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Ab initio chemical shielding calculations greatly facilitate the interpretation of nuclear magnetic resonance (NMR) chemical shifts in biological systems, but the large sizes of these systems requires approximations in the chemical models used to represent them. Achieving good convergence in the predicted chemical shieldings is necessary before one can unravel how other complex structural and dynamical factors affect the NMR measurements. Here, we investigate how to balance trade-offs between using a better basis set or a larger cluster model for predicting the chemical shieldings of the substrates in two representative examples of protein-substrate systems involving different domains in tryptophan synthase: the N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl phosphate (F9) ligand which binds in the α active site, and the 2-aminophenol quinonoid intermediate formed in the β active site. We first demonstrate that a chemically intuitive three-layer, locally dense basis model that uses a large basis on the substrate, a medium triple-zeta basis to describe its hydrogen-bonding partners and/or surrounding van der Waals cavity, and a crude basis set for more distant atoms provides chemical shieldings in good agreement with much more expensive large basis calculations. Second, long-range quantum mechanical interactions are important, and one can accurately estimate them as a small-basis correction to larger-basis calculations on a smaller cluster. The combination of these approaches enables one to perform density functional theory NMR chemical shift calculations in protein systems that are well-converged with respect to both basis set and cluster size.

Introduction: Self-concealment reflects uncomfortable feelings, thoughts, and information people have about themselves that they avoid telling others (Larson & Chastain, 1990). According to Larson and Chastain (1990) these secrets range from the slightly embarrassing to the very distressing with an individual's most traumatic experiences often concealed. Parental attitudes including those involving self-disclosure are thought to be expressed in their choice of parenting style (Brand, Hatzinger, Beck, & Holsboer-Trachsler, 2009). The specific aim of this investigation was to examine the direct and indirect influences of parenting styles on self-concealment, impaired control over drinking (i.e. the inability to stop drinking when intended), alcohol use (quantity/frequency), and alcohol-related problems., Methods: A structural equation model with 419 (223 men, 196 women) university students was examined. Two and three path mediated effects were examined with the bias corrected bootstrap technique in Mplus., Results: Having an authoritarian mother was directly linked to more self-concealment, while having an authoritative father was directly linked to less self-concealment. Higher levels of mother authoritarianism were indirectly linked to both increased alcohol use and alcohol-related problems through more self-concealment and more impaired control over drinking. Moreover, higher levels of father authoritativeness were indirectly linked to less alcohol use and alcohol-related problems through less self-concealment and less impaired control over drinking., Conclusions: These findings suggest that parenting styles influence vulnerabilities such as self-concealment in the impaired control over the drinking pathway to alcohol use and alcohol-related problems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

First-principles chemical shielding tensor predictions play a critical role in studying molecular crystal structures using nuclear magnetic resonance. Fragment-based electronic structure methods have dramatically improved the ability to model molecular crystal structures and energetics using high-level electronic structure methods. Here, a many-body expansion fragment approach is applied to the calculation of chemical shielding tensors in molecular crystals. First, the impact of truncating the many-body expansion at different orders and the role of electrostatic embedding are examined on a series of molecular clusters extracted from molecular crystals. Second, the ability of these techniques to assign three polymorphic forms of the drug sulfanilamide to the corresponding experimental (13)C spectra is assessed. This challenging example requires discriminating among spectra whose (13)C chemical shifts differ by only a few parts per million (ppm) across the different polymorphs. Fragment-based PBE0/6-311+G(2d,p) level chemical shielding predictions correctly assign these three polymorphs and reproduce the sulfanilamide experimental (13)C chemical shifts with 1 ppm accuracy. The results demonstrate that fragment approaches are competitive with the widely used gauge-invariant projector augmented wave (GIPAW) periodic density functional theory calculations.

Controlling charge transfer at a molecular scale is critical for efficient light harvesting, energy conversion, and nanoelectronics. Dipole-polarization electrets, the electrostatic analogue of magnets, provide a means for "steering" electron transduction via the local electric fields generated by their permanent electric dipoles. Here, we describe the first demonstration of the utility of anthranilamides, moieties with ordered dipoles, for controlling intramolecular charge transfer. Donor-acceptor dyads, each containing a single anthranilamide moiety, distinctly rectify both the forward photoinduced electron transfer and the subsequent charge recombination. Changes in the observed charge-transfer kinetics as a function of media polarity were consistent with the anticipated effects of the anthranilamide molecular dipoles on the rectification. The regioselectivity of electron transfer and the molecular dynamics of the dyads further modulated the observed kinetics, particularly for charge recombination. These findings reveal the underlying complexity of dipole-induced effects on electron transfer and demonstrate unexplored paradigms for molecular rectifiers.

The Kepler spacecraft is monitoring more than 150,000 stars for evidence of planets transiting those stars. We report the detection of two Saturn-size planets that transit the same Sun-like star, based on 7 months of Kepler observations. Their 19.2- and 38.9-day periods are presently increasing and decreasing at respective average rates of 4 and 39 minutes per orbit; in addition, the transit times of the inner body display an alternating variation of smaller amplitude. These signatures are characteristic of gravitational interaction of two planets near a 2:1 orbital resonance. Six radial-velocity observations show that these two planets are the most massive objects orbiting close to the star and substantially improve the estimates of their masses. After removing the signal of the two confirmed giant planets, we identified an additional transiting super-Earth-size planet candidate with a period of 1.6 days.

Stellar-mass black holes are found in X-ray-emitting binary systems, where their mass can be determined from the dynamics of their companion stars. Models of stellar evolution have difficulty producing black holes in close binaries with masses more than ten times that of the Sun (>10; ref. 4), which is consistent with the fact that the most massive stellar black holes known so far all have masses within one standard deviation of 10. Here we report a mass of (15.65 +/- 1.45) for the black hole in the recently discovered system M 33 X-7, which is located in the nearby galaxy Messier 33 (M 33) and is the only known black hole that is in an eclipsing binary. To produce such a massive black hole, the progenitor star must have retained much of its outer envelope until after helium fusion in the core was completed. On the other hand, in order for the black hole to be in its present 3.45-day orbit about its (70.0 +/- 6.9) companion, there must have been a 'common envelope' phase of evolution in which a significant amount of mass was lost from the system. We find that the common envelope phase could not have occurred in M 33 X-7 unless the amount of mass lost from the progenitor during its evolution was an order of magnitude less than what is usually assumed in evolutionary models of massive stars.

We report a case of aortic, coronary, and renal artery dissections associated with pregnancy. The histologic changes related to the hemorrhages included smooth-muscle cell (SMC) proliferation with fibrosis, elastin fragmentation and collagen degeneration, and SMC vacuolar degeneration and coagulation necrosis. These lesions seemed to be prototypes for dissection, since they were associated with aortic and muscular artery dissections in three additional cases unrelated to pregnancy. In each case, dissections seemed to result from SMC activity that also involved the systemic vasculature, veins, and visceral smooth muscle in histologic patterns that could be explained as a product of SMC metabolism. We propose that the histologic changes associated with dissections are best explained as a product of the metabolism of SMCs that function as multifunctional mesenchyma in a manner controlled by variable penetrance of a gene that controls their metabolism.

From observations on 454 coronary arteries from subjects ranging in age from prematurely newborn to 90 years, six structural patterns of medial smooth muscle are interpreted as representing, or related to, the proliferation and/or migration of medial smooth muscle into intima. By measuring the extent of inner medial circumference occupied by four of the six patterns, it was possible to calculate a numerical value designated the medial proliferatice and / or migratory activity (MP-MA) of each artery. During the first three decades, nonatherosclerotic diffuse intimal thickening was the characteristic intimal process, and during this phase of the arterial maturation span, the MP-MA of the arteries was significantly related to the degree of intimal thickening. Following a peak MP-MA level by the end of the third decade, there was a progressive decrease in the MP-MA level as the incidence and severity of atherosclerotic intimal thickening increased. At advanced stages of atherosclerotic intimal thickening, which were associated with thinning of adjacent media, intimal-medial structural patterns indicating a relationship between medial smooth muscle proliferative activity and the expanding atherosclerotic plaque were also apparent. The observations support the concept that the movement of medial smooth muscle into intima is a critical step preceding and during the evolution of the atherosclerotic plaque.

8-Cyclopentyl-1,3-dipropylxanthine (PD 116,948) is a very potent, very A1-selective adenosine antagonist, with a Ki of 0.46 nM in 3H-CHA binding to A1 receptors in rat whole brain membranes and 340 nM in 3H-NECA binding to A2 receptors in rat striatal membranes. Its 740-fold A1-selectivity is the highest reported for an adenosine antagonist. 3H-PD 116,948 (117 Ci/mmol) was prepared by reduction of the diallyl analog. 3H-PD 116,948 bound to a single site in rat whole brain membranes, with a Bmax of 46 pmol/g wet weight and Kd of 0.42 nM. Nonspecific binding was extremely low, amounting to about 3% of total binding under standard conditions and less than 1% when higher tissue concentrations were used. Affinities of compounds for inhibition of 3H-PD 116,948 binding were highly consistent with an A1 adenosine receptor. Antagonists were equally potent in 3H-PD 116,948 binding and in 3H-CHA binding, while agonists were consistently about 12-fold more potent in 3H-CHA binding. Hill coefficients were 1.0 for antagonists and about 0.65 for agonists. 3H-PD 116,948 should be a useful antagonist ligand for adenosine A1 receptors.