433 research outputs found

    Motion-base simulator study of control of an externally blown flap STOL transport aircraft after failure of an outboard engine during landing approach

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    A moving-base simulator investigation of the problems of recovery and landing of a STOL aircraft after failure of an outboard engine during final approach was made. The approaches were made at 75 knots along a 6 deg glide slope. The engine was failed at low altitude and the option to go around was not allowed. The aircraft was simulated with each of three control systems, and it had four high-bypass-ratio fan-jet engines exhausting against large triple-slotted wing flaps to produce additional lift. A virtual-image out-the-window television display of a simulated STOL airport was operating during part of the investigation. Also, a simple heads-up flight director display superimposed on the airport landing scene was used by the pilots to make some of the recoveries following an engine failure. The results of the study indicated that the variation in visual cues and/or motion cues had little effect on the outcome of a recovery, but they did have some effect on the pilot's response and control patterns

    A Modern Mode of Activation for Nucleic Acid Enzymes

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    Through evolution, enzymes have developed subtle modes of activation in order to ensure the sufficiently high substrate specificity required by modern cellular metabolism. One of these modes is the use of a target-dependent module (i.e. a docking domain) such as those found in signalling kinases. Upon the binding of the target to a docking domain, the substrate is positioned within the catalytic site. The prodomain acts as a target-dependent module switching the kinase from an off state to an on state. As compared to the allosteric mode of activation, there is no need for the presence of a third partner. None of the ribozymes discovered to date have such a mode of activation, nor does any other known RNA. Starting from a specific on/off adaptor for the hepatitis delta virus ribozyme, that differs but has a mechanism reminiscent of this signalling kinase, we have adapted this mode of activation, using the techniques of molecular engineering, to both catalytic RNAs and DNAs exhibiting various activities. Specifically, we adapted three cleaving ribozymes (hepatitis delta virus, hammerhead and hairpin ribozymes), a cleaving 10-23 deoxyribozyme, a ligating hairpin ribozyme and an artificially selected capping ribozyme. In each case, there was a significant gain in terms of substrate specificity. Even if this mode of control is unreported for natural catalytic nucleic acids, its use needs not be limited to proteinous enzymes. We suggest that the complexity of the modern cellular metabolism might have been an important selective pressure in this evolutionary process

    SDSS J0806+2006 and SDSS J1353+1138: Two New Gravitationally Lensed Quasars from the Sloan Digital Sky Survey

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    We report the discoveries of two, two-image gravitationally lensed quasars selected from the Sloan Digital Sky Survey: SDSS J0806+2006 at z_s=1.540 and SDSS J1353+1138 at z_s=1.629 with image separations of 1.40" and 1.41" respectively. Spectroscopic and optical/near-infrared imaging follow-up observations show that the quasar images have identical redshifts and possess extended objects between the images that are likely to be lens galaxies at z_l~0.6 in SDSS J0806+2006 and z_l~0.3 in SDSS J1353+1138. The field of SDSS J0806+2006 contains several nearby galaxies that may significantly perturb the system, and SDSS J1353+1138 has an extra component near its Einstein ring that is probably a foreground star. Simple mass models with reasonable parameters reproduce the quasar positions and fluxes of both systems.Comment: 27 pages, 7 figures, The Astronomical Journal accepte

    The Lyman Alpha Forest in the Spectra of QSOs

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    Observations of redshifted Lyman alpha forest absorption in the spectra of quasistellar objects (QSOs) provide a highly sensitive probe of the distribution of gaseous matter in the universe. Over the past two decades optical spectroscopy with large ground-based telescopes, and more recently ultraviolet spectroscopy from space have yielded a wealth of information on what appears to be a gaseous, photoionized intergalactic medium, partly enriched by the products of stellar nucleosynthesis, residing in coherent structures over many hundreds of kiloparsecs. Recent progress with cosmological hydro-simulations based on hierarchical structure formation models has led to important insights into the physical structures giving rise to the forest. If these ideas are correct, a truely inter- and proto-galactic medium [at high redshift (z ~ 3), the main repository of baryons] collapses under the influence of dark matter gravity into flattened or filamentary structures, which are seen in absorption against background QSOs. With decreasing redshift, galaxies forming in the denser regions, may contribute an increasing part of the Lyman alpha absorption cross-section. Comparisons between large data samples from the new generation of telescopes and artificial Lyman alpha forest spectra from cosmological simulations promise to become a useful cosmological tool.Comment: latex plus three postscript figures, uses psfig,sty; Annual Review of Astronomy and Astrophysics 1998, vol. 36 (in press

    Chronic Respiratory Aeroallergen Exposure in Mice Induces Epithelial-Mesenchymal Transition in the Large Airways

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    Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM) extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1) levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA) and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease

    Subtle effects of environmental stress observed in the early life stages of the Common frog, Rana temporaria

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    Worldwide amphibian populations are declining due to habitat loss, disease and pollution. Vulnerability to environmental contaminants such as pesticides will be dependent on the species, the sensitivity of the ontogenic life stage and hence the timing of exposure and the exposure pathway. Herein we investigated the biochemical tissue ‘fingerprint’ in spawn and early-stage tadpoles of the Common frog, Rana temporaria, using attenuated total reflection- Fourier-transform infrared (ATR-FTIR) spectroscopy with the objective of observing differences in the biochemical constituents of the respective amphibian tissues due to varying water quality in urban and agricultural ponds. Our results demonstrate that levels of stress (marked by biochemical constituents such as glycogen that are involved in compensatory metabolic mechanisms) can be observed in tadpoles present in the pond most impacted by pollution (nutrients and pesticides), but large annual variability masked any inter-site differences in the frog spawn. ATR-FTIR spectroscopy is capable of detecting differences in tadpoles that are present in selected ponds with different levels of environmental perturbation and thus serves as a rapid and cost effective tool in assessing stress-related effects of pollution in a vulnerable class of organism

    Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach

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    Understanding the biological factors that are characteristic of metastasis in melanoma remains a key approach to improving treatment. In this study, we seek to identify a gene signature of metastatic melanoma. We configured a new network-based computational pipeline, combined with a machine learning method, to mine publicly available transcriptomic data from melanoma patient samples. Our method is unbiased and scans a genome-wide protein-protein interaction network using a novel formulation for network scoring. Using this, we identify the most influential, differentially expressed nodes in metastatic as compared to primary melanoma. We evaluated the shortlisted genes by a machine learning method to rank them by their discriminatory capacities. From this, we identified a panel of 6 genes, ALDH1A1, HSP90AB1, KIT, KRT16, SPRR3 and TMEM45B whose expression values discriminated metastatic from primary melanoma (87% classification accuracy). In an independent transcriptomic data set derived from 703 primary melanomas, we showed that all six genes were significant in predicting melanoma specific survival (MSS) in a univariate analysis, which was also consistent with AJCC staging. Further, 3 of these genes, HSP90AB1, SPRR3 and KRT16 remained significant predictors of MSS in a joint analysis (HR = 2.3, P = 0.03) although, HSP90AB1 (HR = 1.9, P = 2 × 10−4) alone remained predictive after adjusting for clinical predictors
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