A Computational Study of the Proton-Transfer Chemistry of the Silaformyl Anion

Proton-transfer reactions involving the silaformyl anion, HSiO-, and its conjugate acids, HSiOH and H2SiO, have been investigated with ab initio methods. Calculations through fourth-order perturbation theory suggest possible routes for proton transfer. Accurate estimates for the acidity of H2SiO and HSiOH are presented and discussed in light of earlier experimental estimates

Facile collection of two-dimensional electronic spectra using femtosecond pulse-shaping technology

This letter reports a straightforward means of collecting two-dimensional electronic (2D-E) spectra using optical tools common to many research groups involved in ultrafast spectroscopy and quantum control. In our method a femtosecond pulse shaper is used to generate a pair of phase stable collinear laser pulses which are then incident on a gas or liquid sample. The pulse pair is followed by an ultrashort probe pulse that is spectrally resolved. The delay between the collinear pulses is incremented using phase and amplitude shaping and a 2D-E spectrum is generated following Fourier transformation. The partially collinear beam geometry results in perfectly phased absorptive spectra without phase twist. Our approach is much simpler to implement than standard non-collinear beam geometries, which are challenging to phase stabilize and require complicated calibrations. Using pulse shaping, many new experiments are now also possible in both 2D-E spectroscopy and coherent control.open798

Ultrafast Time-Resolved Hard X-Ray Emission Spectroscopy on a Tabletop

Experimental tools capable of monitoring both atomic and electronic structure on ultrafast (femtosecond to picosecond) time scales are needed for investigating photophysical processes fundamental to light harvesting, photocatalysis, energy and data storage, and optical display technologies. Time-resolved hard x-ray (>3 keV) spectroscopies have proven valuable for these measurements due to their elemental specificity and sensitivity to geometric and electronic structures. Here, we present the first tabletop apparatus capable of performing time-resolved x-ray emission spectroscopy. The time resolution of the apparatus is better than 6 ps. By combining a compact laser-driven plasma source with a highly efficient array of microcalorimeter x-ray detectors, we are able to observe photoinduced spin changes in an archetypal polypyridyl iron complex ½Feð2; 20 -bipyridineÞ3 2þ and accurately measure the lifetime of the quintet spin state. Our results demonstrate that ultrafast hard x-ray emission spectroscopy is no longer confined to large facilities and now can be performed in conventional laboratories with 10 times better time resolution than at synchrotrons. Our results are enabled, in part, by a 100- to 1000-fold increase in x-ray collection efficiency compared to current techniques

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

A Computational Study of the Proton-Transfer Chemistry of the Silaformyl Anion

Proton-transfer reactions involving the silaformyl anion, HSiO-, and its conjugate acids, HSiOH and H2SiO, have been investigated with ab initio methods. Calculations through fourth-order perturbation theory suggest possible routes for proton transfer. Accurate estimates for the acidity of H2SiO and HSiOH are presented and discussed in light of earlier experimental estimates.Reprinted (adapted) with permission from Journal of the American Chemical Society 120 (1998): 2124, doi:10.1021/ja9722077. Copyright 1998 American Chemical Society.</p

Computational Studies of Carbodiimide Rings

Computational studies of alicyclic carbodiimides (RNCNR) (rings five through twelve) at the MP2/6-31G­(d,p)//MP2/6-31G­(d,p) level of theory were conducted to locate the transition states between carbodiimides isomers. Transition states for rings six through twelve were found. The RNCNR dihedral angle is ∼0° for even-numbered rings, but deviates from 0° for rings seven, nine, eleven, and twelve. The even- and odd-numbered ring transition states have different symmetry point groups. C_s transition states (even rings) have an imaginary frequency mode that transforms as the asymmetric irreducible representation of the group. C₂ transition states (odd rings) have a corresponding mode that transforms as the totally symmetric representation. Intrinsic reaction coordinate analyses followed by energy minimization along the antisymmetric pathways led to enantiomeric pairs. The symmetric pathways give diastereomeric isomers. The five-membered ring carbodiimide is a stable structure, possibly isolable. A twelve-membered ring transition state was found only without applying symmetry constraints (C₁). Molecular mechanics and molecular dynamics studies of the seven-, eight-, and nine-membered rings gave additional structures, which were then minimized using ab initio methods. No structures beyond those found from the IRC analyses described were found. The potential for optical resolution of the seven-membered ring is discussed