Expanding and Testing a Computational Method for Predicting the Ground State Reduction Potentials of Organic Molecules on the Basis of Empirical Correlation to Experiment

A method for predicting the ground state reduction potentials of organic molecules on the basis of the correlation of computed energy differences between the starting S-0 and one-electron-reduced D-0 species with experimental reduction potentials in acetonitrile has been expanded to cover 3.5 V of potential range and 74 compounds across 6 broad families of molecules. Utilizing the conductor-like polarizable continuum model of implicit solvent allows a global correlation that is computationally efficient and has improved accuracy, with r(2) \u3e 0.98 in all cases and root mean square deviation errors of(mean absolute deviationsmV) for either B3LYP/6-311+G(d,p) or B3LYP//6-31G(d) with an appropriate choice of radii (UAKS or UA0). The correlations are proven to be robust across a wide range of structures and potentials, including four larger (27-28 heavy atoms) and more conformationally flexible photochromic molecules not used in calibrating the correlation. The method is also proven to be robust to a number of minor student mistakes or methodological inconsistencies

EXCEDE Technology Development III: First Vacuum Tests

This paper is the third in the series on the technology development for the EXCEDE (EXoplanetary Circumstellar Environments and Disk Explorer) mission concept, which in 2011 was selected by NASA's Explorer program for technology development (Category III). EXCEDE is a 0.7m space telescope concept designed to achieve raw contrasts of 1e6 at an inner working angle of 1.2 l/D and 1e7 at 2 l/D and beyond. This will allow it to directly detect and spatially resolve low surface brightness circumstellar debris disks as well as image giant planets as close as in the habitable zones of their host stars. In addition to doing fundamental science on debris disks, EXCEDE will also serve as a technological and scientific precursor for any future exo-Earth imaging mission. EXCEDE uses a Starlight Suppression System (SSS) based on the PIAA coronagraph, enabling aggressive performance. We report on our continuing progress of developing the SSS for EXCEDE, and in particular (a) the reconfiguration of our system into a more flight-like layout, with an upstream deformable mirror and an inverse PIAA system, as well as a LOWFS, and (b) testing this system in a vacuum chamber, including IWA, contrast, and stability performance. The results achieved so far are 2.9e-7 contrast between 1.2-2.0 l/D and 9.7e-8 contrast between 2.0-6.0 l/D in monochromatic light; as well as 1.4e-6 between 2.0-6.0 l/D in a 10% band, all with a PIAA coronagraph operating at an inner working angle of 1.2 l/D. This constitutes better contrast than EXCEDE requirements (in those regions) in monochromatic light, and progress towards requirements in broadband light. Even though this technology development is primarily targeted towards EXCEDE, it is also germane to any exoplanet direct imaging space-based telescopes because of the many challenges common to different coronagraph architectures and mission requirements.Comment: 12 pages, 12 figures, to be published in proceedings of SPIE Astronomical Telescopes + Instrumentation (2014

Synthesis and Structural Investigation of an \u27Oxazinoquinolinespirohexadienone\u27 That Only Exists as Its Long-Wavelength Ring-Opened Quinonimine Isomer

The spirocyclic oxazinoquinolinespirohexadienone (OSHD) photochromes are computationally predicted to be an attractive target as electron deficient analogues of the perimidinespirohexadienone (PSHD) photochromes, for eventual application as photochromic photooxidants. We have found the literature method for their preparation unsuitable and present an alternative synthesis. Unfortunately the product of this synthesis is the long wavelength (LW) ring-opened quinonimine isomer of the OSHD. We have found this isomer does not close to the spirocyclic short wavelength isomer (SW) upon prolonged standing in the dark, unlike other PSHD photochromes. The structure of this long wavelength isomer was found by NMR and X-ray crystallography to be exclusively the quinolinone (keto) tautomer, though experimental cyclic voltammetry supported by our computational methodology indicates that the quinolinol (enol) tautomer (not detected by other means) may be accessible through a fast equilibrium lying far toward the keto tautomer. Computations also support the relative stability order of keto LW over enol LW over SW

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome

Considerations for best practices in studies of fiber or other dietary components and the intestinal microbiome. Am J Physiol Endocrinol Metab 315: E1087–E1097, 2018. First published August 21, 2018; doi:10.1152/ajpendo.00058.2018.—A 2-day workshop organized by the National Institutes of Health and U.S. Department of Agriculture included 16 presentations focused on the role of diet in alterations of the gastrointestinal microbiome, primarily that of the colon. Although thousands of research projects have been funded by U.S. federal agencies to study the intestinal microbiome of humans and a variety of animal models, only a minority addresses dietary effects, and a small subset is described in sufficient detail to allow reproduction of a study. Whereas there are standards being developed for many aspects of microbiome studies, such as sample collection, nucleic acid extraction, data handling, etc., none has been proposed for the dietary component; thus this workshop focused on the latter specific point. It is important to foster rigor in design and reproducibility of published studies to maintain high quality and enable designs that can be compared in systematic reviews. Speakers addressed the influence of the structure of the fermentable carbohydrate on the microbiota and the variables to consider in design of studies using animals, in vitro models, and human subjects. For all types of studies, strengths and weaknesses of various designs were highlighted, and for human studies, comparisons between controlled feeding and observational designs were discussed. Because of the lack of published, best-diet formulations for specific research questions, the main recommendation is to describe dietary ingredients and treatments in as much detail as possible to allow reproduction by other scientists

Independent repeated mutations within the alphaviruses Ross River virus and Barmah Forest virus indicates convergent evolution and past positive selection in ancestral populations despite ongoing purifying selection

Ross River virus (RRV) and Barmah Forest virus (BFV) are arthritogenic arthropod-borne viruses (arboviruses) that exhibit generalist host associations and share distributions in Australia and Papua New Guinea (PNG). Using stochastic mapping and discrete-trait phylogenetic analyses, we profiled the independent evolution of RRV and BFV signature mutations. Analysis of 186 RRV and 88 BFV genomes demonstrated their viral evolution trajectories have involved repeated selection of mutations, particularly in the nonstructural protein 1 (nsP1) and envelope 3 (E3) genes suggesting convergent evolution. Convergent mutations in the nsP1 genes of RRV (residues 248 and 441) and BFV (residues 297 and 447) may be involved with catalytic enzyme mechanisms and host membrane interactions during viral RNA replication and capping. Convergent E3 mutations (RRV site 59 and BFV site 57) may be associated with enzymatic furin activity and cleavage of E3 from protein precursors assisting viral maturation and infectivity. Given their requirement to replicate in disparate insect and vertebrate hosts, convergent evolution in RRV and BFV may represent a dynamic link between their requirement to selectively ‘fine-tune’ intracellular host interactions and viral replicative enzymatic processes. Despite evidence of evolutionary convergence, selection pressure analyses did not reveal any RRV or BFV amino acid sites under strong positive selection and only weak positive selection for nonstructural protein sites. These findings may indicate that their alphavirus ancestors were subject to positive selection events which predisposed ongoing pervasive convergent evolution, and this largely supports continued purifying selection in RRV and BFV populations during their replication in mosquito and vertebrate hosts

A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes

Protein-coding genes in eukaryotes are interrupted by introns, but intron densities widely differ between eukaryotic lineages. Vertebrates, some invertebrates and green plants have intron-rich genes, with 6–7 introns per kilobase of coding sequence, whereas most of the other eukaryotes have intron-poor genes. We reconstructed the history of intron gain and loss using a probabilistic Markov model (Markov Chain Monte Carlo, MCMC) on 245 orthologous genes from 99 genomes representing the three of the five supergroups of eukaryotes for which multiple genome sequences are available. Intron-rich ancestors are confidently reconstructed for each major group, with 53 to 74% of the human intron density inferred with 95% confidence for the Last Eukaryotic Common Ancestor (LECA). The results of the MCMC reconstruction are compared with the reconstructions obtained using Maximum Likelihood (ML) and Dollo parsimony methods. An excellent agreement between the MCMC and ML inferences is demonstrated whereas Dollo parsimony introduces a noticeable bias in the estimations, typically yielding lower ancestral intron densities than MCMC and ML. Evolution of eukaryotic genes was dominated by intron loss, with substantial gain only at the bases of several major branches including plants and animals. The highest intron density, 120 to 130% of the human value, is inferred for the last common ancestor of animals. The reconstruction shows that the entire line of descent from LECA to mammals was intron-rich, a state conducive to the evolution of alternative splicing

Localized Plasticity in the Streamlined Genomes of Vinyl Chloride Respiring Dehalococcoides

Vinyl chloride (VC) is a human carcinogen and widespread priority pollutant. Here we report the first, to our knowledge, complete genome sequences of microorganisms able to respire VC, Dehalococcoides sp. strains VS and BAV1. Notably, the respective VC reductase encoding genes, vcrAB and bvcAB, were found embedded in distinct genomic islands (GEIs) with different predicted integration sites, suggesting that these genes were acquired horizontally and independently by distinct mechanisms. A comparative analysis that included two previously sequenced Dehalococcoides genomes revealed a contextually conserved core that is interrupted by two high plasticity regions (HPRs) near the Ori. These HPRs contain the majority of GEIs and strain-specific genes identified in the four Dehalococcoides genomes, an elevated number of repeated elements including insertion sequences (IS), as well as 91 of 96 rdhAB, genes that putatively encode terminal reductases in organohalide respiration. Only three core rdhA orthologous groups were identified, and only one of these groups is supported by synteny. The low number of core rdhAB, contrasted with the high rdhAB numbers per genome (up to 36 in strain VS), as well as their colocalization with GEIs and other signatures for horizontal transfer, suggests that niche adaptation via organohalide respiration is a fundamental ecological strategy in Dehalococccoides. This adaptation has been exacted through multiple mechanisms of recombination that are mainly confined within HPRs of an otherwise remarkably stable, syntenic, streamlined genome among the smallest of any free-living microorganism