1,384 research outputs found
Parametric attosecond pulse amplification far from the ionization threshold from high order harmonic generation in He
Parametric amplification of attosecond coherent pulses around 100 eV at the
single-atom level is demonstrated for the first time by using the 3D
time-dependent Schr{\"o}dinger equation in high-harmonic generation processes
from excited states of He. We present the attosecond dynamics of the
amplification process far from the ionization threshold and resolve the physics
behind it. The amplification of a particular central photon energy requires the
seed XUV pulses to be perfectly synchronized in time with the driving laser
field for stimulated recombination to the He ground state and is only
produced in a few specific laser cycles in agreement with the experimental
measurements. Our simulations show that the amplified photon energy region can
be controlled by varying the peak intensity of the laser field. Our results
pave the way to the realization of compact attosecond pulse intense XUV lasers
with broad applications
Conformationally-Locked C-Glycosides: Tuning Aglycone Interactions for Optimal Cheperone Behaviour in Gaucher Fibroblasts
A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver β-glucosidase/β-galactosidase and specific inhibition of human β-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location. Molecular dynamics simulations highlighted the paramount importance of an optimal orientation of the hydrophobic substituent to warrant efficient non-glycone interactions, which are critical for the binding affinity. The results provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound AmbroxolMinisterio de EconomĂa y Competitividad CTQ2012-36365, SAF2013-44021-RJunta de AndalucĂa FQM-1467European Union Seventh Framework Programme FP7-People-2012-CI
Nodal degenerations of plane curves and Galois covers
Globally irreducible nodes (i.e. nodes whose branches belong to the same
irreducible component) have mild effects on the most common topological
invariants of an algebraic curve. In other words, adding a globally irreducible
node (simple nodal degeneration) to a curve should not change them a lot. In
this paper we study the effect of nodal degeneration of curves on fundamental
groups and show examples where simple nodal degenerations produce
non-isomorphic fundamental groups and this can be detected in an algebraic way
by means of Galois coverings.Comment: 16 pages, 3 figure
The Winding Road to Relapse: Forging a New Understanding of Cue-Induced Reinstatement Models and Their Associated Neural Mechanisms
In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will discuss how models of drug addiction and relapse should more systematically evaluate these different types of stimuli to better understand the neurobiology underlying craving and relapse. In this way, behavioral and pharmacotherapeutic interventions may be better tailored to promote drug use cessation outcomes and long-term abstinence
Efficient construction of the hexacyclic ring core of palau'amine : the pKa concept for proceeding with unfavorable equilibrium reactions
Palau'amine has received a great deal of attention as an attractive synthetic target due to its intriguing molecular architecture and significant immunosuppressive activity, and we achieved its total synthesis in 2015. However, the synthesized palau'amine has not been readily applicable to the mechanistic study of immunosuppressive activity, because it requires 45 longest linear steps from a commercially available compound. Here, we report the short-step construction of the ABCDEF hexacyclic ring core of palau'amine. The construction of the CDE tricyclic ring core in a single step is achieved by our pKa concept for proceeding with unfavorable equilibrium reactions, and a palau'amine analog without the aminomethyl and chloride groups is synthesized in 20 longest linear steps from the same starting material. The palau'amine analog is confirmed to retain the immunosuppressive activity. The present synthetic approach for a palau'amine analog has the potential for use in the development of palau'amine probes for mechanistic elucidation
O adsorption and incipient oxidation of the Mg(0001) surface
First principles density functional calculations are used to study the early
oxidation stages of the Mg(0001) surface for oxygen coverages 1/16 <= Theta <=
3 monolayers. It is found that at very low coverages O is incorporated below
the topmost Mg layer in tetrahedral sites. At higher oxygen-load the binding in
on-surface sites is increased but at one monolayer coverage the on-surface
binding is still about 60 meV weaker than for subsurface sites. The subsurface
octahedral sites are found to be unfavorable compared to subsurface tetrahedral
sites and to on-surface sites. At higher coverages oxygen adsorbs both under
the surface and up. Our calculations predict island formation and clustering of
incorporated and adsorbed oxygen in agreement with previous calculations. The
calculated configurations are compared with the angle-scanned x-ray
photoelectron diffraction experiment to determine the geometrical structure of
the oxidized Mg(0001) surface.Comment: 10 pages, 5 figure
Study on History of International Exchange and International Conference on Plasma Physics and Nuclear Fusion Research
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