Monodisperse self-assembly in a model with protein-like interactions

We study the self-assembly behaviour of patchy particles with `protein-like' interactions that can be considered as a minimal model for the assembly of viral capsids and other shell-like protein complexes. We thoroughly explore the thermodynamics and dynamics of self assembly as a function of the parameters of the model and find robust assembly of all target structures considered. Optimal assembly occurs in the region of parameter space where a free energy barrier regulates the rate of nucleation, thus preventing the premature exhaustion of the supply of monomers that can lead to the formation of incomplete shells. The interactions also need to be specific enough to prevent the assembly of malformed shells, but whilst maintaining kinetic accessibility. Free-energy landscapes computed for our model have a funnel-like topography guiding the system to form the target structure, and show that the torsional component of the interparticle interactions prevents the formation of disordered aggregates that would otherwise act as kinetic traps.Comment: 11 pages; 10 figure

Reversible self-assembly of patchy particles into monodisperse icosahedral clusters

We systematically study the design of simple patchy sphere models that reversibly self-assemble into monodisperse icosahedral clusters. We find that the optimal patch width is a compromise between structural specificity (the patches must be narrow enough to energetically select the desired clusters) and kinetic accessibility (they must be sufficiently wide to avoid kinetic traps). Similarly, for good yields the temperature must be low enough for the clusters to be thermodynamically stable, but the clusters must also have enough thermal energy to allow incorrectly formed bonds to be broken. Ordered clusters can form through a number of different dynamic pathways, including direct nucleation and indirect pathways involving large disordered intermediates. The latter pathway is related to a reentrant liquid-to-gas transition that occurs for intermediate patch widths upon lowering the temperature. We also find that the assembly process is robust to inaccurate patch placement up to a certain threshold, and that it is possible to replace the five discrete patches with a single ring patch with no significant loss in yield.Comment: 12 pages, 12 figure

Foreshock density holes in the context of known upstream plasma structures

We present case examples of foreshock density holes and results from a statistical survey, which provide additional characterizations of these recently-described structures. Specific effort is made to place these objects into context with well-studied foreshock phenomena, such as hot flow anomalies (HFAs) and large-amplitude magnetic pulsations (SLAMS). Density holes are observed during higher-than-average solar wind speeds (~620 km s<sup>−1</sup>), have well-correlated density and magnetic field intensities, and anti-correlated density and temperature variations. Like HFAs, these structures occur over a wide range of foreshock geometries, suggesting that this is not a determining factor. They are embedded within IMF current sheets, but their cross-structure magnetic shears are considerably lower than for HFAs. When the Cluster spacecraft are widely separated, they are able to measure structure time development, with substantial changes occurring over 10s of seconds, confirming an earlier case study, and possibly indicating short lifetimes as well. We find that density holes can occur in the absence of strong upstream magnetic pulsations and/or density enhancements, which rules out a "wake effect" as the sole explanation for their formation. Most important is the observation that the observed solar wind motional electric fields tend to have components pointing away from the embedding IMF current sheets. Density holes have no connection with magnetic holes and foreshock cavities, and appear not to be early-stage or weakly-formed HFAs

Klebsiella pneumoniae carbapenamases in Escherichia coli isolated from humans and livestock in rural South-Western Uganda

Funding: This work was supported by; The "Holistic Approach to Unravel Antibacterial Resistance in East Africa” project which was a 3-year Global Context Consortia Award (MR/S004785/1) funded by the National Institute for Health Research, Medical Research Council and the Department of Health and Social Care, UK.Background The accumulation of resistance genes in Escherichia coli (E. coli) strains imposes limitations in the therapeutic options available for the treatment of infections caused by E.coli. Production of Klebsiella pneumoniae carbapenemase (KPC) by E. coli renders it resistant to broad-spectrum β-lactam antibiotics. Globally there is existing evidence of spread of carbapenem-resistant E. coli in both humans and livestock driven by acquisition of the several other carbapenemase genes. Overall, there is little information regarding the extent of KPC gene distribution in E. coli. We set out to determine the prevalence, and evaluate the phenotypic and genotypic patterns of KPC in E. coli isolated from humans and their livestock in rural south western Uganda. Methods A laboratory-based, descriptive cross-sectional study was conducted involving 96 human and 96 livestock isolates collected from agro-pastoralist communities in Mbarara district in south western Uganda. Phenotypic and molecular methods (PCR) were used for presence and identification of KPC genes in the E. coli isolates. A chi-square test of independence was used to evaluate the differences in resistant patterns between carbapenems and isolates. Results The overall prevalence of carbapenem resistance by disk diffusion susceptibility testing (DST) for both humans and livestock isolates were 41.7% (80/192). DST-based resistance was identical in both human and livestock isolates (41.7%). The prevalence of carbapenem resistance based on Modified Hodge Test (MHT) was 5% (2/40) and 10% (4/40) for humans and livestock isolates respectively. Both human and livestock isolates, 48.7% (95/192) had the KPC gene, higher than phenotypic expression; 41.7% (80/192). blaKPC gene prevalence was overall similar in human isolates (51%; 49/96) vs livestock isolates (47.9%; 46/96). Approximately, 19% (15/80) of the isolates were phenotypically resistant to carbapenems and over 70% (79/112) of the phenotypically sensitive strains harbored the blaKPC gene. Conclusion Our results suggest that both human and livestock isolates of E. coli in our setting carry the blaKPC gene with a high percentage of strains not actively expressing the blaKPC gene. The finding of fewer isolates carrying the KPC gene than those phenotypically resistant to carbapenems suggests that other mechanisms are playing a role in this phenomenon, calling for further researcher into this phenomenon.Publisher PDFPeer reviewe

The self-assembly and evolution of homomeric protein complexes

We introduce a simple "patchy particle" model to study the thermodynamics and dynamics of self-assembly of homomeric protein complexes. Our calculations allow us to rationalize recent results for dihedral complexes. Namely, why evolution of such complexes naturally takes the system into a region of interaction space where (i) the evolutionarily newer interactions are weaker, (ii) subcomplexes involving the stronger interactions are observed to be thermodynamically stable on destabilization of the protein-protein interactions and (iii) the self-assembly dynamics are hierarchical with these same subcomplexes acting as kinetic intermediates.Comment: 4 pages, 4 figure

In pursuit of the dynamic optimality conjecture

In 1985, Sleator and Tarjan introduced the splay tree, a self-adjusting binary search tree algorithm. Splay trees were conjectured to perform within a constant factor as any offline rotation-based search tree algorithm on every sufficiently long sequence---any binary search tree algorithm that has this property is said to be dynamically optimal. However, currently neither splay trees nor any other tree algorithm is known to be dynamically optimal. Here we survey the progress that has been made in the almost thirty years since the conjecture was first formulated, and present a binary search tree algorithm that is dynamically optimal if any binary search tree algorithm is dynamically optimal.Comment: Preliminary version of paper to appear in the Conference on Space Efficient Data Structures, Streams and Algorithms to be held in August 2013 in honor of Ian Munro's 66th birthda

Annual Cycle of Cloud Forcing of Surface Radiation Budget

The climate of the Earth is determined by its balance of radiation. The incoming and outgoing radiation fluxes are strongly modulated by clouds, which are not well understood. The Earth Radiation Budget Experiment (Barkstrom and Smith, 1986) provided data from which the effects of clouds on radiation at the top of the atmosphere (TOA) could be computed (Ramanathan, 1987). At TOA, clouds increase the reflected solar radiation, tending to cool the planet, and decrease the OLR, causing the planet to retain its heat (Ramanathan et al., 1989; Harrison et al., 1990). The effects of clouds on radiation fluxes are denoted cloud forcing. These shortwave and longwave forcings counter each other to various degrees, so that in the tropics the result is a near balance. Over mid and polar latitude oceans, cloud forcing at TOA results in large net loss of radiation. Here, there are large areas of stratus clouds and cloud systems associated with storms. These systems are sensitive to surface temperatures and vary strongly with the annual cycle. During winter, anticyclones form over the continents and move to the oceans during summer. This movement of major cloud systems causes large changes of surface radiation, which in turn drives the surface temperature and sensible and latent heat released to the atmosphere

Evaluating Surface Flux Results from CERES-FLASHFlux

The Fast Longwave and Shortwave Radiative Flux (FLASHFlux) data product was developed to provide a rapid release version of the Clouds and Earth's Radiant Energy System (CERES) results, which could be made available to the research and applications communities within one week of the satellite observations by exchanging some accuracy for speed of processing. Unlike standard CERES products, FLASHFlux does not maintain a long-term consistent record. Therefore the latest algorithm changes and input data can be incorporated into processing. FLASHFlux released Version3A (January 2013) and Version 3B (August 2014) which include the latest meteorological product from Global Modeling and Assimilation Office (GMAO), GEOS FP-IT (5.9.1), the latest spectral response functions and gains for the CERES instruments, and aerosol climatology based on the latest MATCH data. Version 3B included a slightly updated calibration and some changes to the surface albedo over snow/ice. Typically FLASHFlux does not reprocess earlier versions when a new version is released. The combined record of Time Interpolated Space Averaged (TISA) surface flux results from Versions3A and 3B for July 2012 to October 2015 have been compared to the ground-based measurements. The FLASHFlux results are also compared to two other CERES gridded products, SYN1deg and EBAF surface fluxes