Inhibition of Nuclear Factor of Activated T-Cells (NFAT) Suppresses Accelerated Atherosclerosis in Diabetic Mice

OBJECTIVE OF THE STUDY: Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis. METHODOLOGY AND PRINCIPAL FINDINGS: Streptozotocin (STZ)-induced diabetes in apolipoprotein E(-/-) mice resulted in 2.2 fold increased aortic atherosclerosis and enhanced pro-inflammatory burden, as evidenced by elevated blood monocytes, endothelial activation- and inflammatory markers in aorta, and pro-inflammatory cytokines in plasma. In vivo treatment with the NFAT blocker A-285222 for 4 weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, having no effect in non-diabetic mice. STZ-treated mice exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. NFAT-dependent transcriptional activity was examined in aorta, spleen, thymus, brain, heart, liver and kidney, but only augmented in the aorta of diabetic mice. A-285222 completely blocked this diabetes-driven NFAT activation, but had no impact on the other organs or on splenocyte proliferation or cytokine secretion, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. Instead, NFAT inhibition effectively reduced IL-6, osteopontin, monocyte chemotactic protein 1, intercellular adhesion molecule 1, CD68 and tissue factor expression in the arterial wall and lowered plasma IL-6 in diabetic mice. CONCLUSIONS: Targeting NFAT signaling may be a novel and attractive approach for the treatment of diabetic macrovascular complications

Detailed Analysis of Nearby Bulgelike Dwarf Stars II. Lithium Abundances

Li abundances are derived for a sample of bulgelike stars with isochronal ages of 10-11 Gyr. These stars have orbits with pericentric distances, Rp, as small as 2-3 kpc and Zmax < 1 kpc. The sample comprises G and K dwarf stars in the metallicity range -0.80<[Fe/H]< +0.40. Few data of Li abundances in old turn-off stars (> 4.5 Gyr) within the present metallicity range are available. M67 (4.7 Gyr) and NGC 188 (6 Gyr) are the oldest studied metal-rich open clusters with late-type stars. Li abundances have also been studied for few samples of old metal-rich field stars. In the present work a high dispersion in Li abundances is found for bulgelike stars for all the metallicity range, comparable with values in M67. The role of metallicity and age on a Li depletion pattern is discussed. The possible connection between Li depletion and oxygen abundance due to atmospheric opacity effects is investigated.Comment: 9 pages, 7 figure

Non-gray rotating stellar models and the evolutionary history of the Orion Nebular Cluster

Rotational evolution in the pre-main sequence (PMS) is described with new sets of PMS evolutionary tracks including rotation, non-gray boundary conditions (BCs) and either low (LCE) or high convection efficiency (HCE). Using observational data and our theoretical predictions, we aim at constraining 1) the differences obtained for the rotational evolution of stars within the ONC by means of these different sets of models; 2) the initial angular momentum of low mass stars, by means of their templates in the ONC. We discuss the reliability of current stellar models for the PMS. While the 2D radiation hydrodynamic simulations predict HCE in PMS, semi-empirical calibrations either seem to require that convection is less efficient in PMS than in the following MS phase or are still contradictory. We derive stellar masses and ages for the ONC by using both LCE and HCE. The resulting mass distribution for the bulk of the ONC population is in the range 0.2$-$0.3 {\msun} for our non-gray models and in the range 0.1$-$0.3{\msun} for models having gray BCs. In agreement with Herbst et al. (2002) we find that a large percentage ($\sim$70%) of low-mass stars (M\simlt 0.5{\msun} for LCE; M\simlt0.35{\msun} for HCE) in the ONC appears to be fast rotators (P$<$4days). Three possibilities are open: 1) $\sim$70% of the ONC low mass stars lose their disk at early evolutionary phases; 2)their locking period is shorter; 3) the period evolution is linked to a different morphology of the magnetic fields of the two groups of stars. We also estimate the range of initial angular momentum consistent with the observed periods. The comparisons made indicate that a second parameter is needed to describe convection in the PMS, possibly related to the structural effect of a dynamo magnetic field.Comment: 17 pages, 11 figure

Skyrmions in Magnetic Multilayers: Chirality, Electrical Detection and Current-induced Motion

Sub-100-nm skyrmions are stabilized in magnetic metallic multilayers and observed using transmission electron microscopy, magnetic force microscopy, scanning transmission X-ray microscopy and X-ray resonant magnetic scattering. All these advanced imaging techniques demonstrate the presence of 'pure' Neel skyrmion textures with a determined chirality. Combining these observations with electrical measurements allows us to demonstrate reproducible skyrmion nucleation using current pulses, and measure their contribution to the transverse resistivity to detect them electrically. Once nucleated, skyrmions can be moved using charge currents. We find predominantly a creep-like regime, characterized by disordered skyrmion motion, as observed by atomic force microscopy and scanning transmission X-ray microscopy. These observations are explained qualitatively and to some extent quantitatively by the presence of crystalline grains of about 20nm lateral size with a distribution of magnetic properties

Gravitational collapse and naked singularities

Gravitational collapse is one of the most striking phenomena in gravitational physics. The cosmic censorship conjecture has provided strong motivation for researches in this field. In the absence of general proof for the censorship, many examples have been proposed, in which naked singularity is the outcome of gravitational collapse. Recent development has revealed that there are examples of naked singularity formation in the collapse of physically reasonable matter fields, although the stability of these examples is still uncertain. We propose the concept of ``effective naked singularities'', which will be quite helpful because general relativity has the limitation of its application for high-energy end. The appearance of naked singularities is not detestable but can open a window for new physics of strongly curved spacetimes.Comment: 12 pages, to appear in the Proceedings of the International Conference on Gravitation and Cosmology (ICGC-2004), ed. by B.R. Iyer, V. Kuriakose and C.V. Vishveshwara, published by Pramana, minor correction

Control of magnetic anisotropy by orbital hybridization in (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattice

The asymmetry of chemical nature at the hetero-structural interface offers an unique opportunity to design desirable electronic structure by controlling charge transfer and orbital hybridization across the interface. However, the control of hetero-interface remains a daunting task. Here, we report the modulation of interfacial coupling of (La0.67Sr0.33MnO3)n/(SrTiO3)n superlattices by manipulating the periodic thickness with n unit cells of SrTiO3 and n unit cells La0.67Sr0.33MnO3. The easy axis of magnetic anisotropy rotates from in-plane (n = 10) to out-of-plane (n = 2) orientation at 150 K. Transmission electron microscopy reveals enlarged tetragonal ratio > 1 with breaking of volume conservation around the (La0.67Sr0.33MnO3)n/(SrTiO3)n interface, and electronic charge transfer from Mn to Ti 3d orbitals across the interface. Orbital hybridization accompanying the charge transfer results in preferred occupancy of 3d3z2-r2 orbital at the interface, which induces a stronger electronic hopping integral along the out-of-plane direction and corresponding out-of-plane magnetic easy axis for n = 2. We demonstrate that interfacial orbital hybridization in superlattices of strongly correlated oxides may be a promising approach to tailor electronic and magnetic properties in device applications

Measurement of the Ge 70 (n,γ) cross section up to 300 keV at the CERN n-TOF facility

©2019 American Physical Society.Neutron capture data on intermediate mass nuclei are of key importance to nucleosynthesis in the weak component of the slow neutron capture processes, which occurs in massive stars. The (n,γ) cross section on Ge70, which is mainly produced in the s process, was measured at the neutron time-of-flight facility n-TOF at CERN. Resonance capture kernels were determined up to 40 keV neutron energy and average cross sections up to 300 keV. Stellar cross sections were calculated from kT=5 keV to kT=100 keV and are in very good agreement with a previous measurement by Walter and Beer (1985) and recent evaluations. Average cross sections are in agreement with Walter and Beer (1985) over most of the neutron energy range covered, while they are systematically smaller for neutron energies above 150 keV. We have calculated isotopic abundances produced in s-process environments in a 25 solar mass star for two initial metallicities (below solar and close to solar). While the low metallicity model reproduces best the solar system germanium isotopic abundances, the close to solar model shows a good global match to solar system abundances in the range of mass numbers A=60-80.Peer reviewedFinal Published versio

Towards the high-accuracy determination of the 238U fission cross section at the threshold region at CERN - N-TOF

The 238U fission cross section is an international standard beyond 2 MeV where the fission plateau starts. However, due to its importance in fission reactors, this cross-section should be very accurately known also in the threshold region below 2 MeV. The 238U fission cross section has been measured relative to the 235U fission cross section at CERN - n-TOF with different detection systems. These datasets have been collected and suitably combined to increase the counting statistics in the threshold region from about 300 keV up to 3 MeV. The results are compared with other experimental data, evaluated libraries, and the IAEA standards