Vapor-liquid equilibrium and thermodynamic properties of saturated argon and krypton from Monte Carlo simulations using ab initio potentials.

Vapor-liquid equilibria and thermodynamic properties of saturated argon and krypton were calculated by semi-classical Monte Carlo simulations with the NpT + test particle method using ab initio potentials for the two-body and nonadditive three-body interactions. The NpT + test particle method was extended to the calculation of second-order thermodynamic properties, such as the isochoric and isobaric heat capacities or the speed of sound, of the saturated liquid and vapor by using our recently developed approach for the systematic calculation of arbitrary thermodynamic properties in the isothermal-isobaric ensemble. Generally, the results for all simulated properties agree well with experimental data and the current reference equations of state for argon and krypton. In particular, the results for the vapor pressure and for the density and speed of sound of the saturated liquid and vapor agree with the most accurate experimental data for both noble gases almost within the uncertainty of these data, a level of agreement unprecedented for many-particle simulations. This study demonstrates that the vapor-liquid equilibrium and thermodynamic properties at saturation of a pure fluid can be predicted by Monte Carlo simulations with high accuracy when the intermolecular interactions are described by state-of-the-art ab initio pair and nonadditive three-body potentials and quantum effects are accounted for.

The Chlamydia effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35.

The obligate intracellular bacterium Chlamydia trachomatis inserts a family of inclusion membrane (Inc) proteins into the membrane of its vacuole (the inclusion). The Inc CpoS is a critical suppressor of host cellular immune surveillance, but the underlying mechanism remained elusive. By complementing a cpoS mutant with various natural orthologs and variants of CpoS, we linked distinct molecular interactions of CpoS to distinct functions. Unexpectedly, we found CpoS to be essential for the formation of inclusion membrane microdomains that control the spatial organization of multiple Incs involved in signaling and modulation of the host cellular cytoskeleton. While the function of CpoS in microdomains was uncoupled from its role in the suppression of host cellular defenses, we found the ability of CpoS to interact with Rab GTPases to be required not only for the manipulation of membrane trafficking, such as to mediate transport of ceramide-derived lipids (sphingolipids) to the inclusion, but also for the inhibition of Stimulator of interferon genes (STING)-dependent type I interferon responses. Indeed, depletion of Rab35 phenocopied the exacerbated interferon responses observed during infection with CpoS-deficient mutants. Overall, our findings highlight the role of Inc-Inc interactions in shaping the inclusion microenvironment and the modulation of membrane trafficking as a pathogenic immune evasion strategy. IMPORTANCE Chlamydia trachomatis is a prevalent bacterial pathogen that causes blinding ocular scarring and urogenital infections that can lead to infertility and pregnancy complications. Because Chlamydia can only grow within its host cell, boosting the intrinsic defenses of human cells may represent a novel strategy to fight pathogen replication and survival. Hence, CpoS, a Chlamydia protein known to block host cellular defenses, or processes regulated by CpoS, could provide new opportunities for therapeutic intervention. By revealing CpoS as a multifunctional virulence factor and by linking its ability to block host cellular immune signaling to the modulation of membrane trafficking, the present work may provide a foundation for such rationale targeting and advances our understanding of how intracellular bacteria can shape and protect their growth niche.

Classical statistical mechanics in the µVL and µpR ensembles.

Molecular expressions for thermodynamic properties and derivatives of the entropy up to third order in the adiabatic grand-isochoric µVL and adiabatic grand-isobaric µpR ensembles are systematically derived using the methodology developed by Lustig for the microcanonical and canonical ensembles [J. Chem. Phys. 100, 3048 (1994)10.1063/1.466446; Mol. Phys. 110, 3041 (2012)10.1080/00268976.2012.695032]. They are expressed by phase-space functions, which represent derivatives of the entropy with respect to the chemical potential, the volume, and the Hill energy L in the µVL ensemble and with respect to the chemical potential, the pressure, and the Ray energy R in the µpR ensemble. The derived expressions are validated for both ensembles by Monte Carlo simulations for the simple Lennard-Jones model fluid at three selected state points.

Thermodynamic properties of krypton from Monte Carlo simulations using ab initio potentials.

Ten different thermodynamic properties of the noble gas krypton were calculated by Monte Carlo simulations in the isothermal-isobaric ensemble using a highly accurate ab initio pair potential, Feynman-Hibbs corrections for quantum effects, and an extended Axilrod-Teller-Muto potential to account for nonadditive three-body interactions. Fourteen state points at a liquid and a supercritical isotherm were simulated. To obtain results representative for macroscopic systems, simulations with several particle numbers were carried out and extrapolated to the thermodynamic limit. Our results agree well with experimental data from the literature, an accurate equation of state for krypton, and a recent virial equation of state (VEOS) for krypton in the region where the VEOS has converged. These results demonstrate that very good agreement between simulation and experiment can only be achieved if nonadditive three-body interactions and quantum effects are taken into account.

Thermodynamic properties of argon from Monte Carlo simulations using ab initio potentials.

Ten different thermodynamic properties of the noble gas argon in the liquid and supercritical regions were obtained from semiclassical Monte Carlo simulations in the isothermal-isobaric ensemble using ab initio potentials for the two-body and nonadditive three-body interactions. Our results for the density and speed of sound agree with the most accurate experimental data for argon almost within the uncertainty of these data, a level of agreement unprecedented for many-particle simulations. This demonstrates the high predictive but yet unexploited power of ab initio potentials in the field of molecular modeling and simulation for thermodynamic properties of fluids.

Effects of crystalline anisotropy on resonant acoustic loss of torsional quartz viscometers.

Vibrational modes of unrestrained elastic cylinders of trigonal crystals are studied using Ritz-based polynomial approximations for displacements formulated in rectangular Cartesian coordinates. The selected orientation of the threefold trigonal axis is perpendicular to the cylinder axis, corresponding to the configuration employed in torsional quartz viscometry (TQV) for characterizing Newtonian fluids. A revised working equation for TQV is derived, incorporating effects of crystalline anisotropy, and Ritz results are used to numerically quantify effects of acoustic radiation from surface-normal displacements and viscous loss from nontorsional surface-parallel displacements of resonant modes corresponding to the purely torsional modes of isotropic cylinders traditionally employed as an approximation in TQV analysis. For a cylinder typical of TQV, with 3 mm diameter and 50 mm length, the anisotropy-related correction to the extracted fluid viscosity is a positive shift of 36 ppm relative to the isotropic approximation, if radiative losses are neglected. This contribution is independent of fluid properties. Radiative losses depend on the properties of the fluid and reduce the extracted viscosity. The total magnitude of corrections varies between several tens of parts per million for low density gases to values on the order of 0.01% for normal liquids near atmospheric pressure and 0.06% for superfluid helium.

Rigorous expressions for thermodynamic properties in the NpH ensemble.

Molecular expressions for thermodynamic properties of fluids and derivatives of the entropy up to third order in the isoenthalpic-isobaric ensemble are derived by using the methodology developed by Lustig for the microcanonical and canonical ensembles [J. Chem. Phys. 100, 3048 (1994)JCPSA60021-960610.1063/1.466446; Mol. Phys. 110, 3041 (2012)MOPHAM0026-897610.1080/00268976.2012.695032]. They are expressed in a systematic way by phase-space functions, which represent derivatives of the phase-space volume with respect to enthalpy and pressure. The expressions for thermodynamic properties contain only ensemble averages of combinations of the kinetic energy and volume of the system. Thus, the calculation of thermodynamic properties in the isoenthalpic-isobaric ensemble does not require volume derivatives of the potential energy. This is particularly advantageous in Monte Carlo simulations when the interactions between molecules are described by very accurate ab initio pair and nonadditive three-body potentials. The derived expressions are validated by Monte Carlo simulations for the simple Lennard-Jones model fluid as a test case.

Classical statistical mechanics in the grand canonical ensemble.

The methodology developed by Lustig for calculating thermodynamic properties in the microcanonical and canonical ensembles [J. Chem. Phys. 100, 3048 (1994)JCPSA60021-960610.1063/1.466446; Mol. Phys. 110, 3041 (2012)MOPHAM0026-897610.1080/00268976.2012.695032] is applied to derive rigorous expressions for thermodynamic properties of fluids in the grand canonical ensemble. All properties are expressed by phase-space functions, which are related to derivatives of the grand canonical potential with respect to the three independent variables of the ensemble: temperature, volume, and chemical potential. The phase-space functions contain ensemble averages of combinations of the number of particles, potential energy, and derivatives of the potential energy with respect to volume. In addition, expressions for the phase-space functions for temperature-dependent potentials are provided, which are required to account for quantum corrections semiclassically in classical simulations. Using the Lennard-Jones model fluid as a test case, the derived expressions are validated by Monte Carlo simulations. In contrast to expressions for the thermal expansion coefficient, the isothermal compressibility, and the thermal pressure coefficient from the literature, our expressions yield more reliable results for these properties, which agree well with a recent accurate equation of state for the Lennard-Jones model fluid. Moreover, they become equivalent to the corresponding expressions in the canonical ensemble in the thermodynamic limit.

Systematic formulation of thermodynamic properties in the NpT ensemble.

Molecular expressions for thermodynamic properties and derivatives of the Gibbs energy up to third order in the isobaric-isothermal (NpT) ensemble are systematically derived using the methodology developed by Lustig for the microcanonical and canonical ensembles [J. Chem. Phys. 100, 3048 (1994)10.1063/1.466446; Mol. Phys. 110, 3041 (2012)10.1080/00268976.2012.695032]. They are expressed by phase-space functions, which represent derivatives of the Gibbs energy with respect to temperature and pressure. Additionally, expressions for the phase-space functions for temperature-dependent potentials are provided, which, for example, are required when quantum corrections, e.g., Feynman-Hibbs corrections, are applied in classical simulations. The derived expressions are validated by Monte Carlo simulations for the simple Lennard-Jones model fluid at three selected state points. A unique result is that the phase-space functions contain only ensemble averages of combinations of powers of enthalpy and volume. Thus, the calculation of thermodynamic properties in the NpT ensemble does not require volume derivatives of the potential energy. This is particularly advantageous in Monte Carlo simulations when the interactions between molecules are described by empirical force fields or very accurate ab initio pair and nonadditive three-body potentials.

Eighth-order virial equation of state and speed-of-sound measurements for krypton.

An eighth-order virial equation of state (VEOS) for krypton, valid for temperatures up to 5000 K, was developed using the accurate potential functions proposed by Jäger et al. [J. Chem. Phys. 144, 114304 (2016)] for the pair interactions and nonadditive three-body interactions between krypton atoms. While the second and third virial coefficients were already calculated by Jäger et al., the fourth- to eighth-order coefficients were determined in the present work. A simple analytical function was fitted individually to the calculated values of each virial coefficient to obtain the VEOS in an easy-to-use analytical form. To enable a stringent test of the quality of the new VEOS, we measured the speed of sound in krypton in the temperature range from 200 K to 420 K and at pressures up to 100 MPa with a very low uncertainty (at the 0.95 confidence level) of 0.005%-0.018% employing the pulse-echo technique. In order to verify that the isotopic composition of the krypton sample conforms to that of natural krypton in air, high-precision measurements of krypton isotope ratios using a high-sensitivity noble gas mass spectrometer were performed. The extensive comparison with the new speed-of-sound data as well as with experimental p-ρ-T and speed-of-sound data from the literature indicates that pressures and speeds of sound calculated using our new VEOS have uncertainties (at the 0.95 confidence level) of less than 0.1% at state points at which the VEOS is sufficiently converged.

Wide-ranging Absolute Viscosity Measurements of Sub- and Supercritical 1,1,1-trifluoroethane (R143a).

The viscosity of 1,1,1-trifluoroethane (R143a) was measured with a piezoelectrically actuated, torsionally vibrating quartz sensor. The measurements extended over a temperature range from 300 K to 440 K with pressures to 68 MPa and covered states from the dilute gas to the compressed liquid. The influence of the drive voltage on the torsional displacement of the vibrator in fluid and in vacuum was systematically investigated. Since R143a is highly polar, the sample conductance and susceptance were also monitored with the sensor to detect possible electroviscous contributions in the measured viscosities. None were identified so that the estimated uncertainty of the measurements remains at 2 % at a 95 % confidence level (coverage factor k = 2). The results agree well within this margin with literature data that were determined with four other viscometric techniques.

Differentiation and Functionality of Bone Marrow-Derived Mast Cells Depend on Varying Physiologic Oxygen Conditions.

Mast cells (MCs) are long-living multifunctional innate immune cells that originate from hematopoietic precursors and specifically differentiate in the destination tissue, e.g., skin, respiratory mucosa, intestine, where they mediate immune cell recruitment and antimicrobial defense. In vivo these tissues have characteristic physiological oxygen levels that are considerably lower than the atmospheric oxygen conditions (159 mmHg, 21% O2; 5% CO2) traditionally used to differentiate MCs and to study their functionality in vitro. Only little is known about the impact of physiological oxygen conditions on the differentiation process of MCs. This study aimed to characterize the differentiation of immature murine bone marrow-derived MCs under physioxia in vitro (7% O2; 53 mmHg; 5% CO2). Bone marrow-derived suspension cells were differentiated in the presence of interleukin-3 with continuous, non-invasive determination of the oxygen level using a Fibox4-PSt3 measurement system without technique-caused oxygen consumption. Trypan blue staining confirmed cellular viability during the specified period. Interestingly, MCs cultivated at 7% O2 showed a significantly delayed differentiation rate defined by CD117-positive cells, analyzed by flow cytometry, and reached >95% CD117 positive population at day 32 after isolation. Importantly, MCs differentiated under physioxia displayed a decreased transcript expression level of hif-1α and selected target genes vegf, il-6, and tnf-α, but an increase of foxo3 and vhl expression compared to MCs cultivated under normoxia. Moreover, the production of reactive oxygen species as well as the amount of intracellular stored histamine was significantly lower in MCs differentiated under low oxygen levels, which might have consequences for their function such as immunomodulation of other immune cells. These results show for the first time that physioxia substantially affect maturation and the properties of MCs and highlight the need to study their function under physiologically relevant oxygen conditions.

Pressure derivatives in the classical molecular-dynamics ensemble.

The calculation of thermodynamic state variables, particularly derivatives of the pressure with respect to density and temperature, in conventional molecular-dynamics simulations is considered in the frame of the comprehensive treatment of the molecular-dynamics ensemble by Lustig [J. Chem. Phys. 100, 3048 (1994)]. This paper improves the work of Lustig in two aspects. In the first place, a general expression for the basic phase-space functions in the molecular-dynamics ensemble is derived, which takes into account that a mechanical quantity G is, in addition to the number of particles, the volume, the energy, and the total momentum of the system, a constant of motion. G is related to the initial position of the center of mass of the system. Secondly, the correct general expression for volume derivatives of the potential energy is derived. This latter result solves a problem reported by Lustig [J. Chem. Phys. 109, 8816 (1998)] and Meier [Computer Simulation and Interpretation of the Transport Coefficients of the Lennard-Jones Model Fluid (Shaker, Aachen, 2002)] and enables the correct calculation of the isentropic and isothermal compressibilities, the speed of sound, and, in principle, all higher pressure derivatives. The derived equations are verified by calculations of several state variables and pressure derivatives up to second order by molecular-dynamics simulations with 256 particles at two state points of the Lennard-Jones fluid in the gas and liquid regions. It is also found that it is impossible for systems of this size to calculate third- and higher-order pressure derivatives due to the limited accuracy of the algorithm employed to integrate the equations of motion.

Sphingoid base is required for translation initiation during heat stress in Saccharomyces cerevisiae.

Sphingolipids are required for many cellular functions including response to heat shock. We analyzed the yeast lcb1-100 mutant, which is conditionally impaired in the first step of sphingolipid biosynthesis and shows a strong decrease in heat shock protein synthesis and viability. Transcription and nuclear export of heat shock protein mRNAs is not affected. However, lcb1-100 cells exhibited a strong decrease in protein synthesis caused by a defect in translation initiation under heat stress conditions. The essential lipid is sphingoid base, not ceramide or sphingoid base phosphates. Deletion of the eIF4E-binding protein Eap1p in lcb-100 cells restored translation of heat shock proteins and increased viability. The translation defect during heat stress in lcb1-100 was due at least partially to a reduced function of the sphingoid base-activated PKH1/2 protein kinases. In addition, depletion of the translation initiation factor eIF4G was observed in lcb1-100 cells and ubiquitin overexpression allowed partial recovery of translation after heat stress. Taken together, we have shown a requirement for sphingoid bases during the recovery from heat shock and suggest that this reflects a direct lipid-dependent signal to the cap-dependent translation initiation apparatus.

Transport coefficients of the Lennard-Jones model fluid. III. Bulk viscosity.

In an extensive computer simulation study, the transport coefficients of the Lennard-Jones model fluid were determined with high accuracy from equilibrium molecular-dynamics simulations. In the frame of time-correlation function theory, the generalized Einstein relations were employed to evaluate the transport coefficients. This third of a series of four papers presents the results for the bulk viscosity. With comprehensive simulation data at over 350 state points, the temperature and density dependences of the bulk viscosity are characterized in this work over a wide range of fluid states. The bulk viscosity exhibits a large critical enhancement similar to that known for the thermal conductivity, but it extends much farther into the supercritical region and can be observed even at 4.5 times the critical temperature. An investigation of the pressure-fluctuation autocorrelation functions shows that the enhancement is caused by extremely slowly decaying pressure fluctuations.

Transport coefficients of the Lennard-Jones model fluid. II Self-diffusion.

In an extensive computer simulation study, the transport coefficients of the Lennard-Jones model fluid were determined with high accuracy from equilibrium molecular-dynamics simulations. In the frame of time-correlation function theory, the generalized Einstein relations were employed to evaluate the transport coefficients. This second of a series of four papers presents the results for the self-diffusion coefficient, and discusses and interprets the behavior of this transport coefficient in the fluid region of the phase diagram. The uncertainty of the self-diffusion data is estimated to be 1% in the gas region and 0.5% at high-density liquid states. With the very accurate data, even fine details in the shape of the self-diffusion isotherms are resolved, and the previously little-investigated behavior of the self-diffusion coefficient at low-density gaseous states is analyzed in detail. Finally, aspects of the mass transport mechanisms on the molecular scale are explored by an analysis of the velocity autocorrelation functions.

Transport coefficients of the Lennard-Jones model fluid. I. Viscosity.

In an extensive computer simulation study, the transport coefficients of the Lennard-Jones model fluid were determined with high accuracy from equilibrium molecular-dynamics simulations. In the frame of time-correlation function theory, the generalized Einstein relations were employed to evaluate the transport coefficients. This first of a series of four papers presents the results for the viscosity, and discusses and interprets the behavior of this transport coefficient in the fluid region of the phase diagram. Moreover, the kinetic-kinetic, kinetic-potential, and potential-potential viscosity contributions are resolved over the whole range of fluid states, and their characteristic dependence on temperature and density is described. Finally, an additional analysis of the shear-stress correlation functions reveals aspects of the momentum-transport mechanisms on the molecular scale.

Increased ubiquitin-dependent degradation can replace the essential requirement for heat shock protein induction.

Serine palmitoyltransferase, the first enzyme in ceramide biosynthesis, is required for resistance to heat shock. We show that increased heat shock sensitivity in the absence of serine palmitoyltransferase activity correlates with a lack of induction of the major heat shock proteins (Hsps) at high temperature. Normal heat shock resistance can be restored, without restoration of ceramide synthesis or induction of Hsps, by overexpression of ubiquitin. This function of ubiquitin requires the proteasome. These data imply that the essential function of Hsp induction is the removal of misfolded or aggregated proteins, not their refolding. This suggests that cells stressed by heat shock do not die because of the loss of protein activity due to their denaturation, but because of the inherent toxicity of the denatured and/or aggregated proteins.