Multimodal [18 F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice.

In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([18 F]FDG) and [18 F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [18 F]FDG, for detecting inflammatory processes, or [18 F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUVmean ) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [18 F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [18 F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [18 F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Hypercooling Temperature of Water is about 100 K Higher than Calculated before.

For deeply supercooled liquids the transition from a two-stage freezing process to complete solidification in just one freezing step occurs at the hypercooling temperature, a term that seems to be almost unknown in water research; to our knowledge, it has only been mentioned by Dolan et al. for high-pressure ice. The reason for the absence of this expression may be that the best estimate to be found in the literature for the hypercooling temperature of water is about -160 °C (113 K). This temperature is far below the limit of experimentally realizable degrees of supercooling near -40 °C (233 K), which marks the homogeneous nucleation temperature TH of common pure water; in fact, it is even below the glass-transition temperature (133 K). Here we show that, surprisingly, a more thorough analysis taking into account the temperature dependence of the heat capacities of water and ice as well as of the enthalpy of freezing shows that the hypercooling temperature of water is about -64 °C or 209 K, almost 100 K higher than estimated before. One of the most exciting consequences is that existing experiments are already able to reach these degrees of supercooling, and it is our prediction that a transition in the freezing behavior occurs at these temperatures.

A corresponding-states analysis of the liquid-vapor equilibrium properties of common water models.

Many atomistic potential models have been proposed to reproduce the properties of real water and to capture as many of its anomalies as possible. The large number of different models indicates that this task is by no means an easy one. Some models are reasonably successful for various properties, while others are designed to account for only a very few specific features of water accurately. Among the most popular models are SPC/E, TIP4P, TIP4P/2005, TIP4P/Ice, and TIP5P-E. Here, we report the equilibrium properties of the liquid-vapor coexistence, such as the densities of the liquid phase and the vapor phase, the interfacial tension between them, and the vapor pressure at saturation. From these data, the critical parameters are determined and subsequently used to cast the liquid-vapor coexistence properties into a corresponding-states form following Guggenheim's suggestions. Doing so reveals that the three TIP4P-based models display the same corresponding-states behavior and that the SPC/E model behaves quite similarly. Only the TIP5P-E model shows clear deviations from the corresponding-states properties of the other models. A comparison with data for real water shows that the reduced surface tension is well described, while the reduced coexistence curve is too wide. The models underestimate the critical compressibility factor and overestimate Guggenheim's ratio as well as the reduced boiling temperature (Guldberg's ratio). As demonstrated by the collapse of the data for the TIP4P-based models, these deviations are inherent to the specific model and cannot be corrected by a simple reparametrization. For comparison, the results for two recent polarizable models, HBP and BK3, are shown, and both models are seen to perform well in terms of absolute numbers and in a corresponding-states framework. The kind of analysis applied here can therefore be used as a guideline in the design of more accurate and yet simple multi-purpose models of water.

Corresponding-states behavior of SPC/E-based modified (bent and hybrid) water models.

The remarkable and sometimes anomalous properties of water can be traced back at the molecular level to the tetrahedral coordination of molecules due to the ability of a water molecule to form four hydrogen bonds to its neighbors; this feature allows for the formation of a network that greatly influences the thermodynamic behavior. Computer simulations are becoming increasingly important for our understanding of water. Molecular models of water, such as SPC/E, are needed for this purpose, and they have proved to capture many important features of real water. Modifications of the SPC/E model have been proposed, some changing the H-O-H angle (bent models) and others increasing the importance of dispersion interactions (hybrid models), to study the structural features that set water apart from other polar fluids and from simple fluids such as argon. Here, we focus on the properties at liquid-vapor equilibrium and study the coexistence curve, the interfacial tension, and the vapor pressure in a corresponding-states approach. In particular, we calculate Guggenheim's ratio for the reduced apparent enthalpy of vaporization and Guldberg's ratio for the reduced normal boiling point. This analysis offers additional insight from a more macroscopic, thermodynamic perspective and augments that which has already been learned at the molecular level from simulations. In the hybrid models, the relative importance of dispersion interactions is increased, which turns the modified water into a Lennard-Jones-like fluid. Consequently, in a corresponding-states framework, the typical behavior of simple fluids, such as argon, is seen to be approached asymptotically. For the bent models, decreasing the bond angle turns the model essentially into a polar diatomic fluid in which the particles form linear molecular arrangements; as a consequence, characteristic features of the corresponding-states behavior of hydrogen halides emerge.

Corresponding-states behavior of an ionic model fluid with variable dispersion interactions.

Guggenheim's corresponding-states approach for simple fluids leads to a remarkably universal representation of their thermophysical properties. For more complex fluids, such as polar or ionic ones, deviations from this type of behavior are to be expected, thereby supplying us with valuable information about the thermodynamic consequences of the interaction details in fluids. Here, the gradual transition of a simple fluid to an ionic one is studied by varying the relative strength of the dispersion interactions compared to the electrostatic interactions among the charged particles. In addition to the effects on the reduced surface tension that were reported earlier [F. Leroy and V. C. Weiss, J. Chem. Phys. 134, 094703 (2011)], we address the shape of the coexistence curve and focus on properties that are related to and derived from the vapor pressure. These quantities include the enthalpy and entropy of vaporization, the boiling point, and the critical compressibility factor Zc. For all of these properties, the crossover from simple to characteristically ionic fluid is seen once the dispersive attraction drops below 20%-40% of the electrostatic attraction (as measured for two particles at contact). Below this threshold, ionic fluids display characteristically low values of Zc as well as large Guggenheim and Guldberg ratios for the reduced enthalpy of vaporization and the reduced boiling point, respectively. The coexistence curves are wider and more skewed than those for simple fluids. The results for the ionic model fluid with variable dispersion interactions improve our understanding of the behavior of real ionic fluids, such as inorganic molten salts and room temperature ionic liquids, by gauging the importance of different types of interactions for thermodynamic properties.

Corresponding-states behavior of a dipolar model fluid with variable dispersion interactions and its relevance to the anomalies of hydrogen fluoride.

More than two decades ago, the elusiveness of a liquid-vapor equilibrium and a corresponding critical point in simulations of the supposedly simple model of dipolar hard spheres came as a surprise to many liquid matter theorists. van Leeuwen and Smit [Phys. Rev. Lett. 71, 3991 (1993)] showed that a minimum of attractive dispersion interactions among the dipolar particles may be needed to observe regular fluid behavior. Here, we adopt their approach and use an only slightly modified model, in which the original point dipole is replaced by a dipole moment produced by charges that are separated in space, to study the influence of dispersion interactions of variable strength on the coexistence and interfacial properties of a polar fluid. The thermophysical properties are discussed in terms of Guggenheim's corresponding-states approach. In this way, the coexistence curve, the critical compressibility factor, the surface tension, Guggenheim's ratio, and modifications of Guldberg's and Trouton's rules (related to the vapor pressure and the enthalpy of vaporization) are analyzed. As the importance of dispersion is decreased, a crossover from simple-fluid behavior to that characteristic of strongly dipolar systems takes place; for some properties, this transition is monotonic, but for others it occurs non-monotonically. For strongly dipolar systems, the reduced surface tension is very low, whereas Guggenheim's ratio and Guldberg's ratio are found to be high. The critical compressibility factor is smaller, and the coexistence curve is wider and more skewed than for simple fluids. For very weak dispersion, liquid-vapor equilibrium is still observable, but the interfacial tension is extremely low and may, eventually, vanish marking the end of the existence of a liquid phase. We discuss the implications of our findings for real fluids, in particular, for hydrogen fluoride.

Predicting critical temperatures of ionic and non-ionic fluids from thermophysical data obtained near the melting point.

In the correlation and prediction of thermophysical data of fluids based on a corresponding-states approach, the critical temperature Tc plays a central role. For some fluids, in particular ionic ones, however, the critical region is difficult or even impossible to access experimentally. For molten salts, Tc is on the order of 3000 K, which makes accurate measurements a challenging task. Room temperature ionic liquids (RTILs) decompose thermally between 400 K and 600 K due to their organic constituents; this range of temperatures is hundreds of degrees below recent estimates of their Tc. In both cases, reliable methods to deduce Tc based on extrapolations of experimental data recorded at much lower temperatures near the triple or melting points are needed and useful because the critical point influences the fluid's behavior in the entire liquid region. Here, we propose to employ the scaling approach leading to universal fluid behavior [Román et al., J. Chem. Phys. 123, 124512 (2005)] to derive a very simple expression that allows one to estimate Tc from the density of the liquid, the surface tension, or the enthalpy of vaporization measured in a very narrow range of low temperatures. We demonstrate the validity of the approach for simple and polar neutral fluids, for which Tc is known, and then use the methodology to obtain estimates of Tc for ionic fluids. When comparing these estimates to those reported in the literature, good agreement is found for RTILs, whereas the ones for the molten salts NaCl and KCl are lower than previous estimates by 10%. The coexistence curve for ionic fluids is found to be more adequately described by an effective exponent of ßeff = 0.5 than by ßeff = 0.33.

Kinetic aspects of the thermostatted growth of ice from supercooled water in simulations.

In experiments, the growth rate of ice from supercooled water is seen to increase with the degree of supercooling, that is, the lower the temperature, the faster the crystallization takes place. In molecular dynamics simulations of the freezing process, however, the temperature is usually kept constant by means of a thermostat that artificially removes the heat released during the crystallization by scaling the velocities of the particles. This direct removal of energy from the system replaces a more realistic heat-conduction mechanism and is believed to be responsible for the curious observation that the thermostatted ice growth proceeds fastest near the melting point and more slowly at lower temperatures, which is exactly opposite to the experimental findings [M. A. Carignano, P. B. Shepson, and I. Szleifer, Mol. Phys. 103, 2957 (2005)]. This trend is explained by the diffusion and the reorientation of molecules in the liquid becoming the rate-determining steps for the crystal growth, both of which are slower at low temperatures. Yet, for a different set of simulations, a kinetic behavior analogous to the experimental finding has been reported [H. Nada and Y. Furukawa, J. Crystal Growth 283, 242 (2005)]. To clarify this apparent contradiction, we perform relatively long simulations of the TIP4P/Ice model in an extended range of temperatures. The temperature dependence of the thermostatted ice growth is seen to be more complex than was previously reported: The crystallization process is very slow close to the melting point at 270 K, where the thermodynamic driving force for the phase transition is weak. On lowering the temperature, the growth rate initially increases, but displays a maximum near 260 K. At even lower temperatures, the freezing process slows down again due to the reduced diffusivity in the liquid. The velocity of the thermostatted melting process, in contrast, shows a monotonic increase upon raising the temperature beyond the normal melting point. In this case, the effects of the increasing thermodynamic driving force and the faster diffusion at higher temperatures reinforce each other. In the context of this study, we also report data for the diffusion coefficient as a function of temperature for the water models TIP4P/Ice and TIP4P/2005.

What makes ionic fluids characteristically ionic? A corresponding-states analysis of the surface tension of an ionic model fluid with variable dispersion interactions.

Inorganic molten salts, such as NaCl, are known to show characteristically lower values of Guggenheim's corresponding-states surface tension γ(red) at a given reduced temperature T∕T(c) than simple or aprotic polar fluids. Recently, the corresponding values of γ(red) for (some) room temperature ionic liquids (RTILs) were found in the same region as those for weakly polar fluids, that is, markedly above the values typical of inorganic molten salts despite the ionic character of RTILs. Here, we present the results of simulations of an ionic model fluid in which the strength of attractive dispersion interactions among the ions is varied relative to the Coulomb interactions. For weak dispersive interactions, the behavior known for real inorganic molten salts is found. If the attractive dispersion energy of two unlike ions at contact exceeds 20% of the Coulombic attraction in such an isolated ion pair, γ(red) increases markedly and approaches the region of values for simple and polar fluids. Rough theoretical estimates of the relative strengths of dispersive and Coulombic attractions in molten inorganic salts and in RTILs support our conclusion that the dispersion interactions in RTILs are strong enough for their corresponding-states surface tension to behave regularly and, thus, to deviate from the values one would expect for strongly ionic systems.

Guggenheim's rule and the enthalpy of vaporization of simple and polar fluids, molten salts, and room temperature ionic liquids.

One of Guggenheim's many corresponding-states rules for simple fluids implies that the molar enthalpy of vaporization (determined at the temperature at which the pressure reaches 1/50th of its critical value, which approximately coincides with the normal boiling point) divided by the critical temperature has a value of roughly 5.2R, where R is the universal gas constant. For more complex fluids, such as strongly polar and ionic fluids, one must expect deviations from Guggenheim's rule. Such a deviation has far-reaching consequences for other empirical rules related to the vaporization of fluids, namely Guldberg's rule and Trouton's rule. We evaluate these characteristic quantities for simple fluids, polar fluids, hydrogen-bonding fluids, simple inorganic molten salts, and room temperature ionic liquids (RTILs). For the ionic fluids, the critical parameters are not accessible to direct experimental observation; therefore, suitable extrapolation schemes have to be applied. For the RTILs [1-n-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imides, where the alkyl chain is ethyl, butyl, hexyl, or octyl], the critical temperature is estimated by extrapolating the surface tension to zero using Guggenheim's and Eotvos' rules; the critical density is obtained using the linear-diameter rule. It is shown that the RTILs adhere to Guggenheim's master curve for the reduced surface tension of simple and moderately polar fluids, but that they deviate significantly from his rule for the reduced enthalpy of vaporization of simple fluids. Consequences for evaluating the Trouton constant of RTILs, the value of which has been discussed controversially in the literature, are indicated.

Vibrational circular dichroism of 3-(trifluoroacetyl)-camphor and its interaction with chiral amines.

Vibrational circular dichroism (VCD) spectroscopy and density functional theory (DFT) calculations are used to investigate the keto-enol equilibrium of 3-(trifluoroacetyl)-camphor (TFC) and to study the interaction of TFC with chiral amines in deuterated Chloroform. It is shown that the VCD spectra of the enol- and keto forms of TFC can clearly be distinguished and that the enol form is favored. By deprotonation of the TFC enol with chiral amines, no indication of a mutual diasteriomeric influence on the VCD spectra induced by transfer of stereochemical information between the chiral ionic species is found, neither experimentally nor theoretically.

Effective exponents in the long-range critical wetting of alkanes on aqueous substrates.

Alkanes on water show a two-stage wetting transition. Upon raising the temperature, a first-order transition from a molecularly thin to a mesoscopically thick liquid film is followed by a continuous divergence of the film thickness. This second transition is brought about by long-range interactions between adsorbate and substrate and is, therefore, referred to as long-range critical wetting. The divergence of the film thickness is theoretically expected to occur according to the asymptotic power law l approximately (Tw,c-T)betas, with betas=-1. This value has indeed been found for pentane on pure water; however, for hexane on salt solutions of different concentrations, betas=-0.73 was found for a 1.5M solution of NaCl and betas=-0.57 for a 2.5M salt solution. In addition, for hexane on a 2.5M solution of NaCl, an exponent of alphas=0.1 was found from contact-angle measurements, differing greatly from the theoretically expected value of alphas=-1. Using Dzyaloshinskii-Lifshitz-Pitaevskii theory, we calculate effective local exponents in order to explain the experimental findings. Taking into account the uncertainty of the exponents derived from experiments as well as the temperature range in which the measurements were carried out, a reasonable agreement between theory and experiment is found, thereby providing a consistent approach to resolving the apparently anomalous behavior of hexane on brine. The experimentally observed exponents betas=-0.57 and alphas=0.1 are also compatible with a long-range tricritical wetting transition, which is characterized by betas=-1/2 and alphas=0; this alternative explanation of the experimental findings is neither supported nor completely ruled out by our calculations.

Theoretical description of the adsorption and the wetting behavior of alkanes on water.

The wetting behavior of alkanes of medium chain length (e.g., pentane, hexane, and heptane) on water is more complex than the usually observed first-order wetting transition from partial to complete wetting by showing a sequence of two transitions. In this sequential-wetting scenario, a first-order transition from a microscopically thin to a mesoscopically thick layer of liquid on the substrate surface is followed by a continuous divergence of the film thickness upon increase of the temperature. This critical transition to complete wetting at T(w,c) is solely determined by long-range interactions between substrate and adsorbate, which are well-described by Dzyaloshinskii-Lifshitz-Pitaevskii [Adv. Phys. 10, 165 (1961)] theory in terms of the static dielectric constants and the refractive indices of the media involved. The first-order thin-thick transition, however, which occurs at a lower temperature T(w,1), results from an interplay of short-range and long-range forces and is notoriously more difficult to describe because a satisfactory theory of the short-range interactions between substrate and adsorbate is still missing. The approach presented in this paper attempts to account for the short-range interactions in an effective way: Within a Cahn-type [J. Chem. Phys. 66, 3667 (1977)] theory that has been augmented for long-range interactions and modified to treat the first layer of adsorbed molecules in a lattice-gas approach, the contact energy is deduced from the surface pressure, which in turn is calculated using a two-dimensional van der Waals equation of state and an expression for the Henry's law constant that was derived by Hirasaki [J. Adhes. Sci. Technol. 7, 285 (1993)]. The method uses only the dielectric properties of the isolated bulk media and simple assumptions on the size and the shape of the adsorbed alkane molecules and leads to satisfactory results for the transition temperatures T(w,1) and T(w,c).

Anomalous corresponding-states surface tension of hydrogen fluoride and of the Onsager model.

In a corresponding-states analysis of the liquid-vapor surface tension originally suggested by Guggenheim, we study the behavior of different simple (i.e., nonpolar), polar and ionic fluids. The results are compared to the corresponding ones for model fluids of each of the three types. For simple and weakly polar fluids (both real and model), the data map onto a master curve, as demonstrated by Guggenheim. For strongly dipolar, associating fluids, which also exhibit hydrogen bonding, one finds deviations from the master curve at low temperatures and, thus, observes the characteristic sigmoid behavior of the reduced surface tension as a function of temperature. The same is obtained for the model ionic fluid, the restricted primitive model. Truly exceptionally low values of the reduced surface tension are found for hydrogen fluoride and for the Onsager model of dipolar fluids, the surface tension of which we evaluate using an approximate hypernetted chain relation to obtain the square-gradient term in a modified van der Waals theory. Remarkably, in the corresponding-states plot, the surface tensions of HF and of the Onsager model agree very closely, while being well separated from the values for the other fluids. We also study the gradual transition of a model fluid from a simple fluid to a strongly dipolar one by varying the relative strength of dipolar and dispersion forces.

Liquid-vapor interface of square-well fluids of variable interaction range.

Properties of the liquid-vapor interface of square-well fluids with ranges of interaction lambda=1.5, 2.0, and 3.0 are obtained by Monte Carlo simulations and from square-gradient theories that combine the Carnahan-Starling equation of state for hard spheres with the second and third virial coefficients. The predicted surface tensions show good agreement with the simulation results for lambda=2 and for lambda=3 in a temperature range reasonably close to the critical point, 0.8

Long-range critical wetting: observation of a critical end point.

Alkanes deposited on aqueous substrates exhibit two different types of wetting behavior: alternatively to the usual first-order wetting transition, a sequential-wetting scenario of a long-range critical wetting transition preceded by a first-order thin-thick transition may be observed. Here, we present the first successful experimental attempt to locate the transition point between the standard first-order wetting and the long-range critical wetting: a critical end point, observed in a mixture of pentane and hexane which is deposited on an aqueous solution of glucose. Furthermore, we present the first direct measurement of the contact angle in the intermediate wetting state (frustrated-complete wetting) in the sequential-wetting scenario of hexane on brine and compare to theoretical predictions.