612 research outputs found

    Mediatization of the Early Automobile: A Visual Analysis of the Illustrated Press in the late 19th and Early 20th century

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    The paper presents a digital analysis of automobile imagery in the early 20th-century press, examining the mediatization of the anti-car movement and the role images played in conveying and furthering the activist discourse. To investigate the phenomenon, the author compiled and analyzed over 5,000 images from in 185 journals published in 45 cities between 1891 and 1950. The analysis revealed a preponderance of positive representations of the automobile in the press, whilst evidence of negative sentiment towards the automobile, such as protests and accidents, was conspicuously absent, with the exception of satirical publications

    Implementing the European Space Agency’s SentiNel application platform’s open-source Python module for differential synthetic aperture radar interferometry coseismic ground deformation from Sentinel-1 data

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    Differential SAR Interferometry is a largely exploited technique to study ground deformations. A key application is the detection of the effects promoted by earthquakes, including detailed variations in ground deformations at different scales. In this work, an implemented Python script (Snap2DQuake) based on the “snappy” module by SNAP software 9.0.8 (ESA) for the processing of satellite imagery is proposed. Snap2DQuake is aimed at producing detailed coseismic deformation maps using Sentinel-1 C-band data by the DInSAR technique. With this alternative approach, the processing is simplified, and several issues that may occur using the software are solved. The proposed tool has been tested on two case studies: the Mw 6.4 Petrinja earthquake (Croatia, December 2020) and the Mw 5.7 to Mw 6.3 earthquakes, which occurred near Tyrnavós (Greece, March 2021). The earthquakes, which occurred in two different tectonic contexts, are used to test and verify the validity of Snap2DQuake. Snap2DQuake allows us to provide detailed deformation maps along the vertical and E-W directions in perfect agreement with observations reported in previous works. These maps offer new insights into the deformation pattern linked to earthquakes, demonstrating the reliability of Snap2DQuake as an alternative tool for users working on different applications, even with basic coding skills.Peer ReviewedPostprint (published version

    Une Europe par les arts ? Les périodiques illustrés au-delà du Musée imaginaire

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    Existe-t- il un musée imaginaire européen ? Cet article aborde la question par le biais des illustrations de presse des années 1880-1960. Dans les périodiques illustrés de cette époque, les images d’art traversèrent mieux les frontières que les images non artistiques, en particulier en Europe. Mais plutôt que de conclure à un musée imaginaire européen, une étude multiscalaire plus fine incite à se pencher sur les facteurs sociaux, esthétiques, économiques et techniques de la circulation imprimée des images artistiques

    Emerging perspectives on laminopathies

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    Giovanna Lattanzi,1,2 Sara Benedetti,3 Maria Rosaria D'Apice,4 Lorenzo Maggi,5 Nicola Carboni,6 Emanuela Scarano,7 Luisa Politano8 1National Research Council of Italy, Institute for Molecular Genetics (CNR-IGM), Unit of Bologna, 2Rizzoli Orthopedic Institute, Laboratory of Musculoskeletal Cell Biology, Bologna, 3Laboratory of Clinical Molecular Biology and Cytogenetics, San Raffaele Scientific Institute, Milan, 4Fondazione Policlinico Tor Vergata, Rome, 5Neuromuscular Diseases and Neuroimmunology Unit, IRCCS Neurological Institute C Besta, Milan, 6Division of Neurology, Hospital San Francesco, Nuoro, 7Pediatric Endocrinology and Rare Diseases Unit, Department of Pediatrics, S Orsola-Malpighi University Hospital, University of Bologna, Bologna, 8Department of Experimental Medicine, Cardiomyology and Medical Genetics, Second University of Naples, Naples, Italy Abstract: Laminopathies are a group of inherited disorders caused by mutations in the lamin A/C gene, and can affect diverse organs or tissues, or can be systemic, causing premature aging. In the present review, we report on the composition and structure of the nuclear lamina and the role of lamins in nuclear mechanics and their involvement in human diseases, and provide some examples of laminopathies and current therapeutic approaches. Keywords: lamin A/C, emerin, laminopathies, Emery–Dreifuss muscular dystrophy, Hutchinson–Gilford progeri

    Innocent strategies as presheaves and interactive equivalences for CCS

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    Seeking a general framework for reasoning about and comparing programming languages, we derive a new view of Milner's CCS. We construct a category E of plays, and a subcategory V of views. We argue that presheaves on V adequately represent innocent strategies, in the sense of game semantics. We then equip innocent strategies with a simple notion of interaction. This results in an interpretation of CCS. Based on this, we propose a notion of interactive equivalence for innocent strategies, which is close in spirit to Beffara's interpretation of testing equivalences in concurrency theory. In this framework we prove that the analogues of fair and must testing equivalences coincide, while they differ in the standard setting.Comment: In Proceedings ICE 2011, arXiv:1108.014

    Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma

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    Abstract Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and >IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HRA). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti–IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HRA, and IGFIR) act complementarily for an IGF-II–mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth. [Cancer Res 2009;69(6):2443–52

    Vitamin D responsive elements within the HLA-DRB1 promoter region in Sardinian multiple sclerosis associated alleles

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    Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects). Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients

    Elevated TGF \u3b22 serum levels in Emery-Dreifuss Muscular Dystrophy: Implications for myocyte and tenocyte differentiation and fibrogenic processes

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    Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF \u3b22) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF \u3b22 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss Muscular Dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF \u3b22-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF \u3b22 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF \u3b22-dependent mechanisms were also determined in laminopathic cells, where TGF \u3b22 activated AKT/mTOR phosphorylation. These data show that TGF \u3b22 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF \u3b22 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies

    Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey

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    Objective: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. The aim of this study was to assess the prevalence of SMA and treatment prescription in Italy. Methods: An online survey was distributed to 36 centers identified by the Italian government as referral centers for SMA. Data on the number of patients with SMA subdivided according to age, type, SMN2 copy number, and treatment were collected. Results: One thousand two hundred fifty-five patients with SMA are currently followed in the Italian centers with an estimated prevalence of 2.12/100,000. Of the 1,255, 284 were type I, 470 type II, 467 type III, and 15 type IV with estimated prevalence of 0.48, 0.79, 0.79 and 0.02/100,000, respectively. Three patients with SMA 0 and 16 presymptomatic patients were also included. Approximately 85% were receiving one of the available treatments. The percentage of treated patients decreased with decreasing severity (SMA I: 95.77%, SMA II: 85.11%, SMA III: 79.01%). Discussion: The results provide for the first time an estimate of the prevalence of SMA at the national level and the current distribution of patients treated with the available therapeutical options. These data provide a baseline to assess future changes in relation to the evolving therapeutical scenario
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