Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization

IN SITU X-RAY ABSORPTION SPECTROSCOPY STUDY OF TIN ANODE NANOMATERIALS FOR LITHIUM-ION BATTERIES

Tin is an attractive alternative to replace traditional carbon based anodes in lithium-ion batteries (LIBs) due to the nearly three-fold increase in theoretical capacity over carbon. However, metallic tin su↵ers from volumetric expansion of the crystal structure during initial lithium insertion that quickly degrades the material and reduces the performance of the battery. Various techniques have been previously investigated with the goal of suppressing this destructive expansion by incorporating oxygen or a lithium-inactive metal into the tin to provide structural support and mitigate volumetric expansion. These materials show increased capacity retention compared to metallic tin, but still su↵er from capacity fading. The nature of these structural degradations must be fully understood to permit engineering of materials that avoid these destructive tendencies and can be considered as viable options for LIBs. In situ X-ray absorption spectroscopy (XAS) measurements were acquired on Sn, SnO2, Sn3 O2(OH)2, Cu6Sn5 and Ni3Sn4 nanoparticle anodes for LIBs. Accompanying the electrochemical characterization conducted on each material, the local atomic structure was modeled as a function of potential during the first charge and also as a function of charged/discharged states for several cycles. The extended X-ray absorption fine structure (EXAFS) theoretical modeling included the first unambiguous observation of Sn-Li coordination numbers and atomic distances in tin-based anode materials. From correlating the electrochemical performance to the EXAFS analysis, the long-term capacity retention of tin-based anodes is dependent on the structural deformations that occur during the first charge. The conversion of oxygen to amorphous Li2O, and the network that it forms, has a dramatic e↵ect on the kinetics of the system and the stability of the local metallic tin structure.Ph.D. in Physics, May 201

In Situ X‑ray Absorption Spectroscopy Study of the Capacity Fading Mechanism in Hybrid Sn₃O₂(OH)₂/Graphite Battery Anode Nanomaterials

In situ X-ray absorption spectroscopy (XAS) of an electrode material under electrochemical control has enabled a detailed examination of the capacity fading mechanism during charge–discharge cycling in a hybrid nanomaterial, Sn₃O₂(OH)₂/graphite, that is considered for use as a high-capacity lithium-ion battery anode. By the use of an original one-pot solvothermal synthesis technique, Sn₃O₂(OH)₂ nanoparticles were directly deposited on the surface of nanothin graphite and were charged/discharged in situ for several cycles while XAS spectra at the Sn K-edge were taken. Modeling of the collected extended X-ray absorption fine structure (EXAFS) spectra provides detailed information on the Sn–O, Sn–Sn, and Sn–Li coordination numbers and atomic distances for each charged and discharged electrode state. On the basis of electrochemical data and the changes in atomic arrangement deduced from the EXAFS fitting results, including the first unambiguous observation of Sn–Li near neighbors, a capacity fading mechanism is proposed that is different from widely accepted volume expansion for tin metal and tin oxides. Our experimental results suggest that atomic clusters of metallic tin surrounded by highly disordered Li₂O shells are formed on first charge. The metallic tin clusters participate in lithiation and delithiation on the following charge/discharge cycles; however, because of continued segregation of tin and Li₂O phases, the tin clusters eventually lose electrical contact with the rest of the electrode and become excluded from further participation in electrochemical reactions, resulting in reduced capacity of this anode material

Potential-Resolved In Situ X‑ray Absorption Spectroscopy Study of Sn and SnO₂ Nanomaterial Anodes for Lithium-Ion Batteries

This work provides detailed analysis of processes occurring in metallic Sn and SnO₂ anode materials for lithium ion batteries during first lithiation, studied in situ with rapid continuous X-ray absorption spectroscopy (XAS). The X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectra provide information on dynamic changes in the Sn atomic environment, including type and number of neighboring atoms and interatomic distances. A unique methodology was used to model insertion of Li atoms into the electrode material structure and to analyze the formation of SnLi phases within the electrodes. Additionally, analysis of fully lithiated and delithiated states of Sn and SnO₂ electrodes in the first two cycles provides insight into the reasons for poor electrochemical performance and rapid capacity decline. Results indicate that use of SnO₂ is more promising than metallic Sn as an anode material, but more effort in nanoscale and atomic engineering of anodes is required for commercially feasible use of Sn-based materials

In Situ Ru K‑Edge X‑ray Absorption Spectroscopy Study of Methanol Oxidation Mechanisms on Model Submonolayer Ru on Pt Nanoparticle Electrocatalyst

In situ X-ray absorption spectroscopy (XAS) with electrochemical reaction control has enabled a detailed investigation of the mechanism of the methanol electrooxidation by a bimetallic PtRu catalyst. By the use of an original electrodeposition technique, ca. 0.3 monolayer of Ru was deposited on the surface of unsupported Pt nanoparticles (Ru@Pt). The presence of Ru atoms only at the surface of nanoparticles turns a bulk sensitive XAS technique into a surface methodology which permits correlation of the X-ray absorption fine structure at the Ru K-edge to the role of Ru atoms in the methanol oxidation process. In situ XAS spectra of the Ru@Pt nanoparticles were collected at various electrode potentials in background electrolyte, and then in 1 M solution of methanol (CH₃OH) in the same electrolyte. Significant differences in the catalyst state have been revealed between these two environments. In the background electrolyte, Ru gradually oxidizes from mostly metallic to a Ru­(III)/Ru­(IV) mixture at the highest potentials. In the presence of CH₃OH, the Ru oxidation state remains a mixture of metallic and Ru­(III) even at the highest potentials. CO-type species were found adsorbed on Ru atoms at all potentials and coadsorbed with OH species at potentials 0.175 V vs Ag/AgCl and higher with steady number of near neighbors. The same potential correlates to the beginning of methanol oxidation reaction observed electrochemically. Therefore coadsorption of CO and OH groups on Ru atoms appears to be critical in the methanol oxidation process. The need for OH groups for CO removal from Pt sites was previously suggested by the bifunctional CH₃OH oxidation mechanism; however, occupancy of Ru atoms with CO species and direct structural observations of the coadsorption of CO and OH on the same Ru atom is a novel finding resulting from this study. Other changes in the catalyst environment were observed, including decreased Ru–Ru and Ru–Pt bond distances, increased numbers of Ru–Pt near neighbors, and decreased number of Ru–Ru near neighbors

Surface Modification Approach to TiO₂ Nanofluids with High Particle Concentration, Low Viscosity, and Electrochemical Activity

This study presents a new approach to the formulation of functional nanofluids with high solid loading and low viscosity while retaining the surface activity of nanoparticles, in particular, their electrochemical response. The proposed methodology can be applied to a variety of functional nanomaterials and enables exploration of nanofluids as a medium for industrial applications beyond heat transfer fluids, taking advantage of both liquid behavior and functionality of dispersed nanoparticles. The highest particle concentration achievable with pristine 25 nm titania (TiO₂) nanoparticles in aqueous electrolytes (pH 11) is 20 wt %, which is limited by particle aggregation and high viscosity. We have developed a scalable one-step surface modification procedure for functionalizing those TiO₂ nanoparticles with a monolayer coverage of propyl sulfonate groups, which provides steric and charge-based separation of particles in suspension. Stable nanofluids with TiO₂ loadings up to 50 wt % and low viscosity are successfully prepared from surface-modified TiO₂ nanoparticles in the same electrolytes. Viscosity and thermal conductivity of the resulting nanofluids are evaluated and compared to nanofluids prepared from pristine nanoparticles. Furthermore, it is demonstrated that the surface-modified titania nanoparticles retain more than 78% of their electrochemical response as compared to that of the pristine material. Potential applications of the proposed nanofluids include, but are not limited to, electrochemical energy storage and catalysis, including photo- and electrocatalysis

Probing the Li Insertion Mechanism of ZnFe₂O₄ in Li-Ion Batteries: A Combined X‑Ray Diffraction, Extended X‑Ray Absorption Fine Structure, and Density Functional Theory Study

We report an extensive study on fundamental properties that determine the functional electrochemistry of ZnFe₂O₄ spinel (theoretical capacity of 1000 mAh/g). For the first time, the reduction mechanism is followed through a combination of in situ X-ray diffraction data, synchrotron based powder diffraction, and ex-situ extended X-ray absorption fine structure allowing complete visualization of reduction products irrespective of their crystallinity. The first 0.5 electron equivalents (ee) do not significantly change the starting crystal structure. Subsequent lithiation results in migration of Zn²⁺ ions from 8a tetrahedral sites into vacant 16c sites. Density functional theory shows that Li⁺ ions insert into 16c site initially and then 8a site with further lithiation. Fe metal is formed over the next eight ee of reduction with no evidence of concurrent Zn²⁺ reduction to Zn metal. Despite the expected formation of LiZn alloy from the electron count, we find no evidence for this phase under the tested conditions. Additionally, upon oxidation to 3 V, we observe an FeO phase with no evidence of Fe₂O₃. Electrochemistry data show higher electron equivalent transfer than can be accounted for solely based on ZnFe₂O₄ reduction indicating excess capacity ascribed to carbon reduction or surface electrolyte interphase formation

Dispersion of Nanocrystalline Fe₃O₄ within Composite Electrodes: Insights on Battery-Related Electrochemistry

Aggregation of nanosized materials in composite lithium-ion-battery electrodes can be a significant factor influencing electrochemical behavior. In this study, aggregation was controlled in magnetite, Fe₃O₄, composite electrodes via oleic acid capping and subsequent dispersion in a carbon black matrix. A heat treatment process was effective in the removal of the oleic acid capping agent while preserving a high degree of Fe₃O₄ dispersion. Electrochemical testing showed that Fe₃O₄ dispersion is initially beneficial in delivering a higher functional capacity, in agreement with continuum model simulations. However, increased capacity fade upon extended cycling was observed for the dispersed Fe₃O₄ composites relative to the aggregated Fe₃O₄ composites. X-ray absorption spectroscopy measurements of electrodes post cycling indicated that the dispersed Fe₃O₄ electrodes are more oxidized in the discharged state, consistent with reduced reversibility compared with the aggregated sample. Higher charge-transfer resistance for the dispersed sample after cycling suggests increased surface-film formation on the dispersed, high-surface-area nanocrystalline Fe₃O₄ compared to the aggregated materials. This study provides insight into the specific effects of aggregation on electrochemistry through a multiscale view of mechanisms for magnetite composite electrodes