Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes

Nonlinear Dynamics of 3D Massive Gravity

We explore the nonlinear classical dynamics of the three-dimensional theory of "New Massive Gravity" proposed by Bergshoeff, Hohm and Townsend. We find that the theory passes remarkably highly nontrivial consistency checks at the nonlinear level. In particular, we show that: (1) In the decoupling limit of the theory, the interactions of the helicity-0 mode are described by a single cubic term -- the so-called cubic Galileon -- previously found in the context of the DGP model and in certain 4D massive gravities. (2) The conformal mode of the metric coincides with the helicity-0 mode in the decoupling limit. Away from this limit the nonlinear dynamics of the former is described by a certain generalization of Galileon interactions, which like the Galileons themselves have a well-posed Cauchy problem. (3) We give a non-perturbative argument based on the presence of additional symmetries that the full theory does not lead to any extra degrees of freedom, suggesting that a 3D analog of the 4D Boulware-Deser ghost is not present in this theory. Last but not least, we generalize "New Massive Gravity" and construct a class of 3D cubic order massive models that retain the above properties.Comment: 21 page

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

Comparisons between MHD model calculations and observations of Cassini flybys of Titan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94689/1/jgra18227.pd

Lattice-gas simulations of Domain Growth, Saturation and Self-Assembly in Immiscible Fluids and Microemulsions

We investigate the dynamical behavior of both binary fluid and ternary microemulsion systems in two dimensions using a recently introduced hydrodynamic lattice-gas model of microemulsions. We find that the presence of amphiphile in our simulations reduces the usual oil-water interfacial tension in accord with experiment and consequently affects the non-equilibrium growth of oil and water domains. As the density of surfactant is increased we observe a crossover from the usual two-dimensional binary fluid scaling laws to a growth that is {\it slow}, and we find that this slow growth can be characterized by a logarithmic time scale. With sufficient surfactant in the system we observe that the domains cease to grow beyond a certain point and we find that this final characteristic domain size is inversely proportional to the interfacial surfactant concentration in the system.Comment: 28 pages, latex, embedded .eps figures, one figure is in colour, all in one uuencoded gzip compressed tar file, submitted to Physical Review