1,515 research outputs found

    Fixed base simulator study of an externally blown flap STOL transport airplane during approach and landing

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    A fixed-base simulator study was conducted to determine the flight characteristics of a representative STOL transport having a high wing and equipped with an external-flow jet flap in combination with four high-bypass-ratio fan-jet engines during the approach and landing. Real-time digital simulation techniques were used. The computer was programed with equations of motion for six degrees of freedom and the aerodynamic inputs were based on measured wind-tunnel data. A visual display of a STOL airport was provided for simulation of the flare and touchdown characteristics. The primary piloting task was an instrument approach to a breakout at a 200-ft ceiling with a visual landing

    Handling qualities of a wide-body transport airplane utilizing Pitch Active Control Systems (PACS) for relaxed static stability application

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    Piloted simulation studies have been conducted to evaluate the effectiveness of two pitch active control systems (PACS) on the flying qualities of a wide-body transport airplane when operating at negative static margins. These two pitch active control systems consisted of a simple 'near-term' PACS and a more complex 'advanced' PACS. Eight different flight conditions, representing the entire flight envelope, were evaluated with emphasis on the cruise flight conditions. These studies were made utilizing the Langley Visual/Motion Simulator (VMS) which has six degrees of freedom. The simulation tests indicated that (1) the flying qualities of the baseline aircraft (PACS off) for the cruise and other high-speed flight conditions were unacceptable at center-of-gravity positions aft of the neutral static stability point; (2) within the linear static stability flight envelope, the near-term PACS provided acceptable flying qualities for static stabilty margins to -3 percent; and (3) with the advanced PACS operative, the flying qualities were demonstrated to be good (satisfactory to very acceptable) for static stabilty margins to -20 percent

    Sequence similarity is more relevant than species specificity in probabilistic backtranslation

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    BACKGROUND: Backtranslation is the process of decoding a sequence of amino acids into the corresponding codons. All synthetic gene design systems include a backtranslation module. The degeneracy of the genetic code makes backtranslation potentially ambiguous since most amino acids are encoded by multiple codons. The common approach to overcome this difficulty is based on imitation of codon usage within the target species. RESULTS: This paper describes EasyBack, a new parameter-free, fully-automated software for backtranslation using Hidden Markov Models. EasyBack is not based on imitation of codon usage within the target species, but instead uses a sequence-similarity criterion. The model is trained with a set of proteins with known cDNA coding sequences, constructed from the input protein by querying the NCBI databases with BLAST. Unlike existing software, the proposed method allows the quality of prediction to be estimated. When tested on a group of proteins that show different degrees of sequence conservation, EasyBack outperforms other published methods in terms of precision. CONCLUSION: The prediction quality of a protein backtranslation methis markedly increased by replacing the criterion of most used codon in the same species with a Hidden Markov Model trained with a set of most similar sequences from all species. Moreover, the proposed method allows the quality of prediction to be estimated probabilistically

    Care during the third stage of labour: obstetricians views and practice in an Albanian maternity hospital

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    <p>Abstract</p> <p>Background</p> <p>Relatively little is known about current practice during the third stage of labour in low and middle income countries. We conducted a survey of attitudes and an audit of practice in a large maternity hospital in Albania.</p> <p>Methods</p> <p>Survey of 35 obstetricians and audit of practice during the third stage was conducted in July 2008 at a tertiary referral hospital in Tirana. The survey questionnaire was self completed. Responses were anonymous. For the audit, information collected included time of administration of the uterotonic drug, gestation at birth, position of the baby before cord clamping, cord traction, and need for resuscitation.</p> <p>Results</p> <p>77% (27/35) of obstetricians completed the questionnaire, of whom 78% (21/27) reported always or usually using active management, and 22% (6/27) always or usually using physiological care. When using active management: 56% (15/27) gave the uterotonic after cord clamping; intravenous oxytocin was almost always the drug used; and 71% (19/27) clamped the cord within one minute. For physiological care: 42% (8/19) clamped the cord within 20 seconds, and 96% (18/19) within one minute. 93% would randomise women to a trial of early versus late cord clamping.</p> <p>Practice was observed for 156 consecutive births, of which 26% (42/156) were by caesarean section. A prophylactic uterotonic was used for 87% (137/156): this was given after cord clamping for 55% (75/137), although timing of administration was not recorded for 21% (29/137). For 85% of births (132/156) cord clamping was within 20 seconds, and for all babies it was within 50 seconds. Controlled cord traction was used for 49% (76/156) of births.</p> <p>Conclusions</p> <p>Most obstetricians reported always or usually using active management for the third stage of labour. For timing and choice of the uterotonic drug, reported practice was similar to actual practice. Although some obstetricians reported they waited longer than one minute before clamping the cord, this was not observed in practice. Controlled cord traction was used for half the births.</p

    Upper-body resistance training following soccer match play: Compatible, complementary, or contraindicated?

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    Purpose: During heavily congested schedules, professional soccer players can experience exacerbated fatigue responses, which are thought to contribute to an increased risk of injury. Given that match-induced residual fatigue can last up to 72 hours, many coaches naturally prioritize recovery in the days immediately following match day. While it is intuitive for coaches and training staff to decrease the amount of auxiliary training practices to focus on recovery, prescribing upper-body resistance training on the day after match play has recently emerged as a specific training modality in this context. While these sessions may be implemented to increase training stimulus, there are limited data available regarding the efficacy of such a practice to improve recovery kinetics. Methods: In this narrative review, the authors look at the theoretical implications of performing upper-body resistance training on the day after match play on the status of various physiological and psychological systems, including neuromuscular, metabolic, hormonal, perceptual, and immunological recovery. Results: The available evidence suggests that in most cases this practice, as currently implemented (ie, low volume, low intensity), is unlikely to be complementary (ie, does not accelerate recovery) but is potentially compatible (ie, does not impair recovery). Conclusion: Overall, because the perception of such sessions may be player dependent, their programming requires an individualized approach and should take into account match dynamics (eg, fixture scheduling, playing time, travel)

    Conserving biodiversity in production landscapes

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    Alternative land uses make different contributions to the conservation of biodiversity and have different implementation and management costs. Conservation planning analyses to date have generally assumed that land is either protected or unprotected and that the unprotected portion does not contribute to conservation goals. We develop and apply a new planning approach that explicitly accounts for the contribution of a diverse range of land uses to achieving conservation goals. Using East Kalimantan (Indonesian Borneo) as a case study, we prioritize investments in alternative conservation strategies and account for the relative contribution of land uses ranging from production forest to well-managed protected areas. We employ data on the distribution of mammals and assign species-specific conservation targets to achieve equitable protection by accounting for life history characteristics and home range sizes. The relative sensitivity of each species to forest degradation determines the contribution of each land use to achieving targets. We compare the cost effectiveness of our approach to a plan that considers only the contribution of protected areas to biodiversity conservation, and to a plan that assumes that the cost of conservation is represented by only the opportunity costs of conservation to the timber industry. Our preliminary results will require further development and substantial stakeholder engagement prior to implementation; nonetheless we reveal that, by accounting for the contribution of unprotected land, we can obtain more refined estimates of the costs of conservation. Using traditional planning approaches would overestimate the cost of achieving the conservation targets by an order of magnitude. Our approach reveals not only where to invest, but which strategies to invest in, in order to effectively and efficiently conserve biodiversity. Copyright ESA. All rights reserved

    Bioactive Recombinant Human Oncostatin M for NMR-Based Screening in Drug Discovery

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    Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 μM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening

    Change in Terrestrial Human Footprint Drives Continued Loss of Intact Ecosystems

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    Human pressure mapping is important for understanding humanity's role in shaping Earth's patterns and processes. We provide the latest maps of the terrestrial human footprint and provide an assessment of change in human pressure across Earth. Between 2000 and 2013, 1.9 million km2 of land relatively free of human disturbance became highly modified. Our results show that humanity's footprint is eroding Earth's last intact ecosystems and that greater efforts are urgently needed to retain them

    Selective Constraints on Amino Acids Estimated by a Mechanistic Codon Substitution Model with Multiple Nucleotide Changes

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    Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code, and the strength of selective constraints against amino acid replacements can be tailored to a given gene. First, selective constraints averaged over proteins are estimated by maximizing the likelihood of each 1-PAM matrix of empirical amino acid (JTT, WAG, and LG) and codon (KHG) substitution matrices. Then, selective constraints specific to given proteins are approximated as a linear function of those estimated from the empirical substitution matrices. Akaike information criterion (AIC) values indicate that a model allowing multiple nucleotide changes fits the empirical substitution matrices significantly better. Also, the ML estimates of transition-transversion bias obtained from these empirical matrices are not so large as previously estimated. The selective constraints are characteristic of proteins rather than species. However, their relative strengths among amino acid pairs can be approximated not to depend very much on protein families but amino acid pairs, because the present model, in which selective constraints are approximated to be a linear function of those estimated from the JTT/WAG/LG/KHG matrices, can provide a good fit to other empirical substitution matrices including cpREV for chloroplast proteins and mtREV for vertebrate mitochondrial proteins. The present codon-based model with the ML estimates of selective constraints and with adjustable mutation rates of nucleotide would be useful as a simple substitution model in ML and Bayesian inferences of molecular phylogenetic trees, and enables us to obtain biologically meaningful information at both nucleotide and amino acid levels from codon and protein sequences.Comment: Table 9 in this article includes corrections for errata in the Table 9 published in 10.1371/journal.pone.0017244. Supporting information is attached at the end of the article, and a computer-readable dataset of the ML estimates of selective constraints is available from 10.1371/journal.pone.001724
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