Stability analysis of gravity-driven infiltrating flow

[1] Stability analysis of gravity-driven unsaturated flow is examined for the general case of Darcian flow with a generalized nonequilibrium capillary pressure-saturation relation. With this nonequilibrium relation the governing equation is referred to as the nonequilibrium Richards equation (NERE). For the special case where the nonequilibrium vanishes, the NERE reduces to the Richards equation (RE), the conventional governing equation for describing unsaturated flow. A generalized linear stability analysis of the RE shows that this equation is unconditionally stable and therefore not able to produce gravity-driven unstable flows for infinitesimal perturbations to the flow field. A much stronger result of unconditional stability for the RE is derived using a nonlinear stability analysis applicable to the general case of heterogeneous porous media. For the general case of the NERE model, results of a linear stability analysis show that the NERE model is conditionally stable, with lower-frequency perturbations being unstable. A result of this analysis is that the nonmonotonicity of the pressure and saturation profile is a requisite condition for flow instability

Utilising stream reasoning techniques to underpin an autonomous framework for cloud application platforms

As cloud application platforms (CAPs) are reaching the stage where the human effort required to maintain them at an operational level is unsupportable, one of the major challenges faced by the cloud providers is to develop appropriate mechanisms for run-time monitoring and adaptation, to prevent cloud application platforms from quickly dissolving into a non-reliable environment. In this context, the application of intelligent approaches to Autonomic Clouds may offer promising opportunities. In this paper we present an approach to providing cloud platforms with autonomic capabilities, utilising techniques from the Semantic Web and Stream Reasoning research fields. The main idea of this approach is to encode values, monitored within cloud application platforms, using Semantic Web languages, which then allows us to integrate semantically-enriched observation streams with static ontological knowledge and apply intelligent reasoning. Using such run-time reasoning capabilities, we have developed a conceptual architecture for an autonomous framework and describe a prototype solution we have constructed which implements this architecture. Our prototype is able to perform analysis and failure diagnosis, and suggest further adaptation actions. We report our experience in utilising the Stream Reasoning technique in this context as well as further challenges that arise out of our work

Nitrite circumvents platelet resistance to nitric oxide in patients with heart failure preserved ejection fraction and chronic atrial fibrillation

Aims: Heart failure (HF) is a pro-thrombotic state. Both platelet and vascular responses to nitric oxide (NO) donors are impaired in HF patients with reduced ejection fraction (HFrEF) compared to healthy volunteers (HV) due to scavenging of NO, and possibly also reduced activity of the principal NO sensor, soluble guanylate cyclase (sGC), limiting the therapeutic potential of NO donors as anti-aggregatory agents. Previous studies have shown that nitrite inhibits platelet activation presumptively after its reduction to NO, but the mechanism(s) involved remain poorly characterized. Our aim was to compare the effects of nitrite on platelet function in HV vs. HF patients with preserved ejection fraction (HFpEF) and chronic atrial fibrillation (HFpEF-AF), vs. patients with chronic AF without HF, and to assess whether these effects occur independent of the interaction with other formed elements of blood. Methods and Results: Platelet responses to nitrite and the NO donor sodium nitroprusside (SNP) were compared in age-matched HV controls (n = 12), HFpEF-AF patients (n = 29) and chronic AF patients (n = 8). Anti-aggregatory effects of nitrite in the presence of NO scavengers/sGC inhibitor were determined and vasodilator-stimulated phosphoprotein (VASP) phosphorylation was assessed using Western blotting. In HV and chronic AF, both nitrite and SNP inhibited platelet aggregation in a concentration-dependent manner. Inhibition of platelet aggregation by the NO donor SNP was impaired in HFpEF-AF patients compared to healthy and chronic AF individuals, but there was no impairment of the anti-aggregatory effects of nitrite. Nitrite circumvented platelet NO resistance independently of other blood cells by directly activating sGC and phosphorylating VASP. Conclusion: We here show for the first time that HFpEF-AF (but not chronic AF without HF) is associated with marked impairment of platelet NO responses due to sGC dysfunction and nitrite circumvents the “platelet NO resistance” phenomenon in human HFpEF, at least partly, by acting as a direct sGC activator independent of NO

The nitric oxide redox sibling nitroxyl partially circumvents impairment of platelet nitric oxide responsiveness

Impaired platelet responsiveness to nitric oxide (NO resistance) is a common characteristic of many cardiovascular disease states and represents an independent risk factor for cardiac events and mortality. NO resistance reflects both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor, soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO, produces vasodilator and anti-aggregatory effects, largely via sGC activation, but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO resistance in human platelets. In 57 subjects with or without ischemic heart disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and the NO donor sodium nitroprusside (SNP) were compared. While SNP (10μM) induced 29±3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10μM) caused 75±4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response ratio was markedly increased (p<0.01), consistent with partial circumvention of NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001) with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO, 200μM) inhibited SNP and IPA/NO responses by 92±7% and 17±4% respectively (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only partially NO-mediated. ODQ (10μM) inhibited IPA/NO responses by 36±8% (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of aggregation. There was no significant relationship between whole blood ROS content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents platelet NO resistance while acting, at least partially, as a haem-mediated sGC activator.R.F. Dautov, D.T.M. Ngo, G. Licari, S. Liu, A.L. Sverdlov, R.H. Ritchie, B.K. Kemp-Harper, J.D. Horowitz, Y.Y. Chirko