discussed

Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: altered intermolecular interaction with emerin and implications for gene transcription

Familial partial lipodystrophy is an autosomal dominant disease caused by mutations of the LMNA gene encoding alternatively spliced lamins A and C. Abnormal distribution of body fat and insulin resistance characterize the clinical phenotype. In this study, we analyzed primary fibroblast cultures from a patient carrying an R482L lamin A/C mutation by a morphological and biochemical approach. Abnormalities were observed consisting of nuclear lamin A/C aggregates mostly localized close to the nuclear lamina. These aggregates were not bound to either DNA-containing structures or RNA splicing intranuclear compartments. In addition, emerin did not colocalize with nuclear lamin A/C aggregates. Interestingly, emerin failed to interact with lamin A in R482L mutated fibroblasts in vivo, while the interaction with lamin C was preserved in vitro, as determined by coimmunoprecipitation experiments. The presence of lamin A/C nuclear aggregates was restricted to actively transcribing cells, and it was increased in insulin-treated fibroblasts. In fibroblasts carrying lamin A/C nuclear aggregates, a reduced incorporation of bromouridine was observed, demonstrating that mutated lamin A/C in FPLD cells interferes with RNA transcription

Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning

Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1. Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy, formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage, adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.We thank FPLD2 patients for donating biological samples. We thank the Italian Network for Laminopathies and the European Consortium of Lipodystrophies (ECLip) for support and helpful discussion. We thank Aurelio Valmori for the technical support. The studies were supported by Rizzoli Orthopedic Institute “5 per mille” 2014 project to MC, AIProSaB project 2016 and Fondazione Del Monte di Bologna e Ravenna grant 2015–2016 “New pharmacological approaches in bone laminopathies based on the use of antibodies neutralizing TGF beta 2” to GL. GL is also supported by PRIN MIUR project 2015FBNB5Y.S

miRNAs Expression Analysis in Paired Fresh/Frozen and Dissected Formalin Fixed and Paraffin Embedded Glioblastoma Using Real-Time PCR

miRNAs are small molecules involved in gene regulation. Each tissue shows a characteristic miRNAs epression profile that could be altered during neoplastic transformation. Glioblastoma is the most aggressive brain tumour of the adult with a high rate of mortality. Recognizing a specific pattern of miRNAs for GBM could provide further boost for target therapy. The availability of fresh tissue for brain specimens is often limited and for this reason the possibility of starting from formalin fixed and paraffin embedded tissue (FFPE) could very helpful even in miRNAs expression analysis. We analysed a panel of 19 miRNAs in 30 paired samples starting both from FFPE and Fresh/Frozen material. Our data revealed that there is a good correlation in results obtained from FFPE in comparison with those obtained analysing miRNAs extracted from Fresh/Frozen specimen. In the few cases with a not good correlation value we noticed that the discrepancy could be due to dissection performed in FFPE samples. To the best of our knowledge this is the first paper demonstrating that the results obtained in miRNAs analysis using Real-Time PCR starting from FFPE specimens of glioblastoma are comparable with those obtained in Fresh/Frozen samples

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