Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats.

AIM: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL). METHODS: Treatment (placebo or V-PYRRO/NO 0.53 micromol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed. RESULTS: Compared to placebo treatment, V-PYRRO/NO improved splanchnic hemodynamics in BDL rats: portal pressure was significantly reduced by 27% (P<0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P=0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P<0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P=0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both sham-operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the liver. CONCLUSION: Continuous administrations of V-PYRRO/NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo-dynamic effects

On the pressure of collisionless particle fluids. The case of solids settling in disks

Aims. Collections of dust, grains, and planetesimals are often treated as a pressureless fluid. We study the validity of neglecting the pressure of such a fluid by computing it exactly for the case of particles settling in a disk. Methods. We solve a modified collisionless Boltzmann equation for the particles and compute the corresponding moments of the phase space distribution: density, momentum, and pressure. Results. We find that whenever the Stokes number, defined as the ratio of the gas drag timescale to the orbital timescale, is more than 1/2, the particle fluid cannot be considered as pressureless. While we show it only in the simple case of particles settling in a laminar disk, this property is likely to remain true for most flows, including turbulent flows.Comment: Accepted for publication as a research note in Astronomy and Astrophysics. Language edite

Planet gaps in the dust layer of 3D protoplanetary disks. II. Observability with ALMA

[Abridged] Aims: We provide predictions for ALMA observations of planet gaps that account for the specific spatial distribution of dust that results from consistent gas+dust dynamics. Methods: In a previous work, we ran full 3D, two-fluid Smoothed Particle Hydrodynamics (SPH) simulations of a planet embedded in a gas+dust T Tauri disk for different planet masses and grain sizes. In this work, the resulting dust distributions are passed to the Monte Carlo radiative transfer code MCFOST to construct synthetic images in the ALMA wavebands. We then use the ALMA simulator to produce images that include thermal and phase noise for a range of angular resolutions, wavelengths, and integration times, as well as for different inclinations, declinations and distances. We also produce images which assume that gas and dust are well mixed with a gas-to-dust ratio of 100 to compare with previous ALMA predictions, all made under this hypothesis. Results: Our findings clearly demonstrate the importance of correctly incorporating the dust dynamics. We show that the gap carved by a 1 M_J planet orbiting at 40 AU is visible with a much higher contrast than the well-mixed assumption would predict. In the case of a 5 M_J planet, we clearly see a deficit in dust emission in the inner disk, and point out the risk of interpreting the resulting image as that of a transition disk with an inner hole if observed in unfavorable conditions. Planet signatures are fainter in more distant disks but declination or inclination to the line-of-sight have little effect on ALMA's ability to resolve the gaps. Conclusions: ALMA has the potential to see signposts of planets in disks of nearby star-forming regions. We present optimized observing parameters to detect them in the case of 1 and 5 M_J planets on 40 AU orbits.Comment: 15 pages, 21 figures, accepted by Astronomy & Astrophysics, a higher resolution version of the paper is available at http://www-obs.univ-lyon1.fr/labo/perso/jean-francois.gonzalez/Papers/Gaps_ALMA.pd

Gap Formation in the Dust Layer of 3D Protoplanetary Disks

We numerically model the evolution of dust in a protoplanetary disk using a two-phase (gas+dust) Smoothed Particle Hydrodynamics (SPH) code, which is non-self-gravitating and locally isothermal. The code follows the three dimensional distribution of dust in a protoplanetary disk as it interacts with the gas via aerodynamic drag. In this work, we present the evolution of a disk comprising 1% dust by mass in the presence of an embedded planet for two different disk configurations: a small, minimum mass solar nebular (MMSN) disk and a larger, more massive Classical T Tauri star (CTTS) disk. We then vary the grain size and planetary mass to see how they effect the resulting disk structure. We find that gap formation is much more rapid and striking in the dust layer than in the gaseous disk and that a system with a given stellar, disk and planetary mass will have a different appearance depending on the grain size and that such differences will be detectable in the millimetre domain with ALMA. For low mass planets in our MMSN models, a gap can open in the dust disk while not in the gas disk. We also note that dust accumulates at the external edge of the planetary gap and speculate that the presence of a planet in the disk may facilitate the growth of planetesimals in this high density region.Comment: 5 page, 4 figures. Accepted for publication in Astrophysics & Space Scienc

The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo [Formula: see text]-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.This work is part of the SIGMA project with the reference FCT-ANR/NEU-OSD/0258/2012, co-financed by the French public funding agency ANR (Agence Nationale pour laRecherche, APP Blanc International II 2012), the Portuguese FCT (Fundação para aCiência e Tecnologia) and the Portuguese North Regional Operational Program (ON.2—O Novo Norte) under the National Strategic Reference Framework (QREN), through theEuropean Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional DevelopmentFund COMPETE (FCOMP-01-0124-FEDER-037298). D.A.B. and A.N. were funded bygrants from FCT-ANR/NEU-OSD/0258/2012. R.M. was supported by the FCT fellow-ship grant with the reference PDE/BDE/113604/2015 from the PhDiHES program. A.C.was supported by a grant from the foundation NRJ. P.M. was funded by FundaçãoCalouste Gulbenkian (Portugal;‘Better mental health during ageing based on temporalprediction of individual brain ageing trajectories TEMPO’) with Grant Number P-139977. France Life Imaging is acknowledged for its support in funding the NeuroSpinplatform of preclinical MRI scanners. The authors also acknowledge and thank EdwardGanz, MD, for proof reading our work

Gathering in Dynamic Rings

The gathering problem requires a set of mobile agents, arbitrarily positioned at different nodes of a network to group within finite time at the same location, not fixed in advanced. The extensive existing literature on this problem shares the same fundamental assumption: the topological structure does not change during the rendezvous or the gathering; this is true also for those investigations that consider faulty nodes. In other words, they only consider static graphs. In this paper we start the investigation of gathering in dynamic graphs, that is networks where the topology changes continuously and at unpredictable locations. We study the feasibility of gathering mobile agents, identical and without explicit communication capabilities, in a dynamic ring of anonymous nodes; the class of dynamics we consider is the classic 1-interval-connectivity. We focus on the impact that factors such as chirality (i.e., a common sense of orientation) and cross detection (i.e., the ability to detect, when traversing an edge, whether some agent is traversing it in the other direction), have on the solvability of the problem. We provide a complete characterization of the classes of initial configurations from which the gathering problem is solvable in presence and in absence of cross detection and of chirality. The feasibility results of the characterization are all constructive: we provide distributed algorithms that allow the agents to gather. In particular, the protocols for gathering with cross detection are time optimal. We also show that cross detection is a powerful computational element. We prove that, without chirality, knowledge of the ring size is strictly more powerful than knowledge of the number of agents; on the other hand, with chirality, knowledge of n can be substituted by knowledge of k, yielding the same classes of feasible initial configurations

The X-ray Flux Distribution of Sagittarius A* as Seen by Chandra

We present a statistical analysis of the X-ray flux distribution of Sgr A* from the Chandra X-ray Observatory's 3 Ms Sgr A* X-ray Visionary Project (XVP) in 2012. Our analysis indicates that the observed X-ray flux distribution can be decomposed into a steady quiescent component, represented by a Poisson process with rate $Q=(5.24\pm0.08)\times10^{-3}$ cts s$^{-1},$ and a variable component, represented by a power law process ($dN/dF\propto F^{-\xi},$ $\xi=1.92_{-0.02}^{+0.03}$). This slope matches our recently-reported distribution of flare luminosities. The variability may also be described by a log-normal process with a median unabsorbed 2-8 keV flux of $1.8^{+0.9}_{-0.6}\times10^{-14}$ erg s$^{-1}$ cm$^{-2}$ and a shape parameter $\sigma=2.4\pm0.2,$ but the power law provides a superior description of the data. In this decomposition of the flux distribution, all of the intrinsic X-ray variability of Sgr A* (spanning at least three orders of magnitude in flux) can be attributed to flaring activity, likely in the inner accretion flow. We confirm that at the faint end, the variable component contributes ~10% of the apparent quiescent flux, as previously indicated by our statistical analysis of X-ray flares in these Chandra observations. Our flux distribution provides a new and important observational constraint on theoretical models of Sgr A*, and we use simple radiation models to explore the extent to which a statistical comparison of the X-ray and infrared can provide insights into the physics of the X-ray emission mechanism.Comment: 13 pages, 7 figures, accepted for publication in ApJ. Comments welcom

The dynamics of stress: a longitudinal MRI study of rat brain structure and connectome

Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem-limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual's resilience/vulnerability to stressful conditions.This work is part of the Sigma project with the reference FCT-ANR/NEU-OSD/ 0258/2012 co-financed by the French public funding agency ANR (Agence National pour la Recherche, APP Blanc International II 2012), the Portuguese FCT (Fundação para a Ciência e Tecnologia) and by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298). DAB and AN were funded by grants from FCT-ANR/NEU-OSD/0258/2012. RM is supported by the FCT fellowship grant with the reference PDE/BDE/113604/2015 from the PhDiHES program; AC was supported by a grant from the foundation NRJ. PM was funded by Fundação Calouste Gulbenkian (Portugal; ‘Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)’), Grant Number P-139977. We thank Drs Patrício Costa and Pedro Moreira for support on the various statistical analyses.info:eu-repo/semantics/publishedVersio