573 research outputs found
Hydrogen Spectroscopy with a Lamb-shift Polarimeter - An Alternative Approach Towards Anti-Hydrogen Spectroscopy Experiments
A Lamb-shift polarimeter, which has been built for a fast determination of
the polarization of protons and deuterons of an atomic-beam source and which is
frequently used in the ANKE experiment at COSY-J\"ulich, is shown to be an
excellent device for atomic-spectroscopy measurements of metastable hydrogen
isotopes. It is demonstrated that magnetic and electric dipole transitions in
hydrogen can be measured as a function of the external magnetic field, giving
access to the full Breit-Rabi diagram for the and the
states. This will allow the study of hyperfine structure, factors and the
classical Lamb shift. Although the data are not yet competitive with
state-of-the-art measurements, the potential of the method is enormous,
including a possible application to anti-hydrogen spectroscopy.Comment: 6 pages, 7 figures, accepted by European Physical Journal
Monte Carlo Methods for Rough Free Energy Landscapes: Population Annealing and Parallel Tempering
Parallel tempering and population annealing are both effective methods for
simulating equilibrium systems with rough free energy landscapes. Parallel
tempering, also known as replica exchange Monte Carlo, is a Markov chain Monte
Carlo method while population annealing is a sequential Monte Carlo method.
Both methods overcome the exponential slowing associated with high free energy
barriers. The convergence properties and efficiency of the two methods are
compared. For large systems, population annealing initially converges to
equilibrium more rapidly than parallel tempering for the same amount of
computational work. However, parallel tempering converges exponentially and
population annealing inversely in the computational work so that ultimately
parallel tempering approaches equilibrium more rapidly than population
annealing.Comment: 10 pages, 3 figure
Nuclear spins, magnetic moments and quadrupole moments of Cu isotopes from N = 28 to N = 46: probes for core polarization effects
Measurements of the ground-state nuclear spins, magnetic and quadrupole
moments of the copper isotopes from 61Cu up to 75Cu are reported. The
experiments were performed at the ISOLDE facility, using the technique of
collinear laser spectroscopy. The trend in the magnetic moments between the
N=28 and N=50 shell closures is reasonably reproduced by large-scale
shell-model calculations starting from a 56Ni core. The quadrupole moments
reveal a strong polarization of the underlying Ni core when the neutron shell
is opened, which is however strongly reduced at N=40 due to the parity change
between the and orbits. No enhanced core polarization is seen beyond
N=40. Deviations between measured and calculated moments are attributed to the
softness of the 56Ni core and weakening of the Z=28 and N=28 shell gaps.Comment: 13 pagers, 19 figures, accepted by Physical Review
Metabolic adaptation to the chronic loss of Ca 2+ signaling induced by KO of IP 3 receptors or the mitochondrial Ca 2+ uniporter
Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the chronic loss of cytosolic and/or mitochondrial Ca2+ signaling. Our results show that TKO cells (exhibiting total loss of Ca2+ signaling) are viable, displaying a lower proliferation and oxygen consumption rate, with no significant changes in ATP levels, even when made to rely solely on the TCA cycle for energy production. MCU KO cells also maintained normal ATP levels but showed increased proliferation, oxygen consumption, and metabolism of both glucose and glutamine. However, MCU KO cells were unable to maintain ATP levels and died when relying solely on the TCA cycle for energy. We conclude that constitutive Ca2+ signaling is dispensable for the bioenergetic needs of both IP3R TKO and MCU KO human cancer cells, likely because of adequate basal glycolytic and TCA cycle flux. However, in MCU KO cells, the higher energy expenditure associated with increased proliferation and oxygen consumption makes these cells more prone to bioenergetic failure under conditions of metabolic stress
Forward K+ production in subthreshold pA collisions at 1.0 GeV
K+ meson production in pA (A = C, Cu, Au) collisions has been studied using
the ANKE spectrometer at an internal target position of the COSY-Juelich
accelerator. The complete momentum spectrum of kaons emitted at forward angles,
theta < 12 degrees, has been measured for a beam energy of T(p)=1.0 GeV, far
below the free NN threshold of 1.58 GeV. The spectrum does not follow a thermal
distribution at low kaon momenta and the larger momenta reflect a high degree
of collectivity in the target nucleus.Comment: 4 pages, 3 figure
Determination of Noncovalent Binding Using a Continuous Stirred Tank Reactor as a Flow Injection Device Coupled to Electrospray Ionization Mass Spectrometry
Antimony(III)-D, L-tartrates exhibit proton-assisted enantioselective binding in solution and in the gas phase
Hydroxychloroquine in rheumatic autoimmune disorders and beyond
Initially used as antimalarial drugs, hydroxychloroquine (HCQ) and, to a lesser extent, chloroquine (CQ) are currently being used to treat several diseases. Due to its cost-effectiveness, safety and efficacy, HCQ is especially used in rheumatic autoimmune disorders (RADs), such as systemic lupus erythematosus, primary Sjögren's syndrome and rheumatoid arthritis. Despite this widespread use in the clinic, HCQ molecular modes of action are still not completely understood. By influencing several cellular pathways through different mechanisms, CQ and HCQ inhibit multiple endolysosomal functions, including autophagy, as well as endosomal Toll-like receptor activation and calcium signalling. These effects alter several aspects of the immune system with the synergistic consequence of reducing pro-inflammatory cytokine production and release, one of the most marked symptoms of RADs. Here, we review the current knowledge on the molecular modes of action of these drugs and the circumstances under which they trigger side effects. This is of particular importance as the therapeutic use of HCQ is expanding beyond the treatment of malaria and RADs
Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid
Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria
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