18F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis.

Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2'-deoxy-2'-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures deoxyribonucleoside salvage and accumulates preferentially in immune cells. We hypothesized that 18F-FAC PET could noninvasively image brain-infiltrating leukocytes. Methods: Healthy mice were imaged with 18F-FAC PET to quantify if this radiotracer crosses the blood-brain barrier (BBB). Experimental autoimmune encephalomyelitis (EAE) is a mouse disease model with brain-infiltrating leukocytes. To determine whether 18F-FAC accumulates in brain-infiltrating leukocytes, EAE mice were analyzed with 18F-FAC PET, digital autoradiography, and immunohistochemistry, and deoxyribonucleoside salvage activity in brain-infiltrating leukocytes was analyzed ex vivo. Fingolimod-treated EAE mice were imaged with 18F-FAC PET to assess if this approach can monitor the effect of an immunomodulatory drug on brain-infiltrating leukocytes. PET scans of individuals injected with 2-chloro-2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosyl-adenine (18F-CFA), a PET radiotracer that measures deoxyribonucleoside salvage in humans, were analyzed to evaluate whether 18F-CFA crosses the human BBB. Results: 18F-FAC accumulates in the healthy mouse brain at levels similar to 18F-FAC in the blood (2.54 ± 0.2 and 3.04 ± 0.3 percentage injected dose per gram, respectively) indicating that 18F-FAC crosses the BBB. EAE mice accumulate 18F-FAC in the brain at 180% of the levels of control mice. Brain 18F-FAC accumulation localizes to periventricular regions with significant leukocyte infiltration, and deoxyribonucleoside salvage activity is present at similar levels in brain-infiltrating T and innate immune cells. These data suggest that 18F-FAC accumulates in brain-infiltrating leukocytes in this model. Fingolimod-treated EAE mice accumulate 18F-FAC in the brain at 37% lower levels than control-treated EAE mice, demonstrating that 18F-FAC PET can monitor therapeutic interventions in this mouse model. 18F-CFA accumulates in the human brain at 15% of blood levels (0.08 ± 0.01 and 0.54 ± 0.07 SUV, respectively), indicating that 18F-CFA does not cross the BBB in humans. Conclusion: 18F-FAC PET can visualize brain-infiltrating leukocytes in a mouse MS model and can monitor the response of these cells to an immunomodulatory drug. Translating this strategy into humans will require exploring additional radiotracers

Mechanism for flux guidance by micrometric antidot arrays in superconducting films

A study of magnetic flux penetration in a superconducting film patterned with arrays of micron sized antidots (microholes) is reported. Magneto-optical imaging (MOI) of a YBCO film shaped as a long strip with perpendicular antidot arrays revealed both strong guidance of flux, and at the same time large perturbations of the overall flux penetration and flow of current. These results are compared with a numerical flux creep simulation of a thin superconductor with the same antidot pattern. To perform calculations on such a complex geometry, an efficient numerical scheme for handling the boundary conditions of the antidots and the nonlocal electrodynamics was developed. The simulations reproduce essentially all features of the MOI results. In addition, the numerical results give insight into all other key quantities, e.g., the electrical field, which becomes extremely large in the narrow channels connecting the antidots.Comment: 8 pages, 7 figure

Generalized information entropies depending only on the probability distribution

Systems with a long-term stationary state that possess as a spatio-temporally fluctuation quantity $\beta$ can be described by a superposition of several statistics, a "super statistics". We consider first, the Gamma, log-normal and $F$-distributions of $\beta$. It is assumed that they depend only on $p_l$, the probability associated with the microscopic configuration of the system. For each of the three $\beta-$distributions we calculate the Boltzmann factors and show that they coincide for small variance of the fluctuations. For the Gamma distribution it is possible to calculate the entropy in a closed form, depending on $p_l$, and to obtain then an equation relating $p_l$ with $\beta E_l$. We also propose, as other examples, new entropies close related with the Kaniadakis and two possible Sharma-Mittal entropies. The entropies presented in this work do not depend on a constant parameter $q$ but on $p_l$. For the $p_l$-Gamma distribution and its corresponding $B_{p_l}(E)$ Boltzmann factor and the associated entropy, we show the validity of the saddle-point approximation. We also briefly discuss the generalization of one of the four Khinchin axioms to get this proposed entropy.Comment: 13 pages, 3 figure

P27 Repair of experimental articular cartilage lesions with autologous chondrocytes onto biodegradable scaffolds by arthroscopy in horses

n/

The Orbit of the New Milky Way Globular Cluster FSR1716 =VVV-GC05

Indexación: Scopus.We use deep, multi-epoch near-IR images of the VISTA Variables in the Via Lictea (VVV) Survey to measure proper motions (PMs) of stars in the Milky Way globular cluster (GC) FSR1716 = VVV-GC05. The colormagnitude diagram of this object, made by using PM-selected members, shows an extended horizontal branch, nine confirmed RR Lyrae (RRL) members in the instability strip, and possibly several hotter stars extending to the blue. Based on the fundamental-mode (ab-type) RRL stars that move coherently with the cluster, we confirmed that FSR1716 is an Oosterhoff I GC with a mean period aPabn = 0.574 days. Intriguingly, we detect tidal extensions to both sides of this cluster in the spatial distribution of PM-selected member stars. Also, one of the confirmed RRabs is located -11 arcmin in projection from the cluster center, suggesting that FSR1716 may be losing stars due to the gravitational interaction with the Galaxy. We also measure radial velocities (RVs) for five cluster red giants selected using the PMs. The combination of RVs and PMs allow us to compute for the first time the orbit of this GC, using an updated Galactic potential. The orbit results to be confined within|Zmax| < 2.0 kpc, and has eccentricity 0.4 < e < 0.6, with perigalactic distance 1.5 < Rperi (kpc) < 2.3, and apogalactic distance 5.3 < Rapo (kpc) < 6.4. We conclude that, in agreement with its relatively low metallicity ([Fe/H] =-1.4 dex), this is an inner-halo GC plunging into the disk of the Galaxy. As such, this is a unique object with which to test the dynamical processes that contribute to the disruption of Galactic GCs. © 2018. The American Astronomical Society. All rights reserved.https://iopscience.iop.org/article/10.3847/1538-4357/aacd0

Lattice effects and current reversal in superconducting ratchets

Competition between the vortex lattice and a lattice of asymmetric artificial defects is shown to play a crucial role in ratchet experiments in superconducting films. We present a novel and collective mechanism for current reversal based on a reconfiguration of the vortex lattice. In contrast to previous models of vortex current reversal, the mechanism is based on the global response of the vortex lattice to external forces.Comment: 12 pages, 7 figure