81 research outputs found

    The Suaineadh Project : a stepping stone towards the deployment of large flexible structures in space

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    The Suaineadh project aims at testing the controlled deployment and stabilization of space web. The deployment system is based on a simple yet ingenious control of the centrifugal force that will pull each of the four daughters sections apart. The four daughters are attached onto the four corners of a square web, and will be released from their initial stowed configuration attached to a central hub. Enclosed in the central hub is a specifically designed spinning reaction wheel that controls the rotational speed with a closed loop control fed by measurements from an onboard inertial measurement sensor. Five other such sensors located within the web and central hub provide information on the surface curvature of the web, and progression of the deployment. Suaineadh is currently at an advanced stage of development: all the components are manufactured with the subsystems integrated and are presently awaiting full integration and testing. This paper will present the current status of the Suaineadh project and the results of the most recent set of tests. In particular, the paper will cover the overall mechanical design of the system, the electrical and sensor assemblies, the communication and power systems and the spinning wheel with its control system

    "Ordinary, the same as anywhere else": notes on the management of spoiled identity in 'marginal' middle class neighbourhoods

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    Urban sociologists are becoming increasingly interested in neighbourhood as a source of middle-class identity. Particular emphasis is currently being given to two types of middle-class neighbourhood; gentrified urban neighbourhoods of ‘distinction’ and inconspicuous ‘suburban landscapes of privilege’. However, there has been a dearth of work on ‘marginal’ middle-class neighbourhoods that are similarly ‘inconspicuous’ rather than distinctive, but less exclusive, thus containing sources of ‘spoiled identity’. This article draws on data gathered from two ‘marginal’ middleclass neighbourhoods that contained a particular source of ‘spoiled identity’: social renters. Urban sociological analyses of neighbour responses to these situations highlight a process of dis-identification with the maligned object, which exacerbates neighbour differences. Our analysis of data from the ‘marginal’ middle-class neighbourhoods suggests something entirely different and Goffmanesque. This entailed the management of spoiled identity, which emphasized similarities rather than differences between neighbours.</p

    Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

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    This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Physiology and pathophysiology of the RANKL/RANK system

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    Juvenile Paget&apos;s disease: The second reported, oldest patient is homozygous for the TNFRSF11B &quot;Balkan&quot; mutation (966_969delTGACinsCTT), which elevates circulating immunoreactive osteoprotegerin levels

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    The oldest person (60 yr) with juvenile Paget&apos;s disease is homozygous for the TNFRSF11B mutation 966_969delTGACinsCTT. Elevated circulating levels of immunoreactive OPG and soluble RANKL accompany this genetic defect that truncates the OPG monomer, preventing formation of OPG homodimers. Introduction: Juvenile Paget&apos;s disease (JPD), a rare autosomal recessive disorder, features skeletal pain, fracture, and deformity from extremely rapid bone turnover. Deafness and sometimes retinopathy also occur. Most patients have diminished osteoprotegerin (OPG) inhibition of osteoclastogenesis caused by homozygous loss-of-function defects in TNFRSF11B, the gene that encodes OPG. Circulating immunoreactive OPG (iOPG) is undetectable with complete deletion of TNFRSF11B but normal with a 3-bp in-frame deletion. Materials and Methods: We summarize the clinical course of a 60-yr-old Greek man who is the second reported, oldest JPD patient, including his response to two decades of bisphosphonate therapy. Mutation analysis involved sequencing all exons and adjacent mRNA splice sites of TNFRSF11B. Over the past 4 yr, we used ELISAs to quantitate his serum iOPG and soluble RANKL (sRANKL) levels. Results: Our patient suffered progressive deafness and became legally blind, although elevated markers of bone turnover have been normal for 6 yr. He carries the same homozygous mutation in TNFRSF11B (966_969delTGACinsCTT) reported in a seemingly unrelated Greek boy and Croatian man who also have relatively mild JPD. This frame-shift deletes 79 carboxyterminal amino acids from the OPG monomer, including a cysteine residue necessary for homodimerization. Nevertheless, serum iOPG and sRANKL levels are persistently elevated. Conclusions: Homozygosity for the TNFRSF11B &quot;Balkan&quot; mutation (966_969delTGACinsCTT) causes JPD in the second reported, oldest patient. Elevated circulating iOPG and sRANKL levels complement evidence that this deletion/insertion omits a cysteine residue at the carboxyterminus needed for OPG homodimerization. © 2007 American Society for Bone and Mineral Research

    Assessing the performance of motorcyclists’ impact protectors in simulated ATD knee and shoulder impacts

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    Objective: Fractures are a common injury among motorcycle riders and can have serious health implications. Impact protection (IP) has been designed to help prevent fractures, yet there are conflicting opinions as to whether this IP does in fact help prevent fractures in real-world crashes. This work aimed to (1) use simulated dummy impacts to examine whether existing types of IP could reduce the force transferred to the underlying bone to below fracture tolerance levels and (2) investigate whether current European Standard (EN 1621-1) test procedures for impact protectors designed for motorcyclists are sufficient to ensure fracture protection. Method: Twenty-three shoulder and 7 knee IP specimens were tested using a 23-kg impactor contacting axially along the clavicle and femur of an anthropomorphic test device (ATD) at an energy level corresponding to the fracture tolerance of these bones. Sixteen IP specimens were the same as those worn by motorcycle riders involved in crashes where injury outcome was known (knee: n = 3; shoulder: n = 13) and the IP had been previously tested to EN 1621-1. Other IP tested represented a wide range of IP available for purchase at a motorcycle accessory store. Double and triple layers of IP were also tested. Energy attenuated during the dummy impacts was compared to energy attenuated when tested to EN 1621-1. Results: Of the 23 shoulder IP tested, the average percentage reduction of transferred force to the shoulder from the baseline test was 7.6 \ub1 4.8%. The percentage reduction of transferred force to the knee from the baseline was 43.9 \ub1 7.5%. The entire group of knee IP tested reduced the transferred force to the knee to below the 10-kN injury threshold for the femur. There was a positive but nonsignificant correlation between the ATD test and the EN 1621-1 impact test performance, suggesting that the European standard test method likely provides a good indication of IP performance. However, given the low correlation coefficient, the relationship between IP performance in the European standard test method and injury protection remains unclear. Conclusion: Though the energy attenuation test method in the European standard may be an appropriate approach, distinct differences in injury protection performance observed between knee and shoulder IP indicate that there may be a need for different performance criteria for IP designated to protect different body regions
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