Formation of ice-like water structure on the surface of an antifreeze protein

Antifreeze proteins (AFPs) are found in different species from polar, alpine, and subarctic regions where they serve to inhibit ice crystal growth by adsorption to ice surfaces. Computational methods have the power to investigate the antifreeze mechanism in atomic detail. Molecular dynamics simulations of water under different conditions have been carried out to test our water model for simulations of biological macromolecules in extreme conditions: very low temperatures (200 K) and at the ice/liquid water interface. We show that the flexible F3C water model reproduces properties of water in the solid phase (ice I(h)), the supercooled liquid phase, and at the ice/liquid water interface. Additionally, the hydration of the type III AFP from ocean pout was studied as a function of temperature. Hydration waters on the ice-binding surface of the AFP were less distorted and more tetrahedral than elsewhere on the surface. More ice-like hydrating water structures formed on the ice-binding surface of the protein such that it created an ice-like structure in water within its first hydration layer but not beyond, suggesting that this portion of the protein has high affinity for ice surfaces.     

Evolving interpretable structure-activity relationships. 1. Reduced graph queries

A new machine learning method is presented for extracting interpretable structure-activity relationships from screening data. The method is based on an evolutionary algorithm and reduced graphs and aims to evolve a reduced graph query (subgraph) that is present within the active compounds and absent from the inactives. The reduced graph representation enables heterogeneous compounds, such as those found in high-throughput screening data, to be captured in a single representation with the resulting query encoding structure-activity information in a form that is readily interpretable by a chemist. The application of the method is illustrated using data sets extracted from the well-known MDDR data set and GSK in-house screening data. Queries are evolved that are consistent with the known SARs, and they are also shown to be robust when applied to independent sets that were not used in training.     

Diastereoselective Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan catalyzed by bismuth triflate

We have developed an efficient vinylogous Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan with various aromatic aldehydes mediated by bismuth triflate in low catalyst loading (1 mol %). The reaction proceeds rapidly and affords the corresponding 5-(hydroxy(aryl)methyl)furan-2(5H)-ones in high yields with good to very good diastereoselectivities (dr up to >98:2). Such selectivities, albeit previously reported with other Lewis acids, could this time be achieved with a much lower catalyst loading. 5-(Hydroxy(alkyl)methyl)furan-2(5H)-ones derived from ketones could also be obtained with good diastereoselectivities.     

Ambient air monitoring with Auto-gas chromatography running in trigger mode

Speciated volatile organic compounds (VOC), either as ozone precursors or air toxics in the air, are commonly monitored by triggered canister method or continuous ozone precursor analyzer (commonly known as Auto-gas chromatography (GC)) method. In the triggered canister method, a canister sample is collected when a total non-methane organic compound (TNMOC) concentration exceeds a pre-determined trigger level. The canister sample is then analyzed in a lab in a later time. In the Auto-GC method, an online GC runs in a “continuous” mode with a sampling and analysis cycle of 1 h. Within the cycle hour, samples are collected only during the first 40 min.A new approach of Auto-GC running in trigger mode is developed in this study. This new approach uses Auto-GC but operates it in a trigger mode similar to the triggered canister sampling method. Compared to the triggered canister sample method, this system provides near real-time speciated VOC data, which are critical for responding to a high VOC concentration episode. Although the canister system generally costs less, its cost advantage may diminish if trigger events are frequent and the monitoring duration is long. Compared to continuous Auto-GC, triggered GC has its niche—it is better for capturing transient plumes with a small footprint. The continuous GC either misses a transient plume if the plume does not arrive at the sampling site during the sampling cycle or flattens the plume concentration peak by dilution with non-plume air sample.Field experience with this system for fenceline VOC monitoring is presented. The sampling and calibration strategy for trigger mode operation is described. The chromatograph retention time drift issues are discussed. The system performance is evaluated, including the method detection limit, precision and accuracy. The trigger mode configuration for VOC fenceline or near source monitoring in this work proved effective for local and transient plume identification.     

Fermi resonance in CO2: a combined electronic coupled-cluster and vibrational configuration-interaction prediction

The authors present a first-principles prediction of the energies of the eight lowest-lying anharmonic vibrational states of CO(2), including the fundamental symmetric stretching mode and the first overtone of the fundamental bending mode, which undergo a strong coupling known as Fermi resonance. They employ coupled-cluster singles, doubles, and (perturbative) triples [CCSD(T) and CCSDT] in conjunction with a range of Gaussian basis sets (up to cc-pV5Z, aug-cc-pVQZ, and aug-cc-pCVTZ) to calculate the potential energy surfaces (PESs) of the molecule, with the errors arising from the finite basis-set sizes eliminated by extrapolation. The resulting vibrational many-body problem is solved by the vibrational self-consistent-field and vibrational configuration-interaction (VCI) methods with the PESs represented by a fourth-order Taylor expansion or by numerical values on a Gauss-Hermite quadrature grid. With the VCI, the best theoretical estimates of the anharmonic energy levels agree excellently with experimental values within 3.5 cm(-1) (the mean absolute deviation). The theoretical (experimental) anharmonic frequencies of the Fermi doublet are 1288.9 (1285.4) and 1389.3 (1388.2) cm(-1).     

Thermal and vibrational characterization of human skin

For a better understanding of the molecular and organizational changes in human dermis, biophysical methods were tested. The aim of this study was to find suitable and reproducible biomarkers for further clinical studies on intrinsic and extrinsic aging of dermis. Thermoporometry, hydric organization and thermal transitions of fresh and frozen skins were determined by differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) was used to identify the absorption bands of the dermis especially in the 1800–1000 cm^?1 zone and to discriminate between the different secondary structures of proteins. A widening of the pore size distribution is evidenced with freezing, but there is no significant difference between the hydric organization and the endothermic collagen denaturation of fresh and frozen skins. The global FTIR spectra and the second derivative spectra in the scanned zone are also identical in fresh and frozen dermis, validating the storage protocol. DSC and FTIR are well-suited techniques to characterize human skin, giving accurate results with high reproducibility. The acquisition of thermal and vibrational biomarkers of the skin at the mesoscale and nanoscale contributes to its better knowledge and is promising for further studies on skin aging.     

Towards hyperpolarized (13)C-succinate imaging of brain cancer

We describe a novel (13)C enriched precursor molecule, sodium 1-(13)C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized (13)C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized (13)C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized (13)C sodium succinate, contained significant concentrations of the injected substrate, (13)C sodium succinate, together with (13)C maleate and succinate metabolites 1-(13)C-glutamate, 5-(13)C-glutamate, 1-(13)C-glutamine and 5-(13)C-glutamine. The (13)C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized (13)C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in (13)C MR spectral-spatial images.     

Aromatic and nonaromatic pyriporphyrins

Pyriporphyrins with three different orientations for the pyridine moiety have been prepared using a '3 + 1' strategy. The nonaromatic pyriporphyrins are stable so long as phenyl substituents are present at the meso-positions adjacent to the pyridine ring. An aromatic dihydropyriporphyrin with an external CO2Ph protective group has also been prepared from 2,4-pyridinedicarbaldehyde.     

Ultrasonically determined thickness of long cortical bones: two-dimensional simulations of in vitro experiments

Previously it has been demonstrated that cortical bone thickness can be estimated from ultrasonic guided-wave measurements, in an axial transmission configuration, together with an appropriate analytical model. This study considers the impact of bone thickness variation within the measurement region on the ultrasonically determined thickness (UTh). To this end, wave velocities and UTh were determined from experiments and from time-domain finite-difference simulations of wave propagation, both performed on a set of ten human radius specimens (29 measurement sites). A two-dimensional numerical bone model was developed with tunable material properties and individualized geometry based on x-ray computed-tomography reconstructions of human radius. Cortical thickness (CTh) was determined from the latter. UTh data for simulations were indeed in a excellent accordance (root-mean-square error was 0.26 mm; r2=0.94, p<0.001) with average CTh within the measurement region. These results indicate that despite variations in cortical thickness along the propagation path, the measured phase velocity can be satisfactorily modeled by a simple analytical model (the A(0) plate mode in this case). Most of the variability (up to 85% when sites were carefully matched) observed in the in vitro ultrasound data was explained through simulations by variability in the cortical thickness alone.     

Acoustic scattering in dispersions: improvements in the calculation of single particle scattering coefficients

Measurements of ultrasound speed and attenuation can be related to the properties of dispersed systems by applying a scattering model. Rayleigh's method for scattering of sound by a spherical object, and its subsequent developments to include viscous, thermal, and other effects (known as the ECAH model) has been widely adopted. The ECAH method has difficulties, including numerical ill-conditioning, calculation of Bessel functions at large arguments, and inclusion of thermal effects in all cases. The present work develops techniques for improving the ECAH calculations to allow its use in instrumentation. It is shown that thermal terms can be neglected in some boundary equations up to approximately 100 GHz in water, and several simplified solutions result. An analytical solution for the zero-order coefficient is presented, with separate nonthermal and thermal parts, allowing estimation of the thermal contribution. Higher orders have been simplified by estimating the small shear contribution as the inertial limit is approached. The condition of the matrix solutions have been greatly improved by these techniques and by including appropriate scaling factors. A method is presented for calculating the required Bessel functions when the argument is large (high frequency or large particle size). The required number of partial wave orders is also considered.