Effect of Cluster Formation on Isospin Asymmetry in the Liquid-Gas Phase Transition Region

Nuclear matter within the liquid-gas phase transition region is investigated in a mean-field two-component Fermi-gas model. Following largely analytic considerations, it is shown that: (1) Due to density dependence of asymmetry energy, some of the neutron excess from the high-density phase could be expelled into the low-density region. (2) Formation of clusters in the gas phase tends to counteract this trend, making the gas phase more liquid-like and reducing the asymmetry in the gas phase. Flow of asymmetry between the spectator and midrapidity region in reactions is discussed and a possible inversion of the flow direction is indicated.Comment: 9 pages,3 figures, RevTe

Disease-Associated Mutations Disrupt Functionally Important Regions of Intrinsic Protein Disorder

The effects of disease mutations on protein structure and function have been extensively investigated, and many predictors of the functional impact of single amino acid substitutions are publicly available. The majority of these predictors are based on protein structure and evolutionary conservation, following the assumption that disease mutations predominantly affect folded and conserved protein regions. However, the prevalence of the intrinsically disordered proteins (IDPs) and regions (IDRs) in the human proteome together with their lack of fixed structure and low sequence conservation raise a question about the impact of disease mutations in IDRs. Here, we investigate annotated missense disease mutations and show that 21.7% of them are located within such intrinsically disordered regions. We further demonstrate that 20% of disease mutations in IDRs cause local disorder-to-order transitions, which represents a 1.7–2.7 fold increase compared to annotated polymorphisms and neutral evolutionary substitutions, respectively. Secondary structure predictions show elevated rates of transition from helices and strands into loops and vice versa in the disease mutations dataset. Disease disorder-to-order mutations also influence predicted molecular recognition features (MoRFs) more often than the control mutations. The repertoire of disorder-to-order transition mutations is limited, with five most frequent mutations (R→W, R→C, E→K, R→H, R→Q) collectively accounting for 44% of all deleterious disorder-to-order transitions. As a proof of concept, we performed accelerated molecular dynamics simulations on a deleterious disorder-to-order transition mutation of tumor protein p63 and, in agreement with our predictions, observed an increased α-helical propensity of the region harboring the mutation. Our findings highlight the importance of mutations in IDRs and refine the traditional structure-centric view of disease mutations. The results of this study offer a new perspective on the role of mutations in disease, with implications for improving predictors of the functional impact of missense mutations

A Suite of Early Eocene (~55 Ma) Climate Model Boundary Conditions

We describe a set of early Eocene (~ 55 Ma) climate model boundary conditions constructed in a self-consistent reference frame and incorporating recent data and methodologies. Given the growing need for uniform experimental design within the Eocene climate modelling community and the challenges faced in simulating the prominent features of Eocene climate, we make publicly available our data sets of Eocene topography, bathymetry, tidal dissipation, vegetation, aerosol distributions and river runoff. Major improvements in our boundary conditions over previous efforts include the implementation of the ANTscape palaeotopography of Antarctica, more accurate representations of the Drake Passage and Tasman Gateway, as well as an approximation of sub grid cell topographic variability. Our boundary conditions also include for the first time modelled estimates of Eocene aerosol distributions and tidal dissipation, both consistent with our palaeotopography and palaeobathymetry. The resolution of our data sets is unprecedented and will facilitate high resolution climate simulations. In light of the inherent uncertainties involved in reconstructing global boundary conditions for past time periods these data sets should be considered as one interpretation of the available data and users are encouraged to modify them according to their needs and interpretations. This paper marks the beginning of a process for reconstructing a set of accurate, open-access Eocene boundary conditions for use in climate models

Cooling and Instabilities in Colliding Radiative Flows with Toroidal Magnetic Fields

We report on the results of a simulation based study of colliding magnetized plasma flows. Our set-up mimics pulsed power laboratory astrophysical experiments but, with an appropriate frame change, are relevant to astrophysical jets with internal velocity variations. We track the evolution of the interaction region where the two flows collide. Cooling via radiative loses are included in the calculation. We systematically vary plasma beta ($\beta_m$) in the flows, the strength of the cooling ($\Lambda_0$) and the exponent ($\alpha$) of temperature-dependence of the cooling function. We find that for strong magnetic fields a counter-propagating jet called a "spine" is driven by pressure from shocked toroidal fields. The spines eventually become unstable and break apart. We demonstrate how formation and evolution of the spines depends on initial flow parameters and provide a simple analytic model that captures the basic features of the flow.Comment: 14 pages, 16 figures. Submitted to MNRA

Morphology of Shocked Lateral Outflows in Colliding Hydrodynamic Flows

Supersonic interacting flows occurring in phenomena such as protostellar jets give rise to strong shocks, and have been demonstrated in several laboratory experiments. To study such colliding flows, we use the AstroBEAR AMR code to conduct hydrodynamic simulations in three dimensions. We introduce variations in the flow parameters of density, velocity, and cross sectional radius of the colliding flows %radius in order to study the propagation and conical shape of the bow shock formed by collisions between two, not necessarily symmetric, hypersonic flows. We find that the motion of the interaction region is driven by imbalances in ram pressure between the two flows, while the conical structure of the bow shock is a result of shocked lateral outflows (SLOs) being deflected from the horizontal when the flows are of differing cross-section

Climate sensitivity on geological timescales controlled by nonlinear feedbacks and ocean circulation

Climate sensitivity is a key metric used to assess the magnitude of global warming given 19 increased CO2 concentrations. The geological past can provide insights into climate sensitivity; however, on timescales of millions of years, factors other than CO2 can drive climate, including paleogeographic forcing and solar luminosity. Here, through an ensemble of climate model simulations covering the period 150-35 million years ago, we show that climate sensitivity to CO2 doubling varies between ∼3.5-5.5◦ C through this time. These variations can be explained as a non-linear response to solar luminosity, evolving surface albedo due to changes in ocean area, and changes in ocean circulation. The work shows that the modern climate sensitivity is relatively low in the context of the geological record, as a result of relatively weak feedbacks due to a relatively low CO2 baseline, and the presence of ice and relatively small ocean area in the modern continental con figuration

Spitzer SAGE survey of the Large Magellanic Cloud II: Evolved Stars and Infrared Color Magnitude Diagrams

Color-magnitude diagrams (CMDs) are presented for the Spitzer SAGE (Surveying the Agents of a Galaxy's Evolution) survey of the Large Magellanic Cloud (LMC). IRAC and MIPS 24 um epoch one data are presented. These data represent the deepest, widest mid-infrared CMDs of their kind ever produced in the LMC. Combined with the 2MASS survey, the diagrams are used to delineate the evolved stellar populations in the Large Magellanic Cloud as well as Galactic foreground and extragalactic background populations. Some 32000 evolved stars brighter than the tip of the red giant branch are identified. Of these, approximately 17500 are classified as oxygen-rich, 7000 carbon-rich, and another 1200 as ``extreme'' asymptotic giant branch (AGB) stars. Brighter members of the latter group have been called ``obscured'' AGB stars in the literature owing to their dusty circumstellar envelopes. A large number (1200) of luminous oxygen--rich AGB stars/M supergiants are also identified. Finally, there is strong evidence from the 24 um MIPS channel that previously unexplored, lower luminosity oxygen-rich AGB stars contribute significantly to the mass loss budget of the LMC (1200 such sources are identified).Comment: LaTex, 31 pages, 10 figures. Accepted for publication in the Astronomical Journa

Enhanced Lipid Diffusion and Mixing in Accelerated Molecular Dynamics

Accelerated molecular dynamics (aMD) is an enhanced sampling technique that expedites conformational space sampling by reducing the barriers separating various low-energy states of a system. Here, we present the first application of the aMD method on lipid membranes. Altogether, ∼1.5 μs simulations were performed on three systems: a pure POPC bilayer, a pure DMPC bilayer, and a mixed POPC:DMPC bilayer. Overall, the aMD simulations are found to produce significant speedup in trans–gauche isomerization and lipid lateral diffusion versus those in conventional MD (cMD) simulations. Further comparison of a 70-ns aMD run and a 300-ns cMD run of the mixed POPC:DMPC bilayer shows that the two simulations yield similar lipid mixing behaviors, with aMD generating a 2–3-fold speedup compared to cMD. Our results demonstrate that the aMD method is an efficient approach for the study of bilayer structural and dynamic properties. On the basis of simulations of the three bilayer systems, we also discuss the impact of aMD parameters on various lipid properties, which can be used as a guideline for future aMD simulations of membrane systems

On the Use of Accelerated Molecular Dynamics to Enhance Configurational Sampling in Ab Initio Simulations

We have implemented the accelerated molecular dynamics approach (Hamelberg, D.; Mongan, J.; McCammon, J. A. J. Chem. Phys. 2004, 120 (24), 11919) in the framework of ab initio MD (AIMD). Using three simple examples, we demonstrate that accelerated AIMD (A-AIMD) can be used to accelerate solvent relaxation in AIMD simulations and facilitate the detection of reaction coordinates: (i) We show, for one cyclohexane molecule in the gas phase, that the method can be used to accelerate the rate of the chair-to-chair interconversion by a factor of ∼1 × 105, while allowing for the reconstruction of the correct canonical distribution of low-energy states; (ii) We then show, for a water box of 64 H2O molecules, that A-AIMD can also be used in the condensed phase to accelerate the sampling of water conformations, without affecting the structural properties of the solvent; and (iii) The method is then used to compute the potential of mean force (PMF) for the dissociation of Na−Cl in water, accelerating the convergence by a factor of ∼3−4 compared to conventional AIMD simulations.(2) These results suggest that A-AIMD is a useful addition to existing methods for enhanced conformational and phase-space sampling in solution. While the method does not make the use of collective variables superfluous, it also does not require the user to define a set of collective variables that can capture all the low-energy minima on the potential energy surface. This property may prove very useful when dealing with highly complex multidimensional systems that require a quantum mechanical treatment