Stimulation of multiple mitogen-activated protein kinase sub-families by oxidative stress and phosphorylation of the small heat shock protein, HSP25/27, in neonatal ventricular myocytes.

We investigated the activation of three subfamilies of mitogen-activated protein kinases (MAPKs), namely the stress-activated protein kinases/c-Jun N-terminal kinases (SAPKs/JNKs), the extracellularly responsive kinases (ERKs) and p38-MAPK, by oxidative stress as exemplified by H2O2 in primary cultures of neonatal rat ventricular myocytes. The 46 and 54 kDa species of SAPKs/JNKs were activated 5- and 10-fold, respectively, by 0.1 mM H2O2 (the maximally effective concentration). Maximal activation occurred at 15-30 min, but was still detectable after 2 h. Both ERK1 and ERK2 were activated 16-fold by 0.1 mM H2O2 with a similar time course to the SAPKs/JNKs, and this was comparable with their activation by 1 microM PMA, the most powerful activator of ERKs that we have so far identified in these cells. The activation of ERKs by H2O2 was inhibited by PD98059, which inhibits the activation of MAPK (or ERK) kinases, and by the protein kinase C (PKC) inhibitor, GF109203X. ERK activation was also inhibited by down-regulation of PMA-sensitive PKC isoforms. p38-MAPK was activated by 0.1 mM H2O2 as shown by an increase in its phosphorylation. However, maximal phosphorylation (activation) was more rapid (<5 min) than for the SAPKs/JNKs or the ERKs. We studied the downstream consequences of p38-MAPK activation by examining activation of MAPK-activated protein kinase 2 (MAPKAPK2) and phosphorylation of the MAPKAPK2 substrate, the small heat shock protein HSP25/27. As with p38-MAPK, MAPKAPK2 was rapidly activated (maximal within 5 min) by 0.1 mM H2O2. This activation was abolished by 10 microM SB203580, a selective inhibitor of certain p38-MAPK isoforms. The phosphorylation of HSP25/27 rapidly followed activation of MAPKAPK2 and was also inhibited by SB203580. Phosphorylation of HSP25/27 was associated with a decrease in its aggregation state. These data indicate that oxidative stress is a powerful activator of all three MAPK subfamilies in neonatal rat ventricular myocytes. Activation of all three MAPKs has been associated with the development of the hypertrophic phenotype. However, stimulation of p38-MAPK and the consequent phosphorylation of HSP25/27 may also be important in cardioprotection.

Symmetric Push-Sum Protocol for decentralised aggregation

Gossip (or Epidemic) protocols have emerged as a communication and computation paradigm for large-scale networked systems. These protocols are based on randomised communication, which provides probabilistic guarantees on convergence speed and accuracy. They also provide robustness, scalability, computational and communication efficiency and high stability under disruption. This work presents a novel Gossip protocol named Symmetric Push-Sum Protocol for the computation of global aggregates (e.g., average) in decentralised and asynchronous systems. The proposed approach combines the simplicity of the push-based approach and the efficiency of the push-pull schemes. The push-pull schemes cannot be directly employed in asynchronous systems as they require synchronous paired communication operations to guarantee their accuracy. Although push schemes guarantee accuracy even with asynchronous communication, they suffer from a slower and unstable convergence. Symmetric Push- Sum Protocol does not require synchronous communication and achieves a convergence speed similar to the push-pull schemes, while keeping the accuracy stability of the push scheme. In the experimental analysis, we focus on computing the global average as an important class of node aggregation problems. The results have confirmed that the proposed method inherits the advantages of both other schemes and outperforms well-known state of the art protocols for decentralized Gossip-based aggregation.

Reversible state transition in nanoconfined aqueous solutions

Using molecular dynamics simulations, we find a reversible transition between the dispersion and aggregation states of solute molecules in aqueous solutions confined in nanoscale geometry, which is not observed in macroscopic systems. The nanoscale confinement also leads to a significant increase of the critical aggregation concentration (CAC). A theoretical model based on Gibbs free energy calculation is developed to describe the simulation results. It indicates that the reversible state transition is attributed to the low free energy barrier (of order kBT) in between two energy minima corresponding to the dispersion and aggregation states, and the enhancement of the CAC results from the fact that at lower concentrations the number of solute molecules is not large enough to allow the formation of a stable cluster in the confined systems.

The sensitivity of convective aggregation to diabatic processes in idealized radiative-convective equilibrium simulations

Idealized explicit convection simulations of the Met Office Unified Model exhibit spontaneous self-aggregation in radiative-convective equilibrium, as seen in other models in previous studies. This self-aggregation is linked to feedbacks between radiation, surface fluxes, and convection, and the organization is intimately related to the evolution of the column water vapor field. Analysis of the budget of the spatial variance of column-integrated frozen moist static energy (MSE), following Wing and Emanuel [2014], reveals that the direct radiative feedback (including significant cloud longwave effects) is dominant in both the initial development of self-aggregation and the maintenance of an aggregated state. A low-level circulation at intermediate stages of aggregation does appear to transport MSE from drier to moister regions, but this circulation is mostly balanced by other advective effects of opposite sign and is forced by horizontal anomalies of convective heating (not radiation). Sensitivity studies with either fixed prescribed radiative cooling, fixed prescribed surface fluxes, or both do not show full self-aggregation from homogeneous initial conditions, though fixed surface fluxes do not disaggregate an initialized aggregated state. A sensitivity study in which rain evaporation is turned off shows more rapid self-aggregation, while a run with this change plus fixed radiative cooling still shows strong self-aggregation, supporting a “moisture memory” effect found in Muller and Bony [2015]. Interestingly, self-aggregation occurs even in simulations with sea surface temperatures (SSTs) of 295 K and 290 K, with direct radiative feedbacks dominating the budget of MSE variance, in contrast to results in some previous studies.