Universal Correction of Density Functional Theory to Include London Dispersion (up to Lr, Element 103)

Conventional density functional theory (DFT) fails to describe accurately the London dispersion essential for describing molecular interactions in soft matter (biological systems, polymers, nucleic acids) and molecular crystals. This has led to several methods in which atom-dependent potentials are added into the Kohn–Sham DFT energy. Some of these corrections were fitted to accurate quantum mechanical results, but it will be tedious to determine the appropriate parameters to describe all of the atoms of the periodic table. We propose an alternative approach in which a single parameter in the low-gradient (lg) functional form is combined with the rule-based UFF (universal force-field) nonbond parameters developed for the entire periodic table (up to Lr, Z = 103), named as a DFT-ulg method. We show that DFT-ulg method leads to a very accurate description of the properties for molecular complexes and molecular crystals, providing the means for predicting more accurate weak interactions across the periodic table

Influenza A H1N1 Pandemic Strain Evolution – Divergence and the Potential for Antigenic Drift Variants

The emergence of a novel A(H1N1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. We examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) segments of the A(H1N1)pdm09 strain using publicly available data. We calculated the nucleotide and amino acid hamming distance from the vaccine strain A/California/07/2009 for each sequence. We also estimated Pepitope–a measure of antigenic diversity based on changes in the epitope regions–for each isolate. Finally, we compared our results to A(H3N2) strains collected over the same period. Our analysis found that the mean hamming distance for the HA protein of the A(H1N1)pdm09 strain increased from 3.6 (standard deviation [SD]: 1.3) in 2009 to 11.7 (SD: 1.0) in 2013, while the mean hamming distance in the coding region increased from 7.4 (SD: 2.2) in 2009 to 28.3 (SD: 2.1) in 2013. These trends are broadly similar to the rate of mutation in H3N2 over the same time period. However, in contrast to H3N2 strains, the rate of mutation accumulation has slowed in recent years. Our results are notable because, over the course of the study, mutation rates in H3N2 similar to that seen with A(H1N1)pdm09 led to the emergence of two antigenic drift variants. However, while there has been an H1N1 epidemic in North America this season, evidence to date indicates the vaccine is still effective, suggesting the epidemic is not due to the emergence of an antigenic drift variant. Our results suggest that more research is needed to understand how viral mutations are related to vaccine effectiveness so that future vaccine choices and development can be more predictive

Graph’s Topology and Free Energy of a Spin Model on the Graph

In this work we show that there is a direct relationship between a graph's topology and the free energy of a spin system on the graph. We develop a method of separating topological and enthalpic contributions to the free energy, and find that considering the topology is sufficient to qualitatively compare the free energies of different graph systems at high temperature, even when the energetics are not fully known. This method was applied to the metal lattice system with defects, and we found that it partially explains why point defects are more stable than high-dimensional defects. Given the energetics, we can even quantitatively compare free energies of different graph structures via a closed form of linear graph contributions. The closed form is applied to predict the sequence space free energy of lattice proteins, which is a key factor determining the designability of a protein structure.Chemistry and Chemical Biolog

Atelectasis Induced by Thoracotomy Causes Lung Injury during Mechanical Ventilation in Endotoxemic Rats

Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (iNOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an iNOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through iNOS expression

Cutaneous Schwannoma Presented as a Pedunculated Protruding Mass

Schwannoma is a benign neoplasm of the nerve sheath origin. It arises from the nerve sheath of large peripheral or cranial nerves and occurs at the level of the subcutaneous fat layer or deeper layer. Cutaneous schwannoma occurs more superficially and usually presents as a solitary dermal or subcutaneous nodule. We describe a case of cutaneous schwannoma that presented as an erythematous pedunculated protruding mass on the left flank of a 19-year-old female. It was clinically diagnosed as a granuloma pyogenicum. Shaving biopsy was conducted and histological examination revealed an encapsulated tumor mass containing dense, spindle-shaped cells whose nuclei are arranged back to back representing Verocay body, and a diagnosis of schwannoma was made. This is an unusual case of cutaneous schwannoma that presented as a pedunculated protruding mass