6,491 research outputs found

    Working with the patient and clinical community to deliver clinical research in cystic fibrosis. James Lind CF Phase II

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    This is a protocol which sets out the aims, objectives and commitments of the second phase of the James Lind Alliance Priority Setting Partnership in Cystic Fibrosis and the basic roles and responsibilities of the partners therein. The James Lind Alliance Priority Setting Partnership in cystic fibrosis was carried out in 2016 using a robust and widely accepted methodology to develop the top 10 questions for clinical research in CF, through discussions with both the clinical and patient community. We now aim to explore four of the top ten questions from this process and develop them into a series of testable hypotheses for clinical research. Where the hypothesis will be tested in a clinical trial, we will develop a PICO question for each hypothesis (Population, Intervention, Comparator & Outcome). We will use online surveys and focus groups to achieve our aim

    New F-19 NMR methodology reveals structures of molecules in complex mixtures of fluorinated compounds

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    Although the number of natural fluorinated compounds is very small, fluorinated pharmaceuticals and agrochemicals are numerous. (19)F NMR spectroscopy has a great potential for the structure elucidation of fluorinated organic molecules, starting with their production by chemical or chemoenzymatic reactions, through monitoring their structural integrity, to their biotic and abiotic transformation and ultimate degradation in the environment. Additionally, choosing to incorporate (19)F into any organic molecule opens a convenient route to study reaction mechanisms and kinetics. Addressing limitations of the existing (19)F NMR techniques, we have developed methodology that uses (19)F as a powerful spectroscopic spy to study mixtures of fluorinated molecules. The proposed (19)F-centred NMR analysis utilises the substantial resolution and sensitivity of (19)F to obtain a large number of NMR parameters, which enable structure determination of fluorinated compounds without the need for their separation or the use of standards. Here we illustrate the (19)F-centred structure determination process and demonstrate its power by successfully elucidating the structures of chloramination disinfectant by-products of a single mono-fluorinated phenolic compound, which would have been impossible otherwise. This novel NMR approach for the structure elucidation of molecules in complex mixtures represents a major contribution towards the analysis of chemical and biological processes involving fluorinated compounds

    dc readout experiment at the Caltech 40m prototype interferometer

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    The Laser Interferometer Gravitational Wave Observatory (LIGO) operates a 40m prototype interferometer on the Caltech campus. The primary mission of the prototype is to serve as an experimental testbed for upgrades to the LIGO interferometers and for gaining experience with advanced interferometric techniques, including detuned resonant sideband extraction (i.e. signal recycling) and dc readout (optical homodyne detection). The former technique will be employed in Advanced LIGO, and the latter in both Enhanced and Advanced LIGO. Using dc readout for gravitational wave signal extraction has several technical advantages, including reduced laser and oscillator noise couplings as well as reduced shot noise, when compared to the traditional rf readout technique (optical heterodyne detection) currently in use in large-scale ground-based interferometric gravitational wave detectors. The Caltech 40m laboratory is currently prototyping a dc readout system for a fully suspended interferometric gravitational wave detector. The system includes an optical filter cavity at the interferometer's output port, and the associated controls and optics to ensure that the filter cavity is optimally coupled to the interferometer. We present the results of measurements to characterize noise couplings in rf and dc readout using this system

    The TREC2001 video track: information retrieval on digital video information

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    The development of techniques to support content-based access to archives of digital video information has recently started to receive much attention from the research community. During 2001, the annual TREC activity, which has been benchmarking the performance of information retrieval techniques on a range of media for 10 years, included a ”track“ or activity which allowed investigation into approaches to support searching through a video library. This paper is not intended to provide a comprehensive picture of the different approaches taken by the TREC2001 video track participants but instead we give an overview of the TREC video search task and a thumbnail sketch of the approaches taken by different groups. The reason for writing this paper is to highlight the message from the TREC video track that there are now a variety of approaches available for searching and browsing through digital video archives, that these approaches do work, are scalable to larger archives and can yield useful retrieval performance for users. This has important implications in making digital libraries of video information attainable

    Diversity in the structures and ligand binding sites of nematode fatty acid and retinol binding proteins revealed by Na-FAR-1 from Necator americanus

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    Fatty acid and retinol binding proteins (FARs) comprise a family of unusual α-helix rich lipid binding proteins found exclusively in nematodes. They are secreted into host tissues by parasites of plants, animals and humans. The structure of a FAR protein from the free-living nematode Caenorhabditis elegans is available, but this protein (Ce-FAR-7) is from a subfamily of FARs that does not appear to be important at the host-parasite interface. We have therefore examined Na-FAR-1 from the blood-feeding intestinal parasite of humans, Necator americanus . The three dimensional structure of Na-FAR-1 in its ligand-free and ligand-bound forms, determined by nuclear magnetic resonance spectroscopy (NMR) and X-ray crystallography, respectively, reveals an a-helical fold similar to Ce-FAR-7, but Na-FAR-1 possesses a larger and more complex internal ligand binding cavity and an additional C-terminal a-helix. Titration of apo -Na-FAR-1 with oleic acid, analysed by NMR chemical shift perturbation, reveals that at least four distinct protein:ligand complexes can be formed. Na-FAR-1, and possibly other FARs, may have a wider repertoire for hydrophobic ligand binding, as confirmed here by our finding that a range of neutral and polar lipids co-purify with the bacterial recombinant protein. Finally, we show by immunohistochemistry that Na-FAR-1 is present in adult worms with a tissue distribution indicative of possible roles in nutrient acquisition by the parasite and in reproduction in the male

    Discovery of a Bright Field Methane (T-type) Brown Dwarf by 2MASS

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    We report the discovery of a bright (J = 13.83±\pm0.03) methane brown dwarf, or T dwarf, by the Two Micron All Sky Survey. This object, 2MASSI J0559191-140448, is the first brown dwarf identified by the newly commissioned CorMASS instrument mounted on the Palomar 60-inch Telescope. Near-infrared spectra from 0.9 - 2.35 \micron show characteristic CH4_4 bands at 1.1, 1.3, 1.6, and 2.2 \micron, which are significantly shallower than those seen in other T dwarfs discovered to date. Coupled with the detection of an FeH band at 0.9896 \micron and two sets of K I doublets at J-band, we propose that 2MASS J0559-14 is a warm T dwarf, close to the transition between L and T spectral classes. The brightness of this object makes it a good candidate for detailed investigation over a broad wavelength regime and at higher resolution.Comment: 21 pages, 3 figures, 2 tables, accepted to AJ for publication August 200

    Working with the patient and clinical community to deliver clinical research in cystic fibrosis: James Lind CF Phase II

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    This is a protocol which sets out the aims, objectives and commitments of the second phase of the James Lind Alliance Priority Setting Partnership in Cystic Fibrosis and the basic roles and responsibilities of the partners therein. The James Lind Alliance Priority Setting Partnership in cystic fibrosis was carried out in 2016 using a robust and widely accepted methodology to develop the top 10 questions for clinical research in CF, through discussions with both the clinical and patient community.We now aim to explore four of the top ten questions from this process and develop them into a series of testable hypotheses for clinical research. Where the hypothesis will be tested in a clinical trial, we will develop a PICO question for each hypothesis (Population, Intervention, Comparator & Outcome). We will use online surveys and focus groups to achieve our aim
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