171 research outputs found

    Effects of expected-value information and display format on recognition of aircraft subsystem abnormalities

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    This study identifies improved methods to present system parameter information for detecting abnormal conditions and to identify system status. Two workstation experiments were conducted. The first experiment determined if including expected-value-range information in traditional parameter display formats affected subject performance. The second experiment determined if using a nontraditional parameter display format, which presented relative deviation from expected value, was better than traditional formats with expected-value ranges included. The inclusion of expected-value-range information onto traditional parameter formats was found to have essentially no effect. However, subjective results indicated support for including this information. The nontraditional column deviation parameter display format resulted in significantly fewer errors compared with traditional formats with expected-value-ranges included. In addition, error rates for the column deviation parameter display format remained stable as the scenario complexity increased, whereas error rates for the traditional parameter display formats with expected-value ranges increased. Subjective results also indicated that the subjects preferred this new format and thought that their performance was better with it. The column deviation parameter display format is recommended for display applications that require rapid recognition of out-of-tolerance conditions, especially for a large number of parameters

    Recent origin of low trabecular bone density in modern humans

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    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations

    Nintedanib decreases muscle fibrosis and improves muscle function in a murine model of dystrophinopathy

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    Duchenne muscle dystrophy (DMD) is a genetic disorder characterized by progressive skeletal muscle weakness. Dystrophin deficiency induces instability of the sarcolemma during muscle contraction that leads to muscle necrosis and replacement of muscle by fibro-adipose tissue. Several therapies have been developed to counteract the fibrotic process. We report the effects of nintedanib, a tyrosine kinase inhibitor, in the mdx murine model of DMD. Nintedanib reduced proliferation and migration of human fibroblasts in vitro and decreased the expression of fibrotic genes such as COL1A1, COL3A1, FN1, TGFB1, and PDGFA. We treated seven mdx mice with 60 mg/kg/day nintedanib for 1 month. Electrophysiological studies showed an increase in the amplitude of the motor action potentials and an improvement of the morphology of motor unit potentials in the animals treated. Histological studies demonstrated a significant reduction of the fibrotic areas present in the skeletal muscles. Analysis of mRNA expression from muscles of treated mice showed a reduction in Col1a1, Col3a1, Tgfb1, and Pdgfa. Western blot showed a reduction in the expression of collagen I in skeletal muscles. In conclusion, nintedanib reduced the fibrotic process in a murine model of dystrophinopathy after 1 month of treatment, suggesting its potential use as a therapeutic drug in DMD patients.España, Ministerio de EconomĂ­a y Competitividad BFU2016-74975-PEspaña, Instituto RamĂłn y Cajal PI13/0134

    Lfc subcellular localization and activity is controlled by αv-class integrin

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    Fibronectin (FN)-binding integrins control a variety of cellular responses through Rho GTPases. The FN-binding integrins, αvÎČ3 and α5ÎČ1, are known to induce different effects on cell morphology and motility. Here, we report that FN-bound αvÎČ3 integrin, but not FN-bound α5ÎČ1 integrin, triggers the dissociation of the RhoA GEF Lfc (also known as GEF-H1 and ARHGEF2 in humans) from microtubules (MTs), leading to the activation of RhoA, formation of stress fibres and maturation of focal adhesions (FAs). Conversely, loss of Lfc expression decreases RhoA activity, stress fibre formation and FA size, suggesting that Lfc is the major GEF downstream of FN-bound αvÎČ3 that controls RhoA activity. Mechanistically, FN-engaged αvÎČ3 integrin activates a kinase cascade involving MARK2 and MARK3, which in turn leads to phosphorylation of several phospho-sites on Lfc. In particular, S151 was identified as the main site involved in the regulation of Lfc localization and activity. Our findings indicate that activation of Lfc and RhoA is orchestrated in FN-adherent cells in an integrin-specific manner.Fil: Colo, Georgina Pamela. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - BahĂ­a Blanca. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca. Universidad Nacional del Sur. Instituto de Investigaciones BioquĂ­micas de BahĂ­a Blanca; ArgentinaFil: Seiwert, Andrea. Max Planck Institute Of Biochemistry.; AlemaniaFil: Haga, Raquel B.. Max Planck Institute Of Biochemistry.; Alemani

    Homologous Recombination under the Single-Molecule Fluorescence Microscope

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    Homologous recombination (HR) is a complex biological process and is central to meiosis and for repair of DNA double-strand breaks. Although the HR process has been the subject of intensive study for more than three decades, the complex protein–protein and protein–DNA interactions during HR present a significant challenge for determining the molecular mechanism(s) of the process. This knowledge gap is largely because of the dynamic interactions between HR proteins and DNA which is difficult to capture by routine biochemical or structural biology methods. In recent years, single-molecule fluorescence microscopy has been a popular method in the field of HR to visualize these complex and dynamic interactions at high spatiotemporal resolution, revealing mechanistic insights of the process. In this review, we describe recent efforts that employ single-molecule fluorescence microscopy to investigate protein–protein and protein–DNA interactions operating on three key DNA-substrates: single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), and four-way DNA called Holliday junction (HJ). We also outline the technological advances and several key insights revealed by these studies in terms of protein assembly on these DNA substrates and highlight the foreseeable promise of single-molecule fluorescence microscopy in advancing our understanding of homologous recombination

    Robust sound source mapping using three-layered selective audio rays for mobile robots

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    © 2016 IEEE. This paper investigates sound source mapping in a real environment using a mobile robot. Our approach is based on audio ray tracing which integrates occupancy grids and sound source localization using a laser range finder and a microphone array. Previous audio ray tracing approaches rely on all observed rays and grids. As such observation errors caused by sound reflection, sound occlusion, wall occlusion, sounds at misdetected grids, etc. can significantly degrade the ability to locate sound sources in a map. A three-layered selective audio ray tracing mechanism is proposed in this work. The first layer conducts frame-based unreliable ray rejection (sensory rejection) considering sound reflection and wall occlusion. The second layer introduces triangulation and audio tracing to detect falsely detected sound sources, rejecting audio rays associated to these misdetected sounds sources (short-term rejection). A third layer is tasked with rejecting rays using the whole history (long-term rejection) to disambiguate sound occlusion. Experimental results under various situations are presented, which proves the effectiveness of our method
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