1,315 research outputs found

    About the Portability of the DIDASS-Package (an IBM Implementation)

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    The aim of this paper is to point out the portability of the program package for linear multiple criteria reference point optimization. This should be understood as a step to improve the user-oriented feature of software developed at IIASA and can be an example for further implementations of the software on other computer systems. The actual reason for transferring the DIDASS-package to INSEE is the need for solving problems of medium- and long-term planning for the national economy of France which can be described by dynamic multiple-criteria linear programming models. This paper is an initial note on implementation problems. As soon as there is substantive application in INSEE it will be reported. We first describe the implementation problems, then the solutions and an hypothetical example to demonstrate the workability of the software

    Enhanced spontaneous activity of the mu opioid receptor by cysteine mutations: characterization of a tool for inverse agonist screening.

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    BACKGROUND: The concept of spontaneous- or constitutive-activity has become widely accepted and verified for numerous G protein-coupled receptors and this ligand-independent activity is also acknowledged to play a role in some pathologies. Constitutive activity has been reported for the mu opioid receptor. In some cases the increase in receptor basal activity was induced by chronic morphine administration suggesting that constitutive activity may contribute to the development of drug tolerance and dependence. Constitutively active mutants represent excellent tools for gathering information about the mechanisms of receptor activation and the possible physiological relevance of spontaneous receptor activity. The high basal level of activity of these mutants also allows for easier identification of inverse agonists, defined as ligands able to suppress spontaneous receptor activity, and leads to a better comprehension of their modulatory effects as well as possible in vivo use. RESULTS: Cysteines 348 and 353 of the human mu opioid receptor (hMOR) were mutated into alanines and Ala(348,353 )hMOR was stably expressed in HEK 293 cells. [(35)S] GTPÎłS binding experiments revealed that Ala(348,353 )hMOR basal activity was significantly higher when compared to hMOR, suggesting that the mutant receptor is constitutively active. [(35)S] GTPÎłS binding was decreased by cyprodime or CTOP indicating that both ligands have inverse agonist properties. All tested agonists exhibited binding affinities higher for Ala(348,353 )hMOR than for hMOR, with the exception of endogenous opioid peptides. Antagonist affinity remained virtually unchanged except for CTOP and cyprodime that bound the double mutant with higher affinities. The agonists DAMGO and morphine showed enhanced potency for the Ala(348,353 )hMOR receptor in [(35)S] GTPÎłS experiments. Finally, pretreatment with the antagonists naloxone, cyprodime or CTOP significantly increased Ala(348,353 )hMOR expression. CONCLUSION: Taken together our data indicate that the double C348/353A mutation results in a constitutively active conformation of hMOR that is still activated by agonists. This is the first report of a stable CAM of hMOR with the potential to screen for inverse agonists

    KLAST: fast and sensitive software to compare large genomic databanks on cloud

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    International audienceAs the genomic data generated by high throughput sequencing machines continue to exponentially grow, the need for very efficient bioinformatics tools to extract relevant knowledge from this mass of data doesn't weaken. Comparing sequences is still a major task in this discovering process, but tends to be more and more time-consuming. KLAST is a sequence comparison software optimized to compare two nucleotides or proteins data sets, typically a set of query sequences and a reference bank. Performances of KLAST are obtained by a new indexing scheme, an optimized seed-extend methodology, and a multi-level parallelism implementation. To scale up to NGS data processing, a Hadoop version has been designed. Experiments demonstrate a good scalability and a large speed-up over BLAST, the reference software of the domain. In addition, computation can be optionally performed on compressed data without any loss in performances

    Extreme ultraviolet laser excitation of isotopic molecular nitrogen: the dipole-allowed spectrum of Âč⁔N₂ and Âč⁎NÂč⁔N

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    Extreme ultraviolet+ultraviolet (XUV+UV) two-photonionizationspectra of the b ÂčΠu(v=0–9), c₃ÂčΠu(v=0,1), o ÂčΠu(v=0,1), câ€Č₄ÂčÎŁâșu(v=1) and bâ€ČÂčÎŁâșu(v=1,3–6) states of Âč⁔N₂ were recorded with a resolution of 0.3 cm⁻Âč full-width at half-maximum (FWHM). In addition, the b ÂčΠu(v=1,5–7) states of Âč⁎NÂč⁔N were investigated with the same laser source. Furthermore, using an ultranarrow bandwidth XUV laser [∌250 MHz (∌0.01 cm⁻Âč) FWHM], XUV+UV ionizationspectra of the b ÂčΠu(v=0–1,5–7), c₃ÂčΠu(v=0), o ÂčΠu(v=0), câ€Č₄ÂčÎŁâșu(v=0), and bâ€ČÂčÎŁâșu(v=1) states of Âč⁔N₂ were recorded in order to better resolve the band-head regions. For Âč⁎NÂč⁔N, ultrahigh resolution spectra of the bÂčΠu(v=0–1,5–6), c₃ÂčΠu(v=0), and bâ€ČÂčÎŁâșu(v=1) states were recorded. Rotational analyses were performed for each band, revealing perturbations arising from the effects of Rydberg-valence interactions in the ÂčΠu and ÂčÎŁâșu states, and rotational coupling between the ÂčΠu and ÂčÎŁâșumanifolds. Finally, a comprehensive perturbation model, based on the diabatic-potential representation used previously for Âč⁎N₂, and involving diagonalization of the full interaction matrix for all Rydberg and valence states of ÂčÎŁâșu and 1Πu symmetry in the energy window 100 000–110 000 cm⁻Âč, was constructed. Term values for Âč⁔N₂ and Âč⁎NÂč⁔N computed using this model were found to be in good agreement with experiment.The work was supported by the European Community, under the Access to Research Infrastructures initiative of the Improving Human Potential Program, Contract No. HPRI-CT-1999-00064. K.G.H.B. was supported by the Scientific Visits to Europe Program of the Australian Academy of Science

    Reference frames and rigid motions in relativity: Applications

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    The concept of rigid reference frame and of constricted spatial metric, given in the previous work [\emph{Class. Quantum Grav.} {\bf 21}, 3067,(2004)] are here applied to some specific space-times: In particular, the rigid rotating disc with constant angular velocity in Minkowski space-time is analyzed, a new approach to the Ehrenfest paradox is given as well as a new explanation of the Sagnac effect. Finally the anisotropy of the speed of light and its measurable consequences in a reference frame co-moving with the Earth are discussed.Comment: 13 pages, 1 figur

    Is it possible to detect gravitational waves with atom interferometers?

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    We investigate the possibility to use atom interferometers to detect gravitational waves. We discuss the interaction of gravitational waves with an atom interferometer and analyze possible schemes

    Vacuum condensates and `ether-drift' experiments

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    The idea of a `condensed' vacuum state is generally accepted in modern elementary particle physics. We argue that this should motivate a new generation of precise `ether-drift' experiments with present-day technology.Comment: Latex file, 12 pages, no figure

    Quantum Limits in Space-Time Measurements

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    Quantum fluctuations impose fundamental limits on measurement and space-time probing. Although using optimised probe fields can allow to push sensitivity in a position measurement beyond the "standard quantum limit", quantum fluctuations of the probe field still result in limitations which are determined by irreducible dissipation mechanisms. Fluctuation-dissipation relations in vacuum characterise the mechanical effects of radiation pressure vacuum fluctuations, which lead to an ultimate quantum noise for positions. For macroscopic reflectors, the quantum noise on positions is dominated by gravitational vacuum fluctuations, and takes a universal form deduced from quantum fluctuations of space-time curvatures in vacuum. These can be considered as ultimate space-time fluctuations, fixing ultimate quantum limits in space-time measurements.Comment: 11 pages, to appear in Quantum and Semiclassical Optic
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