270 research outputs found

    Methane storms as a driver of Titan's dune orientation

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    Titan's equatorial regions are covered by eastward propagating linear dunes. This direction is opposite to mean surface winds simulated by Global Climate Models (GCMs), which are oriented westward at these latitudes, similar to trade winds on Earth. Different hypotheses have been proposed to address this apparent contradiction, involving Saturn's gravitational tides, large scale topography or wind statistics, but none of them can explain a global eastward dune propagation in the equatorial band. Here we analyse the impact of equinoctial tropical methane storms developing in the superrotating atmosphere (i.e. the eastward winds at high altitude) on Titan's dune orientation. Using mesoscale simulations of convective methane clouds with a GCM wind profile featuring superrotation, we show that Titan's storms should produce fast eastward gust fronts above the surface. Such gusts dominate the aeolian transport, allowing dunes to extend eastward. This analysis therefore suggests a coupling between superrotation, tropical methane storms and dune formation on Titan. Furthermore, together with GCM predictions and analogies to some terrestrial dune fields, this work provides a general framework explaining several major features of Titan's dunes: linear shape, eastward propagation and poleward divergence, and implies an equatorial origin of Titan's dune sand.Comment: Published online on Nature Geoscience on 13 April 201

    Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase

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    BACKGROUND: Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated. METHODS: Wistar rats were used (6 in each group) – Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion. RESULTS: Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase. CONCLUSIONS: These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion

    Twice-daily amprenavir 1200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-1-infected patients

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    BACKGROUND: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). METHODS: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. RESULTS: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log(10 )copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1–4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. CONCLUSIONS: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable

    Methane drizzle on Titan

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    Saturn's moon Titan shows landscapes with fluvial features(1) suggestive of hydrology based on liquid methane. Recent efforts in understanding Titan's methane hydrological cycle have focused on occasional cloud outbursts near the south pole(2-4) or cloud streaks at southern mid-latitudes(5,6) and the mechanisms of their formation. It is not known, however, if the clouds produce rain or if there are also non-convective clouds, as predicted by several models(7-11). Here we show that the in situ data on the methane concentration and temperature profile in Titan's troposphere point to the presence of layered optically thin stratiform clouds. The data indicate an upper methane ice cloud and a lower, barely visible, liquid methane-nitrogen cloud, with a gap in between. The lower, liquid, cloud produces drizzle that reaches the surface. These non-convective methane clouds are quasi-permanent features supported by the global atmospheric circulation, indicating that methane precipitation occurs wherever there is slow upward motion. This drizzle is a persistent component of Titan's methane hydrological cycle and, by wetting the surface on a global scale, plays an active role in the surface geology of Titan.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62668/1/nature04948.pd

    Exact Hybrid Particle/Population Simulation of Rule-Based Models of Biochemical Systems

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    Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity, an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications. Rule-based modeling overcomes this problem by representing molecules as structured objects and encoding their interactions as pattern-based rules. This greatly simplifies the process of model specification, avoiding the tedious and error prone task of manually enumerating all species and reactions that can potentially exist in a system. From a simulation perspective, rule-based models can be expanded algorithmically into fully-enumerated reaction networks and simulated using a variety of network-based simulation methods, such as ordinary differential equations or Gillespie's algorithm, provided that the network is not exceedingly large. Alternatively, rule-based models can be simulated directly using particle-based kinetic Monte Carlo methods. This "network-free" approach produces exact stochastic trajectories with a computational cost that is independent of network size. However, memory and run time costs increase with the number of particles, limiting the size of system that can be feasibly simulated. Here, we present a hybrid particle/population simulation method that combines the best attributes of both the network-based and network-free approaches. The method takes as input a rule-based model and a user-specified subset of species to treat as population variables rather than as particles. The model is then transformed by a process of "partial network expansion" into a dynamically equivalent form that can be simulated using a population-adapted network-free simulator. The transformation method has been implemented within the open-source rule-based modeling platform BioNetGen, and resulting hybrid models can be simulated using the particle-based simulator NFsim. Performance tests show that significant memory savings can be achieved using the new approach and a monetary cost analysis provides a practical measure of its utility. © 2014 Hogg et al
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