Radioactive Decay Studies of Nuclei Produced from Bombardment by Intermediate Energy Neutrons

This work was supported by National Science Foundation Grants PHY 76-84033A01, PHY 78-22774, and Indiana Universit

Flexizyme-Enabled Benchtop Biosynthesis of Thiopeptides

Thiopeptides are natural antibiotics that are fashioned from short peptides by multiple layers of post-translational modification. Their biosynthesis, in particular the pyridine synthases that form the macrocyclic antibiotic core, has attracted intensive research but is complicated by the challenges of reconstituting multiple-pathway enzymes. By combining select RiPP enzymes with cell free expression and flexizyme-based codon reprogramming, we have developed a benchtop biosynthesis of thiopeptide scaffolds. This strategy side-steps several challenges related to the investigation of thiopeptide enzymes and allows access to analytical quantities of new thiopeptide analogs. We further demonstrate that this strategy can be used to validate the activity of new pyridine synthases without the need to reconstitute the cognate prior pathway enzymes

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update

Personalised Therapeutic

From thermal rectifiers to thermoelectric devices

We discuss thermal rectification and thermoelectric energy conversion from the perspective of nonequilibrium statistical mechanics and dynamical systems theory. After preliminary considerations on the dynamical foundations of the phenomenological Fourier law in classical and quantum mechanics, we illustrate ways to control the phononic heat flow and design thermal diodes. Finally, we consider the coupled transport of heat and charge and discuss several general mechanisms for optimizing the figure of merit of thermoelectric efficiency.Comment: 42 pages, 22 figures, review paper, to appear in the Springer Lecture Notes in Physics volume "Thermal transport in low dimensions: from statistical physics to nanoscale heat transfer" (S. Lepri ed.

Next-to-Leading Order QCD Analysis of Polarized Deep Inelastic Scattering Data

We present a Next-to-Leading order perturbative QCD analysis of world data on the spin dependent structure functions $g_1^p, g_1^n$, and $g_1^d$, including the new experimental information on the $Q^2$ dependence of $g_1^n$. Careful attention is paid to the experimental and theoretical uncertainties. The data constrain the first moments of the polarized valence quark distributions, but only qualitatively constrain the polarized sea quark and gluon distributions. The NLO results are used to determine the $Q^2$ dependence of the ratio $g_1/F_1$ and evolve the experimental data to a constant $Q^2 = 5 GeV^2$. We determine the first moments of the polarized structure functions of the proton and neutron and find agreement with the Bjorken sum rule.Comment: 21 pages, 4 figures; final version to be published in Phys. Lett. B. References updated. Uses elsart.cls version 1996/04/22, 2e-1.4

Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Social–environmental drivers inform strategic management of coral reefs in the Anthropocene

Without drastic efforts to reduce carbon emissions and mitigate globalized stressors, tropical coral reefs are in jeopardy. Strategic conservation and management requires identification of the environmental and socioeconomic factors driving the persistence of scleractinian coral assemblages—the foundation species of coral reef ecosystems. Here, we compiled coral abundance data from 2,584 Indo-Pacific reefs to evaluate the influence of 21 climate, social and environmental drivers on the ecology of reef coral assemblages. Higher abundances of framework-building corals were typically associated with: weaker thermal disturbances and longer intervals for potential recovery; slower human population growth; reduced access by human settlements and markets; and less nearby agriculture. We therefore propose a framework of three management strategies (protect, recover or transform) by considering: (1) if reefs were above or below a proposed threshold of >10% cover of the coral taxa important for structural complexity and carbonate production; and (2) reef exposure to severe thermal stress during the 2014–2017 global coral bleaching event. Our findings can guide urgent management efforts for coral reefs, by identifying key threats across multiple scales and strategic policy priorities that might sustain a network of functioning reefs in the Indo-Pacific to avoid ecosystem collapse

Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe