154 research outputs found

    Momentum isotropisation in random potentials

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    When particles are multiply scattered by a random potential, their momentum distribution becomes isotropic on average. We study this quantum dynamics numerically and with a master equation. We show how to measure the elastic scattering time as well as characteristic isotropisation times, which permit to reconstruct the scattering phase function, even in rather strong disorder.Comment: 5 pages, paper contributed to Lyon BEC 2012; v2 minor changes, version published in prin

    Why are we failing to implement imaging studies with radiolabelled new molecular entities in early oncology drug development?

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    In early drug development advanced imaging techniques can help with progressing new molecular entities (NME) to subsequent phases of drug development and thus reduce attrition. However, several organizational, operational, and regulatory hurdles pose a significant barrier, potentially limiting the impact these techniques can have on modern drug development. Positron emission tomography (PET) of radiolabelled NME is arguably the best example of a complex technique with a potential to deliver unique decision-making data in small cohorts of subjects. However, to realise this potential the impediments to timely inclusion of PET into the drug development process must be overcome. In the present paper, we discuss the value of PET imaging with radiolabelled NME during early anticancer drug development, as exemplified with one such NME. We outline the multiple hurdles and propose options on how to streamline the organizational steps for future studies

    Synthesis of carbon-11 radiolabelled transition metal complexes using 11C-dithiocarbamates

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    A novel radiolabelling method exploiting 11C-dithiocarbamate ligands has been used to generate 11C-labelled Au(I), Au(III), Pd(II) and Pt(II) complexes in high radiochemical yields (71–99%). Labelled complexes were prepared in a rapid one-pot procedure via the substitution reaction of 11C-dithiocarbamate ligands with appropriate transition metal chloride precursors

    Theoretical Analysis of a Large Momentum Beamsplitter using Bloch Oscillations

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    In this paper, we present the implementation of Bloch oscillations in an atomic interferometer to increase the separation of the two interfering paths. A numerical model, in very good agreement with the experiment, is developed. The contrast of the interferometer and its sensitivity to phase fluctuations and to intensity fluctuations are also calculated. We demonstrate that the sensitivity to phase fluctuations can be significantly reduced by using a suitable arrangement of Bloch oscillations pulses

    Transport regimes of cold gases in a two-dimensional anisotropic disorder

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    We numerically study the dynamics of cold atoms in a two-dimensional disordered potential. We consider an anisotropic speckle potential and focus on the classical regime, which is relevant to some recent experiments. First, we study the behavior of particles with a fixed energy and identify different transport regimes. For low energy, the particles are classically localized due to the absence of a percolating cluster. For high energy, the particles undergo normal diffusion and we show that the diffusion constants scale algebraically with the particle energy, with an anisotropy factor which significantly differs from that of the disordered potential. For intermediate energy, we find a transient sub-diffusive regime, which is relevant to the time scale of typical experiments. Second, we study the behavior of a cold-atomic gas with an arbitrary energy distribution, using the above results as a groundwork. We show that the density profile of the atomic cloud in the diffusion regime is strongly peaked and, in particular, that it is not Gaussian. Its behavior at large distances allows us to extract the energy-dependent diffusion constants from experimental density distributions. For a thermal cloud released into the disordered potential, we show that our numerical predictions are in agreement with experimental findings. Not only does this work give insights to recent experimental results, but it may also serve interpretation of future experiments searching for deviation from classical diffusion and traces of Anderson localization.Comment: 19 pages, 16 figure

    Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile: A retrospective observational study

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    BACKGROUND: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in plasma ammonia is required to prevent neurological complications. This retrospective, multicentre, open-label, uncontrolled, phase IIIb study evaluated the efficacy and safety of carglumic acid, a synthetic structural analogue of NAG, for treating hyperammonaemia during OA decompensation. METHODS: Eligible patients had confirmed OA and hyperammonaemia (plasma NH3 > 60 μmol/L) in ≥1 decompensation episode treated with carglumic acid (dose discretionary, mean (SD) first dose 96.3 (73.8) mg/kg). The primary outcome was change in plasma ammonia from baseline to endpoint (last available ammonia measurement at ≤18 hours after the last carglumic acid administration, or on Day 15) for each episode. Secondary outcomes included clinical response and safety. RESULTS: The efficacy population (received ≥1 dose of study drug and had post-baseline measurements) comprised 41 patients (MMA: 21, PA: 16, IVA: 4) with 48 decompensation episodes (MMA: 25, PA: 19, IVA: 4). Mean baseline plasma ammonia concentration was 468.3 (±365.3) μmol/L in neonates (29 episodes) and 171.3 (±75.7) μmol/L in non-neonates (19 episodes). At endpoint the mean plasma NH3 concentration was 60.7 (±36.5) μmol/L in neonates and 55.2 (±21.8) μmol/L in non-neonates. Median time to normalise ammonaemia was 38.4 hours in neonates vs 28.3 hours in non-neonates and was similar between OA subgroups (MMA: 37.5 hours, PA: 36.0 hours, IVA: 40.5 hours). Median time to ammonia normalisation was 1.5 and 1.6 days in patients receiving and not receiving concomitant scavenger therapy, respectively. Although patients receiving carglumic acid with scavengers had a greater reduction in plasma ammonia, the endpoint ammonia levels were similar with or without scavenger therapy. Clinical symptoms improved with therapy. Twenty-five of 57 patients in the safety population (67 episodes) experienced AEs, most of which were not drug-related. Overall, carglumic acid seems to have a good safety profile for treating hyperammonaemia during OA decompensation. CONCLUSION: Carglumic acid when used with or without ammonia scavengers, is an effective treatment for restoration of normal plasma ammonia concentrations in hyperammonaemic episodes in OA patients

    Molecular evolution of viral multifunctional proteins: the case of Potyvirus HC-Pro

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    [EN] Our knowledge on the mode of evolution of the multifunctional viral proteins remains incomplete. To tackle this problem, here, we have investigated the evolutionary dynamics of the potyvirus multifunctional protein HC-Pro, with particular focus on its functional domains. The protein was partitioned into the three previously described functional domains, and each domain was analyzed separately and assembled. We searched for signatures of adaptive evolution and evolutionary dependencies of amino acid sites within and between the three domains using the entire set of available potyvirus sequences in GenBank. Interestingly, we identified strongly significant patterns of co-occurrence of adaptive events along the phylogenetic tree in the three domains. These patterns suggest that Domain I, whose main function is to mediate aphid transmission, has likely been coevolving with the other two domains, which are involved in different functions but all requiring the capacity to bind RNA. By contrast, episodes of positive selection on Domains II and III did not correlate, reflecting a trade-off between their evolvability and their evolutionary dependency likely resulting from their functional overlap. Covariation analyses have identified several groups of amino acids with evidence of concerted variation within each domain, but interdomain significant covariations were only found for Domains II and III, further reflecting their functional overlappingThis work was supported by grants BFU2012-30805 (SFE) and BFU2012-36346 (MAF) from the Spanish Direccio´n General de Investigacio´n Cientı´fica y Te´cnica and by an EMBO Short-Term Fellowship and the Mentoring Program from the Foundation for Polish Science (BHJ).Hasiów-Jaroszewska, B.; Fares Riaño, MA.; Elena Fito, SF. (2014). Molecular evolution of viral multifunctional proteins: the case of Potyvirus HC-Pro. 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