1,762 research outputs found
A Research Agenda for Linked Closed Data
While it is preferable that Linked Data is published without access or licence restrictions, there will always remain certain datasets which, perhaps due to financial considerations, cannot be published as Linked Open Data. If these valuable datasets do join the Web of Linked Data, it will be as Linked Closed Data - Linked Data with access and license restrictions. In this paper, we outline a research agenda for Linked Closed Data that considers the effects that access and license restrictions may have on the Web of Linked Data. If implemented poorly, access restrictions have the potential to break URI resolvability, but even when implemented well, we can expect them to affect dataset selection processes and inter-dataset link creation rates. Additionally, there remains the technical challenge of developing and standardising access restriction and automated payment techniques for the Web of Linked Data
Extravehicular activity at geosynchronous earth orbit
The basic contract to define the system requirements to support the Advanced Extravehicular Activity (EVA) has three phases: EVA in geosynchronous Earth orbit; EVA in lunar base operations; and EVA in manned Mars surface exploration. The three key areas to be addressed in each phase are: environmental/biomedical requirements; crew and mission requirements; and hardware requirements. The structure of the technical tasks closely follows the structure of the Advanced EVA studies for the Space Station completed in 1986
Advanced extravehicular activity systems requirements definition study. Phase 2: Extravehicular activity at a lunar base
The focus is on Extravehicular Activity (EVA) systems requirements definition for an advanced space mission: remote-from-main base EVA on the Moon. The lunar environment, biomedical considerations, appropriate hardware design criteria, hardware and interface requirements, and key technical issues for advanced lunar EVA were examined. Six remote EVA scenarios (three nominal operations and three contingency situations) were developed in considerable detail
ENGLISH FOR UNI
ENGLISH FOR UNI
A website developed by Julia Miller, Richard Warner, Fiona Henderson, Kayoko Enomoto, Ben McCann, Wang LiJuan, Anne Harris, and Joseph Miller
Community Pediatrics and Growing Kids South Burlington An assessment of collaboration between area pediatricians and integrated services for families of young children in South Burlington, VT
Background: It is widely accepted for pediatric and family medicine practitioners to use developmental screening tools for effective identification of children who require additional support. A recent study in Pediatrics reported that between 2002 and 2009, the percentage of pediatricians using standardized screening tools for developmental delay increased from 23.0% to 47.7%. While improvement was found, less than half of pediatricians used these tools. In addition, it is known that early intervention for children requiring extra support is essential for preventing further delay in reaching milestones. Practitioners’ use of screening tools and their collaboration with their community resources can contribute to better delivery of these services and aid in children meeting developmental milestones.https://scholarworks.uvm.edu/comphp_gallery/1070/thumbnail.jp
Evolutionary expansion of the amidohydrolase superfamily in bacteria in response to the synthetic compounds molinate and diuron
The amidohydrolase superfamily has remarkable functional diversity, with considerable structural and functional annotation of known sequences. In microbes, the recent evolution of several members of this family to catalyze the breakdown of environmental xenobiotics is not well understood. An evolutionary transition from binuclear to mononuclear metal ion coordination at the active sites of these enzymes could produce large functional changes such as those observed in nature, but there are few clear examples available to support this hypothesis. To investigate the role of binuclear-mononuclear active-site transitions in the evolution of new function in this superfamily, we have characterized two recently evolved enzymes that catalyze the hydrolysis of the synthetic herbicides molinate (MolA) and phenylurea (PuhB). In this work, the crystal structures, mutagenesis, metal ion analysis, and enzyme kinetics of both MolA and PuhB establish that these enzymes utilize a mononuclear active site. However, bioinformatics and structural comparisons reveal that the closest putative ancestor of these enzymes had a binuclear active site, indicating that a binuclear-mononuclear transition has occurred. These proteins may represent examples of evolution modifying the characteristics of existing catalysts to satisfy new requirements, specifically, metal ion rearrangement leading to large leaps in activity that would not otherwise be possible
Use of bisulfite processing to generate high-β-O-4 content water-soluble lignosulfonates
This work was supported by EPSRC grants (EP/1518175), the Industrial Biotechnology Innovation Centre (IBioIC) (DMB Ph.D. studentship) and an EPSRC Doctoral Prize Fellowship (CSL).With lignin-first biorefineries likely to become a reality, controlled depolymerization of high-quality lignin streams to high value products has become a priority. Using bisulfite chemistry, access to a high-β-O-4 content water-soluble lignosulfonate has been achieved, allowing follow-on procedures in water to be conducted. We show that phenolic β-O-4 units preferential-ly react under acidic bisulfite conditions, whilst non-phenolic β-O-4 units react much more slowly. Exploiting this improved chemical understanding and inherent selectivity, a softwood lignosulfonate has been prepared in which phenolic β-O-4 α-sulfonation has occurred leaving significant native β-O-4 content. Use of an O-benzoylation protocol with lignin coupled with advanced 2D NMR methods has allowed detailed analysis of this and other commercial and industrial lignosulfonates. Conversion of the native β-O-4 to benzylic- oxidized β-O-4 units was followed by a selective reductive cleavage to give a premium aromatic monomer in pure form.Publisher PDFPeer reviewe
Solution structure of an ultra-stable single-chain insulin analog connects protein dynamics to a novel mechanism of receptor binding
Domain-minimized insulin receptors (IRs) have enabled crystallographic analysis of insulin-bound "micro-receptors." In such structures, the C-terminal segment of the insulin B chain inserts between conserved IR domains, unmasking an invariant receptor-binding surface that spans both insulin A and B chains. This "open" conformation not only rationalizes the inactivity of single-chain insulin (SCI) analogs (in which the A and B chains are directly linked), but also suggests that connecting (C) domains of sufficient length will bind the IR. Here, we report the high-resolution solution structure and dynamics of such an active SCI. The hormone's closed-to-open transition is foreshadowed by segmental flexibility in the native state as probed by heteronuclear NMR spectroscopy and multiple conformer simulations of crystallographic protomers as described in the companion article. We propose a model of the SCI's IR-bound state based on molecular-dynamics simulations of a micro-receptor complex. In this model, a loop defined by the SCI's B and C domains encircles the C-terminal segment of the IR α-subunit. This binding mode predicts a conformational transition between an ultra-stable closed state (in the free hormone) and an active open state (on receptor binding). Optimization of this switch within an ultra-stable SCI promises to circumvent insulin's complex global cold chain. The analog's biphasic activity, which serendipitously resembles current premixed formulations of soluble insulin and microcrystalline suspension, may be of particular utility in the developing world
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