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The many-body polarization energy is the major source of nonadditivity in strongly polar systems such as water. This nonadditivity is often considerable and must be included, if only in an average manner, to correctly describe the physical properties of the system. Models for the polarization energy are usually parametrized using experimental data, or theoretical estimates of the many-body effects. Here we show how many-body polarization models can be developed for water complexes using data for the monomer and dimer only using ideas recently developed in the field of intermolecular perturbation theory and state-of-the-art approaches for calculating distributed molecular properties based on the iterated stockholder atoms (ISA) algorithm. We show how these models can be calculated, and we validate their accuracy in describing the many-body nonadditive energies of a range of water clusters. We further investigate their sensitivity to the details of the polarization damping models used. We show how our very best polarization models yield many-body energies that agree with those computed with coupled-cluster methods, but at a fraction of the computational cost.

The possible structures of (CdSe)nand (CdS)n(nup to 34) nanoclusters were systematically studied using the ab initio random structure searching (AIRSS) method. We have been able to find stable, symmetric nanoclusters not previously discovered; using the computed pair distribution functions, we have put forward a hypothesis for the increased stability of these clusters. We have also been able to investigate structural features of the transformation to the bulk: for (CdS)nwith n< 16 and (CdSe)nwith n< 21, structures based on rings and cages with coordination number up to 3 are favored, while for larger n, the minimum-energy structures are more bulklike with an average coordination number larger than 3. This indicates a gradual transformation from a cagelike structure to a bulklike structure as the number of atoms increases. One striking finding was that for any value of n, the range of structures formed a continuous distribution of cluster energies rather than there being significant energy differences between them. This work created an extensive database of benchmarks and candidate structures for these systems.

Accurately describing long-range interactions is a significant challenge in molecular dynamics (MD) simulations of proteins. High-quality long-range potential is also an important component of the range-separated machine learning force field. This study introduces a comprehensive asymptotic parameter database encompassing atomic multipole moments, polarizabilities, and dispersion coefficients. Leveraging active learning, our database comprehensively represents protein fragments with up to 8 heavy atoms, capturing their conformational diversity with merely 78,000 data points. Additionally, the E(3) neural network (E3NN) is employed to predict the asymptotic parameters directly from the local geometry. The E3NN models demonstrate exceptional accuracy and transferability across all asymptotic parameters, achieving an R2of 0.999 for both protein fragments and 20 amino acid dipeptide test sets. The long-range electrostatic and dispersion energies can be obtained using the E3NN-predicted parameters, with an error of 0.07 and 0.02 kcal/mol, respectively, when compared to symmetry-adapted perturbation theory (SAPT). Therefore, our force fields demonstrate the capability to accurately describe long-range interactions in proteins, paving the way for next-generation protein force fields.

Nearly all standard force fields employ the “sum-of-spheres” approximation, which models intermolecular interactions purely in terms of interatomic distances. Nonetheless, atoms in molecules can have significantly nonspherical shapes, leading to interatomic interaction energies with strong orientation dependencies. Neglecting this “atomic-level anisotropy” can lead to significant errors in predicting interaction energies. Herein, we propose a simple, transferable, and computationally efficient model (MASTIFF) whereby atomic-level orientation dependence can be incorporated into ab initio intermolecular force fields. MASTIFF includes anisotropic exchange-repulsion, charge penetration, and dispersion effects, in conjunction with a standard treatment of anisotropic long-range (multipolar) electrostatics. To validate our approach, we benchmark MASTIFF against various sum-of-spheres models over a large library of intermolecular interactions between small organic molecules. MASTIFF achieves quantitative accuracy, with respect to both high-level electronic structure theory and experiment, thus showing promise as a basis for “next-generation” force field development.

Creating accurate, analytic atom–atom potentials for small organic molecules from first principles can be a time-consuming and computationally intensive task, particularly if we also require them to include explicit polarization terms, which are essential in many systems. We describe how the CamCASP suite of programs can be used to generate such potentials using some of the most accurate electronic structure methods currently applicable. We derive the long-range terms from monomer properties and determine the short-range anisotropy parameters by a novel and robust method based on the iterated stockholder atom approach. Using these techniques, we develop distributed multipole models for the electrostatic, polarization, and dispersion interactions in the pyridine dimer and develop a series of many-body potentials for the pyridine system. Even the simplest of these potentials exhibits root mean square errors of only about 0.6 kJ mol–1for the low-energy pyridine dimers, significantly surpassing the best empirical potentials. Our best model is shown to support eight stable minima, four of which have not been reported before in the literature. Further, the functional form can be made systematically more elaborate so as to improve the accuracy without a significant increase in the human-time spent in their generation. We investigate the effects of anisotropy, rank of multipoles, and choice of polarizability and dispersion models.

Short-range repulsion within intermolecular force fields is conventionally described by either Lennard-Jones (A/r12) or Born–Mayer (Aexp(−Br)) forms. Despite their widespread use, these simple functional forms are often unable to describe the interaction energy accurately over a broad range of intermolecular distances, thus creating challenges in the development of ab initio force fields and potentially leading to decreased accuracy and transferability. Herein, we derive a novel short-range functional form based on a simple Slater-like model of overlapping atomic densities and an iterated stockholder atom (ISA) partitioning of the molecular electron density. We demonstrate that this Slater–ISA methodology yields a more accurate, transferable, and robust description of the short-range interactions at minimal additional computational cost compared to standard Lennard-Jones or Born–Mayer approaches. Finally, we show how this methodology can be adapted to yield the standard Born–Mayer functional form while still retaining many of the advantages of the Slater-ISA approach.

The recently developed iterated stockholder atoms (ISA) approach of Lillestolen and Wheatley (Chem. Commun.2008, 5909) offers a powerful method for defining atoms in a molecule. However, the real-space algorithm is known to converge very slowly, if at all. Here, we present a robust, basis-space algorithm of the ISA method and demonstrate its applicability on a variety of systems. We show that this algorithm exhibits rapid convergence (taking around 10–80 iterations) with the number of iterations needed being unrelated to the system size or basis set used. Further, we show that the multipole moments calculated using this basis-space ISA method are as good as, or better than, those obtained from Stone’s distributed multipole analysis (J. Chem. Theory Comput.2005, 1, 1128), exhibiting better convergence properties and resulting in better behaved penetration energies. This can have significant consequences in the development of intermolecular interaction models.

The charge-transfer (CT) together with the polarization energy appears at second and higher orders in symmetry-adapted perturbation theory (SAPT). At present there is no theoretically compelling way of isolating the charge-transfer energy that is simultaneously basis-set independent and applicable for arbitrary intermolecular separation. We argue that the charge-transfer can be interpreted as a tunneling phenomenon and can therefore be defined via regularized SAPT. This leads to a physically convincing, basis-independent definition of the charge-transfer energy that captures subtleties of the process, such as the asymmetry in the forward and backward charge transfer, as well as secondary transfer effects. With this definition of the charge-transfer the damping needed for polarization models can be determined with a level of confidence hitherto not possible.

Standard empirical atom−atom potentials are shown to be unable to describe the binding of polycyclic aromatic hydrocarbon (PAH) molecules in the variety of configurations seen in clusters. The main reason for this inadequacy is the lack of anisotropy in these potentials. We have constructed an anisotropic atom−atom intermolecular potential for the benzene molecule from first principles using a symmetry-adapted perturbation theory based on density functional theory (SAPT(DFT)), interaction energy calculations and the Williams−Stone−Misquitta method for obtaining molecular properties in distributed form. Using this potential as a starting point, we have constructed a transferable anisotropic potential to model intermolecular interactions between PAHs. This new potential has been shown to accurately model interaction energies for a variety of dimer configurations for four different PAH molecules, including certain configurations which are poorly modeled with current isotropic potentials. It is intended that this potential will form the basis for further work on the aggregation of PAHs.

Regulation and expression of E-cadherin and other adhesion molecules were evaluated after exposure to a selective inhibitor of the Src family of tyrosine kinases and inducer of E-cadherin, PP2. E-cadherin is located within the intercellular junction, and it is involved in the management of paracellular permeability of various epithelial barriers in the body. Epithelial cell lines HCT-116, HT29, Caco-2, LS174T, and ARPE-19 were examined for morphological, functional, protein, and mRNA changes following 20 μM PP2 treatment. PP2 treatment caused cell clustering in Caco-2, HT29, and HCT-116 cells. E-cadherin also redistributed to the points of cell contact in Caco-2 cells. These changes suggest increased E-cadherin-dependent cell adhesion. Studies evaluating transepithelial electrical resistance, an established measurement of paracellular permeability, displayed increases in resistance for the Caco-2 cells following PP2 treatment, which correlates with our microscopy data. In addition, E-cadherin protein levels increased for all cells except HCT-116. ARPE-19 cells did not express E-cadherin at the protein or mRNA level. Expression of adhesion molecules varied for the cell lines, and only Claudin 3 mRNA expression was significantly increased in the three intestinal cell lines treated with PP2. Overall, our data suggest that E-cadherin is positively regulated by inhibition of Src tyrosine kinases at the functional and protein expression levels within these epithelial cell lines. Keywords: E-cadherin; paracellular drug delivery; adhesion molecules; epithelial cells; PP2; SRC inhibitors

At-home bleaching with 10 percent carbamide peroxide in a custom-fitted tray has been reported to change the color of dentin. The purpose of this study was to validate the color change of dentin and to determine whether the color change was uniform or occurred from the outside (the dentinoenamel junction) to the inside (the pulpal wall).

Adolf Weil defined the disease as a clinical entity in 1886, and Leptospira ictero-hæmorrhagiæwas found to be the causative organism in 1915 by Inada et al.in Japan, and confirmed by Hübener and Reiter in Germany. The infection has been found in most countries, and recently there has been a great increase in the number of instances reported.In most parts of the world rats and other small rodents harbour the organism and excrete it in the urine. This is almost always the direct or indirect source of infection of man, but natural infection of dogs and foxes takes place, and is at least a potential danger to human beings. Infection is usually related to occupation in coal-mines, field work of all sorts, sewers, fish-cleaning, and to bathing in fresh water.The organism quickly dies in an acid medium, in strong sunlight and in salt water. These facts accord with the presence of the disease in certain situations.The route of infection of man is usually by contact of the abraded or sodden skin with infected mud or water, but it may be by inhalation of water and by bites of rats, dogs, and ferrets.Men are much more exposed to infection than women, but in fish-cleaners the incidence is equal in the sexes. Children are sometimes infected by bathing and in houses.The incubation time may be four to nineteen days, and is usually seven to thirteen days.By serological methods many unjaundiced and subclinical infections can be detected among people who are often at risk, and these correct the rather high fatality rates which are derived from jaundiced cases only.During the last three and a half years 142 authenticated instances of the disease in an obvious clinical form have been reported in the British Isles. Twenty-one occupations or circumstances were involved, and the case fatality rate was 15 per cent.

Tris-disrupted and intact brush border membrane preparations from mucosa of hamster jejunum were capable of preferentially binding actively transported D-glucose in a similar manner. Density gradient centrifugation of the Tris-disrupted brush borders indicated that D-glucose was bound to a fraction containing the cores or inner material of the microvilli. The properties of this binding were examined with the Tris-disrupted brush border preparation. Actively transported sugars competitively inhibited preferential D-glucose binding, whereas no effect was observed with nonactively transported sugars. Neither actively nor nonactively transported amino acids affected D-glucose binding. D-Glucosamine, which is not actively transported, was inhibitory to preferential D-glucose binding as well as to the active transport of D-glucose by everted sacs of hamster jejunum. No inhibitory effect was observed with the same concentration of D-galactosamine. Preferential D-glucose binding was also inhibited by sulfhydryl-reacting compounds, Ca2+, and Li+ ions. On the other hand, Mg2+ was shown to be stimulatory and Na+, NH4+, and K+ had no effect on this phenomenon. The results of these experiments suggest that preferential D-glucose binding to brush borders is related to the initial step in active sugar transport by the small intestine.

Several letters to the editor are presented in response to the articles in previous issues including a column about television production in the August 25, 1986 issue, on issues about the cover line for annual mutual funds survey "The Maddening Multiplicity Of Funds" in the September 8, 1986 issue, and Kenneth Bartley Boudrie's furniture reproduction business in the July 28, 1986 issue.

Which is the best reference quantum chemical approach to decipher the energy components of the total interaction energy: Symmetry-Adapted Perturbation Theory (SAPT) or Supermolecular Energy Decomposition Analysis (EDA) methods? With the rise of physically motivated polarizable force fields (polFF) grounded on these procedures, the need to answer such a question becomes critical. We report a systematic and detailed assessment of three variants of SAPT (namely SAPT2, SAPT2+3, and SAPT(DFT)) and three supermolecular EDA approaches (ALMO, CSOV, and RVS). A set of challenging, strongly bound water complexes, (H2O)2, Zn2+. . .H2O, and F–. . .H2O, is used as “stress tests” for these electronic structure methods. We have developed a procedure to separate the induction energy into the polarization and charge-delocalization using an infinite-order strategy based on SAPT(DFT). This paper aims to provide not only an overview of the capabilities and limitations but also similarities of SAPT and supermolecular EDA approaches for polFF developments. Our results show that SAPT(DFT)/noS2and ωB97X-D∥ALMO are the most accurate and reliable techniques.