Accurate Thermodynamics for Short-Ranged Truncations of Coulomb Interactions in Site-Site Molecular Models

Coulomb interactions are present in a wide variety of all-atom force fields. Spherical truncations of these interactions permit fast simulations but are problematic due to their incorrect thermodynamics. Herein we demonstrate that simple analytical corrections for the thermodynamics of uniform truncated systems are possible. In particular results for the SPC/E water model treated with spherically-truncated Coulomb interactions suggested by local molecular field theory [Proc. Nat. Acad. Sci. USA 105, 19136 (2008)] are presented. We extend results developed by Chandler [J. Chem. Phys. 65, 2925 (1976)] so that we may treat the thermodynamics of mixtures of flexible charged and uncharged molecules simulated with spherical truncations. We show that the energy and pressure of spherically-truncated bulk SPC/E water are easily corrected using exact second-moment-like conditions on long-ranged structure. Furthermore, applying the pressure correction as an external pressure removes the density errors observed by other research groups in NPT simulations of spherically-truncated bulk species

Two-photon laser-induced fluorescence detection of OH

The TP-LIF OH sensor is based on the principle that a molecule having multiple energy states, all of which are bonding, can be pumped into the highest state with the resulting fluorescence being blue-shifted relative to all pumping wavelengths. In this way, one can successfully discriminate against virtually all noise sources in the system using long wavelength blocking filters in conjunction with solar-blind photomultiplier tubes. Thus, these systems tend to be signal limited rather than signal-to-noise limited as is true of the SP-LIF technique as well as other conventional analytical methods. The trick to achieving the above sampling scheme, with high efficiency, is in the use of high photon fluxes of short time duration. Obviously, the latter type of light source is fulfilled nicely by available pulsed lasers. From an operational point of view, however, this laser source needs to be tunable. The latter characteristic permits extremely high selectivity for the detection of a diatomic or simple polyatomic molecule by taking advantage of the high-resolution spectroscopic features of these type species

Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus

Introduction ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. Methods SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. Results SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. Conclusions SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate

Synthetic 26Al emission from galactic-scale superbubble simulations

© 2019 The Author(s).Emission from the radioactive trace element 26Al has been observed throughout the Milky Way with the COMPTEL and INTEGRAL satellites. In particular the Doppler shifts measured with INTEGRAL connect 26Al with superbubbles, which may guide 26Al flows off spiral arms in the direction of Galactic rotation. In order to test this paradigm, we have performed galaxy-scale simulations of superbubbles with 26Al injection in a Milky Way-type galaxy. We produce all-sky synthetic $\gamma-$ray emission maps of the simulated galaxies. We find that the 1809keV emission from the radioactive decay of 26Al is highly variable with time and the observer's position. This allows us to estimate an additional systematic variability of 0.2dex for a star formation rate derived from 26Al for different times and measurement locations in Milky Way-type galaxies. High-latitude morphological features indicate nearby emission with correspondingly high integrated gamma-ray intensities. We demonstrate that the 26Al scale height from our simulated galaxies depends on the assumed halo gas density. We present the first synthetic 1809keV longitude-velocity diagrams from 3D hydrodynamic simulations. The line-of-sight velocities for 26Al can be significantly different from the line-of-sight velocities associated with the cold gas. Over time, 26Al velocities consistent with the INTEGRAL observations, within uncertainties, appear at any given longitude, broadly supporting previous suggestions that 26Al injected into expanding superbubbles by massive stars may be responsible for the high velocities found in the INTEGRAL observations. We discuss the effect of systematically varying the location of the superbubbles relative to the spiral arms.Peer reviewedFinal Accepted Versio

Local molecular field theory for the treatment of electrostatics

We examine in detail the theoretical underpinnings of previous successful applications of local molecular field (LMF) theory to charged systems. LMF theory generally accounts for the averaged effects of long-ranged components of the intermolecular interactions by using an effective or restructured external field. The derivation starts from the exact Yvon-Born-Green hierarchy and shows that the approximation can be very accurate when the interactions averaged over are slowly varying at characteristic nearest-neighbor distances. Application of LMF theory to Coulomb interactions alone allows for great simplifications of the governing equations. LMF theory then reduces to a single equation for a restructured electrostatic potential that satisfies Poisson's equation defined with a smoothed charge density. Because of this charge smoothing by a Gaussian of width sigma, this equation may be solved more simply than the detailed simulation geometry might suggest. Proper choice of the smoothing length sigma plays a major role in ensuring the accuracy of this approximation. We examine the results of a basic confinement of water between corrugated wall and justify the simple LMF equation used in a previous publication. We further generalize these results to confinements that include fixed charges in order to demonstrate the broader impact of charge smoothing by sigma. The slowly-varying part of the restructured electrostatic potential will be more symmetric than the local details of confinements.Comment: To be published in J Phys-Cond Matt; small misprint corrected in Eq. (12) in V

Chemical chronology of the Southern Coalsack

We demonstrate how the observed H2O ice column densities toward three dense globules in the Southern Coalsack could be used to constrain the ages of these sources. We derive ages of ~10^5 yr, in agreement with dynamical studies of these objects. We have modelled the chemical evolution of the globules, and show how the molecular abundances are controlled by both the gas density and the initial chemical conditions as the globules formed. Based on our derived ages, we predict the column densities of several species of interest. These predictions should be straightforward to test by performing molecular line observationsComment: 10 pages, 4 figures, in press at MNRA

Interplay of local hydrogen-bonding and long-ranged dipolar forces in simulations of confined water

Spherical truncations of Coulomb interactions in standard models for water permit efficient molecular simulations and can give remarkably accurate results for the structure of the uniform liquid. However truncations are known to produce significant errors in nonuniform systems, particularly for electrostatic properties. Local molecular field (LMF) theory corrects such truncations by use of an effective or restructured electrostatic potential that accounts for effects of the remaining long-ranged interactions through a density-weighted mean field average and satisfies a modified Poisson's equation defined with a Gaussian-smoothed charge density. We apply LMF theory to three simple molecular systems that exhibit different aspects of the failure of a naive application of spherical truncations -- water confined between hydrophobic walls, water confined between atomically-corrugated hydrophilic walls, and water confined between hydrophobic walls with an applied electric field. Spherical truncations of 1/r fail spectacularly for the final system in particular, and LMF theory corrects the failings for all three. Further, LMF theory provides a more intuitive way to understand the balance between local hydrogen bonding and longer-ranged electrostatics in molecular simulations involving water.Comment: Submitted to PNA

Attraction Between Like-Charged Walls: Short-Ranged Simulations Using Local Molecular Field Theory

Effective attraction between like-charged walls mediated by counterions is studied using local molecular field (LMF) theory. Monte Carlo simulations of the "mimic system'' given by LMF theory, with short-ranged "Coulomb core" interactions in an effective single particle potential incorporating a mean-field average of the long-ranged Coulomb interactions, provide a direct test of the theory, and are in excellent agreement with more complex simulations of the full Coulomb system by Moreira and Netz [Eur. Phys. J. E 8, 33 (2002)]. A simple, generally-applicable criterion to determine the consistency parameter sigma_{min} needed for accurate use of the LMF theory is presented