222 research outputs found

    Experimenting an optical second with strontium lattice clocks

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    Progress in realizing the SI second had multiple technological impacts and enabled to further constraint theoretical models in fundamental physics. Caesium microwave fountains, realizing best the second according to its current definition with a relative uncertainty of 2-4x10^(-16), have already been superseded by atomic clocks referenced to an optical transition, both more stable and more accurate. Are we ready for a new definition of the second? Here we present an important step in this direction: our system of five clocks connects with an unprecedented consistency the optical and the microwave worlds. For the first time, two state-of-the-art strontium optical lattice clocks are proven to agree within their accuracy budget, with a total uncertainty of 1.6x10^(-16). Their comparison with three independent caesium fountains shows a degree of reproducibility henceforth solely limited at the level of 3.1x10^(-16) by the best realizations of the microwave-defined second.Comment: 9 pages, 4 figures, 2 table

    Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade

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    <p>Abstract</p> <p>Background</p> <p>Reactive oxygen species (ROS), superoxide and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), are necessary for appropriate responses to immune challenges. In the brain, excess superoxide production predicts neuronal cell loss, suggesting that Parkinson's disease (PD) with its wholesale death of dopaminergic neurons in substantia nigra pars compacta (nigra) may be a case in point. Although microglial NADPH oxidase-produced superoxide contributes to dopaminergic neuron death in an MPTP mouse model of PD, this is secondary to an initial die off of such neurons, suggesting that the initial MPTP-induced death of neurons may be via activation of NADPH oxidase in neurons themselves, thus providing an early therapeutic target.</p> <p>Methods</p> <p>NADPH oxidase subunits were visualized in adult mouse nigra neurons and in N27 rat dopaminergic cells by immunofluorescence. NADPH oxidase subunits in N27 cell cultures were detected by immunoblots and RT-PCR. Superoxide was measured by flow cytometric detection of H<sub>2</sub>O<sub>2</sub>-induced carboxy-H<sub>2</sub>-DCFDA fluorescence. Cells were treated with MPP+ (MPTP metabolite) following siRNA silencing of the Nox2-stabilizing subunit p22<sup>phox</sup>, or simultaneously with NADPH oxidase pharmacological inhibitors or with losartan to antagonize angiotensin II type 1 receptor-induced NADPH oxidase activation.</p> <p>Results</p> <p>Nigral dopaminergic neurons <it>in situ</it> expressed three subunits necessary for NADPH oxidase activation, and these as well as several other NADPH oxidase subunits and their encoding mRNAs were detected in unstimulated N27 cells. Overnight MPP+ treatment of N27 cells induced Nox2 protein and superoxide generation, which was counteracted by NADPH oxidase inhibitors, by siRNA silencing of p22<sup>phox</sup>, or losartan. A two-wave ROS cascade was identified: 1) as a first wave, mitochondrial H<sub>2</sub>O<sub>2 </sub>production was first noted at three hours of MPP+ treatment; and 2) as a second wave, H<sub>2</sub>O<sub>2 </sub>levels were further increased by 24 hours. This second wave was eliminated by pharmacological inhibitors and a blocker of protein synthesis.</p> <p>Conclusions</p> <p>A two-wave cascade of ROS production is active in nigral dopaminergic neurons in response to neurotoxicity-induced superoxide. Our findings allow us to conclude that superoxide generated by NADPH oxidase present in nigral neurons contributes to the loss of such neurons in PD. Losartan suppression of nigral-cell superoxide production suggests that angiotensin receptor blockers have potential as PD preventatives.</p

    On the potential application of DFT methods in predicting the interaction-induced electric properties of molecular complexes. Molecular H-bonded chains as a case of study

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    A detailed analysis of the selected DFT functionals for the calculations of interaction-induced dipole moment, polarizability and first-order hyperpolarizability has been carried out. The hydrogen-bonded model chains consisting of HF, H2CO and H3N molecules have been chosen as a case study. The calculations of the components of the static electric properties using the diffuse Dunning’s basis set (aug-cc-pVDZ) have been performed employing different types of density functionals (B3LYP, LC-BLYP, PBE0, M06-2X and CAM-B3LYP). Obtained results have been compared with those gained at the CCSD(T) level of theory. The counterpoise correction scheme, namely site-site function counterpoise, has been applied in order to eliminate basis set superposition error. The performed tests allow to conclude that the DFT functionals can provide a useful tool for prediction of the interaction-induced electric properties, however a caution has to be urged to their decomposition to the two- and many-body terms

    High-resolution MCP-TimePix3 imaging/timing detector for antimatter physics

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    We present a hybrid imaging/timing detector for force sensitive inertial measurements designed for measurements on positronium, the metastable bound state of an electron and a positron, but also suitable for applications involving other low intensity, low energy beams of neutral (antimatter)-atoms, such as antihydrogen. The performance of the prototype detector was evaluated with a tunable low energy positron beam, resulting in a spatial resolution of approximate t

    Observation of Coherent Elastic Neutrino-Nucleus Scattering

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    The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

    Positronium laser cooling via the 13S1^3S-23P2^3P transition with a broadband laser pulse

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    We report on laser cooling of a large fraction of positronium (Ps) in free-flight by strongly saturating the 13S1^3S-23P2^3P transition with a broadband, long-pulsed 243 nm alexandrite laser. The ground state Ps cloud is produced in a magnetic and electric field-free environment. We observe two different laser-induced effects. The first effect is an increase in the number of atoms in the ground state after the time Ps has spent in the long-lived 33P3^3P states. The second effect is the one-dimensional Doppler cooling of Ps, reducing the cloud's temperature from 380(20) K to 170(20) K. We demonstrate a 58(9) % increase in the coldest fraction of the Ps ensemble.Comment: 6 pages, 5 figure

    Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability.

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    Monocytes play a central role in regulating inflammation in response to infection or injury, and during auto-inflammatory diseases. Human blood contains classical, intermediate and non-classical monocyte subsets that each express characteristic patterns of cell surface CD16 and CD14; each subset also has specific functional properties, but the mechanisms underlying many of their distinctive features are undefined. Of particular interest is how monocyte subsets regulate secretion of the apical pro-inflammatory cytokine IL-1β, which is central to the initiation of immune responses but is also implicated in the pathology of various auto-immune/auto-inflammatory conditions. Here we show that primary human non-classical monocytes, exposed to LPS or LPS + BzATP (3'-O-(4-benzoyl)benzyl-ATP, a P2X7R agonist), produce approx. 80% less IL-1β than intermediate or classical monocytes. Despite their low CD14 expression, LPS-sensing, caspase-1 activation and P2X7R activity were comparable in non-classical monocytes to other subsets: their diminished ability to produce IL-1β instead arose from 50% increased IL-1β mRNA decay rates, mediated by Hsp27. These findings identify the Hsp27 pathway as a novel therapeutic target for the management of conditions featuring dysregulated IL-1β production, and represent an advancement in understanding of both physiological inflammatory responses and the pathogenesis of inflammatory diseases involving monocyte-derived IL-1β
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