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Advances in our understanding of the Universe depend on improvements in sensitivity and angular resolution that can come only with larger telescopes. Telescope diameters increased by almost an order of magnitude in the last century, but that growth has been sporadic, limited mainly by the ability to make bigger mirrors that hold their shape against the dynamic effects of gravity, wind and temperature. Three major advances in mirror technology occurred in the 1980s, including the lightweight honeycomb mirrors made at the Richard F. Caris Mirror Lab at the University of Arizona. In this informal paper, I will describe these technologies and show how they enabled the current generation of 8- to 12-m telescopes and how they are now being used to build telescopes of 25 to 39 m.

Objectives: The aim of this systematic review is to provide an overview of the efficacy of different exercise interventions to counter sarcopenia in older adults. This review will allow the Belgian Society of Gerontology and Geriatrics and other scientific societies to formulate specific exercise recommendations in their Clinical Guidelines for Sarcopenia. Design: We used the method of a systematic umbrella-review. Based on the level of evidence, we formulated specific recommendations for clinical practice. Methods: Two databases (Pubmed and Web Of Science) were searched systematically and methodological quality of the reviews was assessed. Extracted data was than mapped to an exercise category and an overall synthesis (bottom line statements) was formulated for each of these exercise categories. Subsequently, we assigned a rating of the quality of the evidence supporting each bottom line statement. Results: We identified 14 systematic reviews or meta-analyses, encompassing four exercise categories: resistance training, resistance training + nutritional supplementation, multimodal exercise programmes and bloodflow restriction training. Importantly, very few systematic reviews or meta-analyses clearly mentioned baseline sarcopenia status. There is high quality evidence for a positive and significant effect of resistance training on muscle mass, muscle strength, and physical performance. The added effect of nutritional supplementation for resistance training on muscle function appears limited. Blood flow restriction training is a novel training method that has a significant impact on muscle strength. Conclusion: Since sarcopenia is affecting all skeletal muscles in the body, we recommend training the large muscle groups in a total body approach. Although low-intensity resistance training (≤50% 1RM) is sufficient to induce strength gains, we recommend a high-intensity resistance training program (i.e. 80% 1RM) to obtain maximal strength gains. Multimodal exercises and blood flow restriction resistance training may be considered as well.

Type 1 diabetes (T1D) is a multifactorial autoimmune disease with a strong genetic basis. However, evidence suggests a role for environmental factors such as viral infections in triggering disease onset. One viral infection that is highly correlated with T1D is the Coxsackievirus B (CVB) serotype. Sensing of CVB is mediated by the melanoma differentiation-associated protein 5 (MDA5), a cytosolic sensor of dsRNA, which is encoded by the IFIH1 gene. Stimulation of the MDA5 signaling pathway activates the transcription factors IRF3 and NFκB p65, which induce type I IFNs synthesis. Type I IFNs can signal in an autocrine manner through the JAK/STAT pathway to initiate an antiviral transcriptional program. Single nucleotide polymorphisms (SNP) in the IFIH1 gene such as rs1990760, which results in a non-synonymous mutation that changes alanine at position 946 to a threonine, is highly associated with increased risk for T1D. Studies in human PBMCs and mice have demonstrated that the A946T SNP results in an increased sensitivity to viral ligands and subsequently a stronger downstream IFN response. We hypothesize that cells overexpressing the type I diabetes-associated variant 946T will have enhanced downstream signaling and subsequent type I IFN secretion in response to viral ligands and CVB infection. To test this, we stably overexpressed MDA5 with the 946A or 946T variants in HeLa cells. We anticipate that signaling events downstream of CVB infection and synthetic ligand poly (I:C) treatment, such as levels of phosphorylated IRF3 and NFκB p65 will be increased in cells expressing the T1D-associated allele 946T in contrast to cells overexpressing the non-risk allele 946A. Corroborating the increase in IRF3 and NFκB p65 pathway activation, we expect to observe enhanced production and secretion of type I IFNs were measured using HEK Blue IFN reporter cells that may partly explain how CVB infections can trigger autoimmune diabetes. Disclosure J.P. Taylor: None. H.M. Tse: None. Funding National Institutes of Health

While microbial infections can trigger type 1 diabetes (T1D), innate immune activation and the synthesis of free radicals, proinflammatory cytokines, and type 1 interferons contribute to pancreatic β-cell destruction. We previously demonstrated that Coxsackievirus B3 (CB3) infection of Non-Obese Diabetic (NOD) mice can accelerate T1D, partly due to the induction of antiviral signaling pathways including melanoma differentiation-associated protein 5 (MDA5). Single-nucleotide polymorphisms within Ifih1, the gene encoding for MDA5, is associated with multiple autoimmune diseases including T1D, but the molecular mechanism contributing to innate immune dysregulation is not known. Since T1D is a chronic proinflammatory autoimmune disease involving MDA5, we hypothesized that attenuated MDA5 expression and signaling can delay diabetogenic viral-accelerated T1D. We generated NOD mice mutated in Ifih1 that exhibited a delay in spontaneous T1D due to the loss of MDA5 expression (NOD.Ifih1-m1) or an in-frame deletion in the helicase domain that decreased MDA5 synthesis (NOD.Ifih1-m4). Interestingly, CB3-infected NOD and NOD.Ifih1-m1 mice displayed virus-accelerated T1D, but NOD.Ifih1-m4 (n=9 per group) mice were significantly (p < 0.001) delayed. CB3-infected NOD.Ifih1-m4 mice exhibited a 5-fold decrease in IFN-β synthesis in the pancreas, the reduction in inflammation may be a driving factor to prevent the induction of autoimmunity. The Ifih1-m4 mutation did not compromise pancreatic viral clearance, and this was complemented by a ∼34% and ∼32% reduction in pancreas-infiltrating CD8 T cells and activated macrophages (F4/80+, I-Ag7+), respectively, in comparison to CB3-infected NOD mice. The protective Ifih1-m4 mutation may establish an acute level of type 1 interferons and islet-infiltrating lymphocytes to sufficiently inhibit CB3 replication without mediating bystander activation of autoreactive T cells, preventing virus-accelerated autoimmune diabetes. Disclosure S.I. Blum: None. Y. Chen: None. H.M. Tse: None. Funding American Diabetes Association (7-12-CD-11 to H.M.T.)

Islet transplantation can restore glucose homeostasis in patients with type 1 diabetes (T1D), however, limited islet availability, toxicity of immunosuppressants, and poor graft survival impede clinical application. We hypothesize that islet encapsulation with coatings consisting of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), will provide immunoprotection and maintain β-cell function after transplantation. (PVPON/TA)-encapsulated syngeneic islets (n=13) significantly delayed graft failure without immunosuppression after transplantation under the kidney capsule into diabetic non-obese diabetic (NOD) mice by more than 30 days compared to non-encapsulated grafts (n= 13; p=0.0021). Histology of islet engrafted kidneys demonstrated increased insulin, glucagon, and somatostatin positivity within encapsulated grafts compared to non-encapsulated grafts and was corroborated with enhanced glucose responsiveness following an intraperitoneal glucose tolerance test (n=9, p=0.0032). To define the immunoprotective properties of (PVPON/TA) coatings, flow cytometric analysis of islet grafts at day 7 post-transplantation displayed fewer MHC-II expressing cells compared to non-encapsulated controls. Gene expression of islet grafts at 5 days post-transplant displayed a significant increase in Ins2 (p Disclosure J. Barra: None. V. Kozlovskaya: None. E. Kharlampieva: None. G. Korbutt: None. H.M. Tse: None. Funding American Diabetes Association (7-12-CD-11 to H.M.T.); JDRF (1-SRA-2015-42-A-N)

In this paper, the experimental protocol which we disclose is designed to identify the values for both the constant in the Kozeny/Carman model, which relates to the linear component of permeability, and the variable kinetic coefficient in the newly minted Q- modified Ergun model, which relates to the non-linear components of permeability, without involving any new theoretical development. Moreover, kinetic contributions to measured pressure gradient, which are not accounted for in some currently accepted empirical fluid flow equations, such as Poiseuille’s for flow in empty conduits and Kozeny/Carman for flow in packed conduits, but which nevertheless contribute to measured pressure drop and thus hamper the identification of the value of the constant relative to the laminar component, are captured and lumped together into a single variable kinetic parameter-the kinetic coefficient.

[Departement_IRSTEA]Ecotechnologies [ADD1_IRSTEA]Équiper l'agriculture; National audience

International audience; The possibility to shape glass easily and in all kind of forms for applications in our everyday life is one of the key factors to its success. The fabrication of a glass article comprises a succession of steps, often starting from a hot glass melt that is shaped during its cooling. The product can then be worked at lower temperatures, to modify its dimensions or its surface finish. In this chapter, the shaping processes at both high and low temperatures are presented. In a first part, the different forming processes (shaping at high temperature) developed by the glass industry are illustrated, and a specific emphasis is given to glass viscosity, a key parameter in these processes. In the second part of the chapter, the shaping processes occurring at low temperatures, such as cutting or grinding, are described. In this section, specific attention is given to the mechanical behavior of the glass during the process as well as to machining parameters. © 2019, Springer Nature Switzerland AG.

Coxsackievirus B3 (CVB3) infection has been associated with triggering Type 1 diabetes (T1D), potentially due to direct β-cell damage and bystander activation of autoreactive T cells. CVB3-infection of Non-Obese Diabetic (NOD) mice accelerates T1D onset, in part due to melanoma differentiation-associated protein 5 (MDA5)-dependent antiviral responses. However, the role of MDA5 on immune cells during T1D remains unclear. By using mice that contain an in-frame deletion within the helicase 1 domain of MDA5 (ΔHel1) or lack MDA5 expression (KO), we can test the hypothesis that reduced MDA5 expression impairs IFN-α/β synthesis, immune cell activation, and T1D onset. NOD and KO mice develop T1D equally, but ΔHel1 mice exhibit delayed spontaneous and CVB3-accelerated T1D. During spontaneous T1D, 12-week-old ΔHel1 mice had a significant reduction in TNF+ F4/80+ macrophages (MΦ) (1.6-fold), perforin+ CD8+ T cells (13.1-fold), and IFNγ+ CD4+ T cells (6.1-fold), compared to NOD and KO mice. ΔHel1 mice had a significant reduction in pancreatic IFN-α (2.2-fold) and IFN-β (3.1-fold) levels compared to NOD mice following CVB3-infection. CVB3-infected ΔHel1 mice had a significant decrease in pancreatic TNF+ F4/80+ MΦ (2-fold) compared to NOD and KO mice. However, ΔHel1 and KO mice had reduced pancreatic perforin+ CD8+ T cells (2.5-fold) and IFNγ+ CD4+ T cells (1.8-fold) compared to NOD mice following CVB3 infection. The ΔHel1 mutation decreased basal and CVB3-responsive MΦ and T cells within the pancreata thereby delaying T1D onset. Yet, loss of MDA5 expression failed to delay T1D indicating MDA5-dependant responses may be required to prevent T1D. Future studies will determine if T1D onset is dictated by MDA5 dsRNA binding and/or ATPase activity.

Background: Alveolar macrophages (AMs) are resident inflammatory cells in the lung that serve as early sentinels of infection or injury. We have identified thioredoxin reductase 1 inhibition by gold compounds increases activation of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent pathways to attenuate inflammatory responses. The present studies utilized murine alveolar macrophages (MH-S) to test the hypothesis that the gold compound, auranofin (AFN), decreases interleukin (IL)-1β expression through NRF2-mediated interactions with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway genes and/or increases in glutathione synthesis. Methods: MH-S cells were treated with AFN and lipopolysaccharide (LPS) and analyzed at 6 and 24 h. The Il1b promoter was analyzed by chromatin immunoprecipitation for direct interaction with NRF2. Results: Expression of IL-1β, p-IκBα, p-p65 NF-kB, and NOD-, LRR-, and pyrin domain-containing protein 3 were elevated by LPS exposure, but only IL-1β expression was suppressed by AFN treatment. Both AFN and LPS treatments increased cellular glutathione levels, but attenuation of glutathione synthesis by buthionine sulfoximine (BSO) did not alter expression of Il-1β. Analysis revealed direct NRF2 binding to the Il1b promoter which was enhanced by AFN and inhibited the transcriptional activity of DNA polymerase II. Conclusions: Our data demonstrate that AFN-induced NRF2 activation directly suppresses IL-1β synthesis independent of NFκB and glutathione-mediated antioxidant mechanisms. NRF2 binding to the promoter region of IL1β directly inhibits transcription of the IL1β gene. Collectively, our research suggests that gold compounds elicit NRF2-dependent pulmonary protection by suppressing macrophage-mediated inflammation.