Targeted free energy perturbation

A generalization of the free energy perturbation identity is derived, and a computational strategy based on this result is presented. A simple example illustrates the efficiency gains that can be achieved with this method.Comment: 8 pages + 1 color figur

Fourier Acceleration of Langevin Molecular Dynamics

Fourier acceleration has been successfully applied to the simulation of lattice field theories for more than a decade. In this paper, we extend the method to the dynamics of discrete particles moving in continuum. Although our method is based on a mapping of the particles' dynamics to a regular grid so that discrete Fourier transforms may be taken, it should be emphasized that the introduction of the grid is a purely algorithmic device and that no smoothing, coarse-graining or mean-field approximations are made. The method thus can be applied to the equations of motion of molecular dynamics (MD), or its Langevin or Brownian variants. For example, in Langevin MD simulations our acceleration technique permits a straightforward spectral decomposition of forces so that the long-wavelength modes are integrated with a longer time step, thereby reducing the time required to reach equilibrium or to decorrelate the system in equilibrium. Speedup factors of up to 30 are observed relative to pure (unaccelerated) Langevin MD. As with acceleration of critical lattice models, even further gains relative to the unaccelerated method are expected for larger systems. Preliminary results for Fourier-accelerated molecular dynamics are presented in order to illustrate the basic concepts. Possible extensions of the method and further lines of research are discussed.Comment: 11 pages, two illustrations included using graphic

Dual function of rare earth carboxylate compounds on the barrier properties and active corrosion inhibition of epoxy coatings on mild steel

In this work, two rare earth carboxylate compounds, lanthanum 4-hydroxycinnamate (La(4-OHcin)3) and yttrium 3-(4-methylbenzoyl)propanoate (Y(mbp)3), were incorporated into bisphenol-based epoxy resin to investigate their effectiveness in coating barrier properties and active corrosion inhibition. EIS results showed that the incorporation of rare earth carboxylate inhibitors significantly improved corrosion resistance compared to the inhibitor free coating, with the global impedance modulus remaining at a level higher than 1 GΩ cm2 after 219 days immersion. Following EIS experiments, cross-sectional views of the coatings exhibited a pore-plugging behavior by rare earth containing precipitates, which reinforced the coating barrier properties and delayed the electrolyte diffusion process. These effects were also reflected from the electrochemical parameters extracted from breakpoint frequency analysis and equivalent circuit modelling. Filiform corrosion experiments for artificially scratched coatings suggest that the addition of rare earth carboxylates effectively suppressed the initiation and growth of filaments as well as the development of the coating delamination front. The active corrosion inhibition is possibly related to the formation of a surface protective film consisting of bimetallic complexes and rare earth metal rich precipitates. The electrochemical measurements and surface analyses evidence the dual function of rare earth carboxylate species for enhancing coating barrier properties against electrolyte penetration and providing active corrosion inhibition for the underlying AS1020 mild steel

The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for maintaining cellular energy homeostasis. Activation of AMPK by salicylate and the thienopyridone A-769662 is critically dependent on phosphorylation of Ser108 in the β1 regulatory subunit. Here, we show a possible role for Ser108 phosphorylation in cell cycle regulation and promotion of pro-survival pathways in response to energy stress. We identify the autophagy initiator Unc-51-like kinase 1 (ULK1) as a β1-Ser108 kinase in cells. Cellular β1-Ser108 phosphorylation by ULK1 was dependent on AMPK β-subunit myristoylation, metabolic stress associated with elevated AMP/ATP ratio, and the intrinsic energy sensing capacity of AMPK; features consistent with an AMP-induced myristoyl switch mechanism. We further demonstrate cellular AMPK signaling independent of activation loop Thr172 phosphorylation, providing potential insight into physiological roles for Ser108 phosphorylation. These findings uncover new mechanisms by which AMPK could potentially maintain cellular energy homeostasis independently of Thr172 phosphorylation

Study of Effect on Teeth of Intermittent Fluoridation of a Community Water Supply

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67913/2/10.1177_00220345530320011601.pd

Microwave heating, isothermal sintering, and mechanical properties of powder metallurgy titanium and titanium alloys

This article presents a detailed assessment of microwave (MW) heating, isothermal sintering, and the resulting tensile properties of commercially pure Ti (CP-Ti), Ti-6Al-4V, and Ti-10V-2Fe-3Al (wt pct), by comparison with those fabricated by conventional vacuum sintering. The potential of MW sintering for titanium fabrication is evaluated accordingly. Pure MW radiation is capable of heating titanium powder to ≥1573 K (1300 C), but the heating response is erratic and difficult to reproduce. In contrast, the use of SiC MW susceptors ensures rapid, consistent, and controllable MW heating of titanium powder. MW sintering can consolidate CP-Ti and Ti alloys compacted from -100 mesh hydride-dehydride (HDH) Ti powder to ~95.0 pct theoretical density (TD) at 1573 K (1300 C), but no accelerated isothermal sintering has been observed over conventional practice. Significant interstitial contamination occurred from the Al2O3-SiC insulation-susceptor package, despite the high vacuum used (≤4.0 × 10-3 Pa). This leads to erratic mechanical properties including poor tensile ductility. The use of Ti sponge as impurity (O, N, C, and Si) absorbers can effectively eliminate this problem and ensure good-to-excellent tensile properties for MW-sintered CP-Ti, Ti-10V-2Fe-3Al, and Ti-6Al-4V. The mechanisms behind various observations are discussed. The prime benefit of MW sintering of Ti powder is rapid heating. MW sintering of Ti powder is suitable for the fabrication of small titanium parts or titanium preforms for subsequent thermomechanical processing