423 research outputs found

    Application of active controls technology to aircraft bide smoothing systems

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    A critical review of past efforts in the design and testing of ride smoothing and gust alleviation systems is presented. Design trade offs involving sensor types, choice of feedback loops, human comfort, and aircraft handling-qualities criteria are discussed. Synthesis of a system designed to employ direct-lift and side-force producing surfaces is reported. Two STOL aircraft and an executive transport are considered. Theoretically predicted system performance is compared with hybrid simulation and flight test data. Pilot opinion rating, pilot workload, and passenger comfort rating data for the basic and augmented aircraft are included

    Accountability by Design: Moving Primary Care Reform Ahead in Alberta

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    Health-care reform is perennially popular in Alberta, but reality doesn’t match the rhetoric. Government has invested more than $700 million in Primary Care Networks — with little beyond anecdotal evidence of the value achieved with this investment. As the province redirects primary care to Family Care Clinics, the authors assert that simply tinkering with one part of the system is not the answer: health care must change on a system-wide basis. Drawing on the experiences of frontline staff and a rich body of literature, the authors present their vision for integrated team-based primary care, designed to be accountable to meet the needs of populations. This will require governance that makes primary care the hub of the system, and brings together government and health-services leadership to support the integration of primary and specialty care. There are shared accountabilities for achieving primary care that exhibits the attributes of high performing primary care systems, and these exist at multiple levels, from individuals seeking primary care, up to and including government. The authors make these accountabilities explicit, and outline strategies to secure their achievement that include system redesign, service delivery redesign and payment reform. All of this demands whole-system reform focused on primary care, and it won’t be easy. There are plenty of vested interests at stake, and a truly transformative vision requires buy-in at every level. However, Alberta’s rapidly growing and aging population makes it more urgent than ever to realize such a vision. This paper offers guidelines to spark the fresh thinking required

    A little data goes a long way: automating seismic phase arrival picking at Nabro Volcano with transfer learning

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    Supervised deep learning models have become a popular choice for seismic phase arrival detection. However, they do not always perform well on out-of-distribution data and require large training sets to aid generalization and prevent overfitting. This can present issues when using these models in new monitoring settings. In this work, we develop a deep learning model for automating phase arrival detection at Nabro volcano using a limited amount of training data (2,498 event waveforms recorded over 35 days) through a process known as transfer learning. We use the feature extraction layers of an existing, extensively trained seismic phase picking model to form the base of a new all-convolutional model, which we call U-GPD. We demonstrate that transfer learning reduces overfitting and model error relative to training the same model from scratch, particularly for small training sets (e.g., 500 waveforms). The new U-GPD model achieves greater classification accuracy and smaller arrival time residuals than off-the-shelf applications of two existing, extensively-trained baseline models for a test set of 800 event and noise waveforms from Nabro volcano. When applied to 14 months of continuous Nabro data, the new U-GPD model detects 31,387 events with at least four P-wave arrivals and one S-wave arrival, which is more than the original base model (26,808 events) and our existing manual catalog (2,926 events), with smaller location errors. The new model is also more efficient when applied as a sliding window, processing 14 months of data from seven stations in less than 4 h on a single graphics processing unit

    Phenotyping progenies for complex architectural traits: a strategy for 1-year-old apple trees (Malus x domestica Borkh.)

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    International audienceThe aim of this study was to define a methodology for describing architectural traits in a quantitative way on tree descendants. Our strategy was to collect traits related to both tree structural organization, resulting from growth and branching, and tree form and then to select among these traits relevant descriptors on the basis of their genetic parameters. Because the complexity of tree architecture increases with tree age, we chose to describe the trees in the early stages of development. The study was carried out on a 1-year-old apple progeny derived from two parent cultivars with contrasted architecture. A large number of variables were collected at different positions and scales within the trees. Broad-sense heritability and genetic correlations were estimated and the within tree variability was analyzed for variables measured on long sylleptic axillary shoots (LSAS). These results were combined to select heritable and not correlated variables. Finally, the selection of variables proposed combines topological with geometric traits measured on both trunks and LSAS: (1) on the trunk, mean internode length, and number of sylleptic axillary shoots; (2) on axillary shoots, conicity, bending, and number of sylleptic axillary shoots born at order 3. The trees of the progeny were partitioned on the basis of these variables. The putative agronomic interest of the selected variables with respect to the subsequent tree development is discussed

    Kinome-wide interaction modelling using alignment-based and alignment-independent approaches for kinase description and linear and non-linear data analysis techniques

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    <p>Abstract</p> <p>Background</p> <p>Protein kinases play crucial roles in cell growth, differentiation, and apoptosis. Abnormal function of protein kinases can lead to many serious diseases, such as cancer. Kinase inhibitors have potential for treatment of these diseases. However, current inhibitors interact with a broad variety of kinases and interfere with multiple vital cellular processes, which causes toxic effects. Bioinformatics approaches that can predict inhibitor-kinase interactions from the chemical properties of the inhibitors and the kinase macromolecules might aid in design of more selective therapeutic agents, that show better efficacy and lower toxicity.</p> <p>Results</p> <p>We applied proteochemometric modelling to correlate the properties of 317 wild-type and mutated kinases and 38 inhibitors (12,046 inhibitor-kinase combinations) to the respective combination's interaction dissociation constant (K<sub>d</sub>). We compared six approaches for description of protein kinases and several linear and non-linear correlation methods. The best performing models encoded kinase sequences with amino acid physico-chemical z-scale descriptors and used support vector machines or partial least- squares projections to latent structures for the correlations. Modelling performance was estimated by double cross-validation. The best models showed high predictive ability; the squared correlation coefficient for new kinase-inhibitor pairs ranging P<sup>2 </sup>= 0.67-0.73; for new kinases it ranged P<sup>2</sup><sub>kin </sub>= 0.65-0.70. Models could also separate interacting from non-interacting inhibitor-kinase pairs with high sensitivity and specificity; the areas under the ROC curves ranging AUC = 0.92-0.93. We also investigated the relationship between the number of protein kinases in the dataset and the modelling results. Using only 10% of all data still a valid model was obtained with P<sup>2 </sup>= 0.47, P<sup>2</sup><sub>kin </sub>= 0.42 and AUC = 0.83.</p> <p>Conclusions</p> <p>Our results strongly support the applicability of proteochemometrics for kinome-wide interaction modelling. Proteochemometrics might be used to speed-up identification and optimization of protein kinase targeted and multi-targeted inhibitors.</p

    XMPP for cloud computing in bioinformatics supporting discovery and invocation of asynchronous web services

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    Background: Life sciences make heavily use of the web for both data provision and analysis. However, the increasing amount of available data and the diversity of analysis tools call for machine accessible interfaces in order to be effective. HTTP-based Web service technologies, like the Simple Object Access Protocol (SOAP) and REpresentational State Transfer (REST) services, are today the most common technologies for this in bioinformatics. However, these methods have severe drawbacks, including lack of discoverability, and the inability for services to send status notifications. Several complementary workarounds have been proposed, but the results are ad-hoc solutions of varying quality that can be difficult to use. Results: We present a novel approach based on the open standard Extensible Messaging and Presence Protocol (XMPP), consisting of an extension (IO Data) to comprise discovery, asynchronous invocation, and definition of data types in the service. That XMPP cloud services are capable of asynchronous communication implies that clients do not have to poll repetitively for status, but the service sends the results back to the client upon completion. Implementations for Bioclipse and Taverna are presented, as are various XMPP cloud services in bio- and cheminformatics. Conclusion: XMPP with its extensions is a powerful protocol for cloud services that demonstrate several advantages over traditional HTTP-based Web services: 1) services are discoverable without the need of an external registry, 2) asynchronous invocation eliminates the need for ad-hoc solutions like polling, and 3) input and output types defined in the service allows for generation of clients on the fly without the need of an external semantics description. The many advantages over existing technologies make XMPP a highly interesting candidate for next generation online services in bioinformatics

    Enzymatic Analysis of Recombinant Japanese Encephalitis Virus NS2B(H)-NS3pro Protease with Fluorogenic Model Peptide Substrates

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    Background Japanese encephalitis virus (JEV), a member of the Flaviviridae family, causes around 68,000 encephalitis cases annually, of which 20–30% are fatal, while 30–50% of the recovered cases develop severe neurological sequelae. Specific antivirals for JEV would be of great importance, particularly in those cases where the infection has become persistent. Being indispensable for flaviviral replication, the NS2B-NS3 protease is a promising target for design of anti-flaviviral inhibitors. Contrary to related flaviviral proteases, the JEV NS2B-NS3 protease is structurally and mechanistically much less characterized. Here we aimed at establishing a straightforward procedure for cloning, expression, purification and biochemical characterization of JEV NS2B(H)-NS3pro protease. Methodology/Principal Findings The full-length sequence of JEV NS2B-NS3 genotype III strain JaOArS 982 was obtained as a synthetic gene. The sequence of NS2B(H)-NS3pro was generated by splicing by overlap extension PCR (SOE-PCR) and cloned into the pTrcHisA vector. Hexahistidine-tagged NS2B(H)-NS3pro, expressed in E. coli as soluble protein, was purified to &gt;95% purity by a single-step immobilized metal affinity chromatography. SDS-PAGE and immunoblotting of the purified enzyme demonstrated NS2B(H)-NS3pro precursor and its autocleavage products, NS3pro and NS2B(H), as 36, 21, and 10 kDa bands, respectively. Kinetic parameters, Km and kcat, for fluorogenic protease model substrates, Boc-GRR-amc, Boc-LRR-amc, Ac-nKRR-amc, Bz-nKRR-amc, Pyr-RTKR-amc and Abz-(R)4SAG-nY-amide, were obtained using inner filter effect correction. The highest catalytic efficiency kcat/Km was found for Pyr-RTKR-amc (kcat/Km: 1962.96±85.0 M−1 s−1) and the lowest for Boc-LRR-amc (kcat/Km: 3.74±0.3 M−1 s−1). JEV NS3pro is inhibited by aprotinin but to a lesser extent than DEN and WNV NS3pro. Conclusions/Significance A simplified procedure for the cloning, overexpression and purification of the NS2B(H)-NS3pro was established which is generally applicable to other flaviviral proteases. Kinetic parameters obtained for a number of model substrates and inhibitors, are useful for the characterization of substrate specificity and eventually for the design of high-throughput assays aimed at antiviral inhibitor discovery

    Modelling of the effect of ELMs on fuel retention at the bulk W divertor of JET

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    Effect of ELMs on fuel retention at the bulk W target of JET ITER-Like Wall was studied with multi-scale calculations. Plasma input parameters were taken from ELMy H-mode plasma experiment. The energetic intra-ELM fuel particles get implanted and create near-surface defects up to depths of few tens of nm, which act as the main fuel trapping sites during ELMs. Clustering of implantation-induced vacancies were found to take place. The incoming flux of inter-ELM plasma particles increases the different filling levels of trapped fuel in defects. The temperature increase of the W target during the pulse increases the fuel detrapping rate. The inter-ELM fuel particle flux refills the partially emptied trapping sites and fills new sites. This leads to a competing effect on the retention and release rates of the implanted particles. At high temperatures the main retention appeared in larger vacancy clusters due to increased clustering rate

    On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

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    A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)
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