The Year 3000

First published in 1897, The Year 3000 is the most daring and original work of fiction by the prominent Italian anthropologist Paolo Mantegazza. A futuristic utopian novel, the book follows two young lovers who, as they travel from Rome to the capital of the United Planetary States to celebrate their “mating union,” encounter the marvels of cultural and scientific advances along the way. Intriguing in itself, The Year 3000 is also remarkable for both its vision of the future (predicting an astonishing array of phenomena from airplanes, artificial intelligence, CAT scans, and credit cards to controversies surrounding divorce, abortion, and euthanasia) and the window it opens on fin de siècle Europe. Published here for the first time in English, this richly annotated edition features an invaluable introductory essay that interprets the intertextual and intercultural connections within and beyond Mantegazza’s work. For its critical contribution to early science fiction and for its insights into the hopes, fears, and clash of values in the Western world of both Mantegazza’s time and our own, this book belongs among the visionary giants of speculative literature

Periodic controllers for vibration reduction using actively twisted blades

This paper compares two periodic control methods, the optimal H2 and the periodic static output feedback (POF), to reduce the helicopter rotor vibrations. Actively twisted blades with Macro-Fibre Composite (MFC) piezoelectric actuators are used. The design model is based on a simplified aerodynamic model and on a multi-body model of the Bo 105 isolated rotor with the original blades replaced by actively twisted ones. The performance of the two controllers in alleviating hub loads is verified with improved simulations based on a free-wake model

Idiopathic Inflammatory Myopathies: A Review of Immunopathological Features and Current Models of Pathogenesis

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Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

AbstractExcessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition

A New Thiopurine S-Methyltransferase Haplotype Associated With Intolerance to Azathioprine

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The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors.

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an intense trafficking of the leukemic cells between the peripheral blood and lymphoid tissues. It is known that the ability of lymphocytes to recirculate strongly depends on their capability to rapidly rearrange their cytoskeleton and adapt to external cues; however, little is known about the differences occurring between CLL and healthy B cells during these processes. To investigate this point, we applied a single-cell optical (super resolution microscopy) and nanomechanical approaches (atomic force microscopy, real-time deformability cytometry) to both CLL and healthy B lymphocytes and compared their behavior. We demonstrated that CLL cells have a specific actomyosin complex organization and altered mechanical properties in comparison to their healthy counterpart. To evaluate the clinical relevance of our findings, we treated the cells in vitro with the Bruton's tyrosine kinase inhibitors and we found for the first time that the drug restores the CLL cells mechanical properties to a healthy phenotype and activates the actomyosin complex. We further validated these results in vivo on CLL cells isolated from patients undergoing ibrutinib treatment. Our results suggest that CLL cells' mechanical properties are linked to their actin cytoskeleton organization and might be involved in novel mechanisms of drug resistance, thus becoming a new potential therapeutic target aiming at the normalization of the mechanical fingerprints of the leukemic cells.CS project is supported by Associazione Italiana per la Ricerca sul Cancro AIRC under IG 2018 - ID 21332 project. OO gratefully acknowledges financial support from the German Federal Ministry of Education and Research (ZIK grant to OO under grant agreement no. 03Z22CN11) as well as from the German Center for Cardiovascular Research (Postdoc start-up grant to OO under grant agreement no. 81X3400107). CAM acknowledges financial support from the Italian Ministry of University and Research (MIUR) Department of Excellence project PREMIA (PREcision MedIcine Approach: bringing biomarker research to clinics). STED microscopy was conducted at the Microscopy & Dynamic Imaging Unit, CNIC, ICTS-ReDib, co-funded by MCIN/AEI/10.13039/501100011033, and FEDER “Una manera de hacer Europa” (#ICTS-2018-04-CNIC-16). The CNIC is supported by the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). Schemes in figures 1, 2, 3 and 4 have been generated with BioRender.com. Funding for the project was provided by the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no 282510 – BLUEPRINT.S

E-ELT M4 adaptive unit final design and construction: a progress report

The E-ELT M4 adaptive unit is a fundamental part of the E-ELT: it provides the facility level adaptive optics correction that compensates the wavefront distortion induced by atmospheric turbulence and partially corrects the structural deformations caused by wind. The unit is based on the contactless, voice-coil technology already successfully deployed on several large adaptive mirrors, like the LBT, Magellan and VLT adaptive secondary mirrors. It features a 2.4m diameter flat mirror, controlled by 5316 actuators and divided in six segments. The reference structure is monolithic and the cophasing between the segments is guaranteed by the contactless embedded metrology. The mirror correction commands are usually transferred as modal amplitudes, that are checked by the M4 controller through a smart real-time algorithm that is capable to handle saturation effects. A large hexapod provides the fine positioning of the unit, while a rotational mechanism allows switching between the two Nasmyth foci. The unit has entered the final design and construction phase in July 2015, after an advanced preliminary design. The final design review is planned for fall 2017; thereafter, the unit will enter the construction and test phase. Acceptance in Europe after full optical calibration is planned for 2022, while the delivery to Cerro Armazones will occur in 2023. Even if the fundamental concept has remained unchanged with respect to the other contactless large deformable mirrors, the specific requirements of the E-ELT unit posed new design challenges that required very peculiar solutions. Therefore, a significant part of the design phase has been focused on the validation of the new aspects, based on analysis, numerical simulations and experimental tests. Several experimental tests have been executed on the Demonstration Prototype, which is the 222 actuators prototype developed in the frame of the advanced preliminary design. We present the main project phases, the current design status and the most relevant results achieved by the validation tests

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo