MSMBuilder2: Modeling Conformational Dynamics at the Picosecond to Millisecond Scale

Markov State Models provide a framework for understanding the fundamental states and rates in the conformational dynamics of biomolecules. We describe an improved protocol for constructing Markov State Models from molecular dynamics simulations. The new protocol includes advances in clustering, data preparation, and model estimation; these improvements lead to significant increases in model accuracy, as assessed by the ability to recapitulate equilibrium and kinetic properties of reference systems. A high-performance implementation of this protocol, provided in MSMBuilder2, is validated on dynamics ranging from picoseconds to milliseconds.     

Skin: the ultimate interface

The outer layer of the skin, the stratum corneum is a unique barrier membrane. On average it is only 20 μm thick (about a quarter the thickness of a normal sheet of paper) but it prevents us from losing excessive water and it protects us from our environment. It forms a special interface between our body, the air, water and various solids. In order to understand the barrier properties of the skin we need to determine its structure at various levels ranging from the macroscopic scale to the molecular level. This has been made easier by the advances that there have been over the recent decade. However, the amount of a material that is capable of penetrating this excellent barrier and reaching the underlying systemic circulation is still only of the order of 1 or 2 per cent of the total applied dose. The purpose of this publication is to explore the strategies currently employed to promote skin permeation and to consider the most exciting approaches currently under investigation. The limitations of current methodology to examine the problem are discussed. New opportunities to fill the gaps in our current knowledge are identified and the importance of interdisciplinary research in the field is emphasised.     

Parylene insulated probes for scanning electrochemical-atomic force microscopy

Scanning electrochemical-atomic force microscopy (SECM-AFM) is a powerful technique that can be used to obtain in situ information related to electrochemical phenomena at interfaces. Fabrication of probes to perform SECM-AFM experiments remains a challenge. Herein, we describe a method for formation of microelectrodes at the tip of commercial conductive AFM probes and demonstrate application of these probes to SECM-AFM. Probes were first insulated with a thin parylene layer, followed by subsequent exposure of active electrodes at the probe tips by mechanical abrasion of the insulating layer. Characterization of probes was performed by electron microscopy and cyclic voltammetry. In situ measurement of localized electrochemical activity with parylene-coated probes was demonstrated through measurement of the diffusion of Ru(NH)(6)(3+) across a porous membrane.     

Precision measurement of neutrino oscillation parameters with KamLAND

The KamLAND experiment has determined a precise value for the neutrino oscillation parameter Deltam21(2) and stringent constraints on theta12. The exposure to nuclear reactor antineutrinos is increased almost fourfold over previous results to 2.44 x 10(32) proton yr due to longer livetime and an enlarged fiducial volume. An undistorted reactor nu[over]e energy spectrum is now rejected at >5sigma. Analysis of the reactor spectrum above the inverse beta decay energy threshold, and including geoneutrinos, gives a best fit at Deltam21(2)=7.58(-0.13)(+0.14)(stat) -0.15+0.15(syst) x 10(-5) eV2 and tan2theta12=0.56(-0.07)+0.10(stat) -0.06+0.10(syst). Local Deltachi2 minima at higher and lower Deltam21(2) are disfavored at >4sigma. Combining with solar neutrino data, we obtain Deltam21(2)=7.59(-0.21)+0.21 x 10(-5) eV2 and tan2theta12=0.47(-0.05)+0.06.     

On the character of three 8+ states in 192Pb

Three low-lying 8⁺ states have been identified in ¹⁹²Pb . A newly observed cascade of $ \gamma$ -rays built directly on the 8⁺ ₁ state is compared to the previously identified, weakly rotational band above the 11^- $ \pi$ i _13/2 , h _9/2 isomer in the same nucleus, and to analogous structures in ¹⁹⁴Pb . The similarity of all four structures lends support to the suggestion that the 8⁺ ₁ configurations are of a similar oblate deformation to the 11^- isomers. The excitation energies of all three 8⁺ states in ¹⁹²Pb and ¹⁹⁰Pb are compared to systematics. The possibility that one of the 8⁺ states in ¹⁹²Pb is associated with a prolate shape is discounted.