TY - JOUR AB - The solid electrolyte interphase (SEI) in Li and Na ion batteries forms when highly reducing or oxidizing electrode materials come into contact with a liquid organic electrolyte. Its ability to form a mechanically robust, ion-conducting, and electron-insulating layer critically determines performance, cycle life, and safety. Li or Na alkyl carbonates (LiAC and NaAC, respectively) are lead SEI components in state-of-the-art carbonate based electrolytes, and our fundamental understanding of their charge transport and mechanical properties may hold the key to designing electrolytes forming an improved SEI. We synthesized a homologous series of LiACs and NaACs from methyl to octyl analogues and characterized them with respect to structure, ionic conductivity, and stiffness. The compounds assume layered structures except for the lithium methyl carbonate. Room-temperature conductivities were found to be ∼10–9 S cm–1 for lithium methyl carbonate, <10–12 S cm–1 for the other LiACs, and <10–12 S cm–1 for the NaACs with ion transport mostly attributed to grain boundaries. While LiACs show stiffnesses of ∼1 GPa, NaACs become significantly softer with increasing chain lengths. These findings will help to more precisely interpret the complex results from charge transport and mechanical characterization of real SEIs and can give a rationale for influencing the SEI’s mechanical properties via the electrolyte. AU - Schafzahl, Lukas AU - Ehmann, Heike AU - Kriechbaum, Manfred AU - Sattelkow, Jürgen AU - Ganner, Thomas AU - Plank, Harald AU - Wilkening, Martin AU - Freunberger, Stefan Alexander ID - 7286 IS - 10 JF - Chemistry of Materials SN - 0897-4756 TI - Long-chain Li and Na alkyl carbonates as solid electrolyte interphase components: Structure, ion transport, and mechanical properties VL - 30 ER - TY - CONF AB - Proofs of space (PoS) [Dziembowski et al., CRYPTO'15] are proof systems where a prover can convince a verifier that he "wastes" disk space. PoS were introduced as a more ecological and economical replacement for proofs of work which are currently used to secure blockchains like Bitcoin. In this work we investigate extensions of PoS which allow the prover to embed useful data into the dedicated space, which later can be recovered. Our first contribution is a security proof for the original PoS from CRYPTO'15 in the random oracle model (the original proof only applied to a restricted class of adversaries which can store a subset of the data an honest prover would store). When this PoS is instantiated with recent constructions of maximally depth robust graphs, our proof implies basically optimal security. As a second contribution we show three different extensions of this PoS where useful data can be embedded into the space required by the prover. Our security proof for the PoS extends (non-trivially) to these constructions. We discuss how some of these variants can be used as proofs of catalytic space (PoCS), a notion we put forward in this work, and which basically is a PoS where most of the space required by the prover can be used to backup useful data. Finally we discuss how one of the extensions is a candidate construction for a proof of replication (PoR), a proof system recently suggested in the Filecoin whitepaper. AU - Pietrzak, Krzysztof Z ID - 7407 SN - 1868-8969 T2 - 10th Innovations in Theoretical Computer Science Conference (ITCS 2019) TI - Proofs of catalytic space VL - 124 ER - TY - JOUR AB - The coupling between magnetic and electric subsystems in composites of ferromagnetic and ferroelectric phases is a product property that is facilitated by mechanical strain that arises due to magnetostriction and the piezoelectric effect in the constituent phases. Such multiferroic composites are of immense interests for studies on the physics of electromagnetic coupling and for use in a variety of applications. Here, we focus on magneto-electric (ME) coupling in nanocomposites. Particular emphasis is on core-shell particles and coaxial fibers, thin film heterostructures, and planar structures with a variety of mechanical connectivity. A brief review of models that predict strong ME effects in nanostructures is followed by synthesis and characterization. Core-shell particulate composites can be prepared by hydrothermal processes and chemical or deoxyribonucleic acid-assisted assembly. Electrospinning techniques have been utilized to prepare defect free core-shell nanofibers. Core-shell particles and fibers can be assembled into superstructures with the aid of magnetic and electric fields and characterized for possible use in advanced technologies. Chemical-vapor deposition techniques have been shown to be effective for the preparation of heterostructures of ferrites and ferroelectrics. Exotic planar multiferroic structures with potential for enhancing ME coupling strengths are also considered. Scanning probe microscopy techniques are ideal for probing the nature of direct- and converse-ME coupling in individual nanostructures. Magnetoelectric characterization of assemblies of nanocomposites can be done by ME voltage coefficient, magnetic field induced polarization, and magneto-dielectric effects. We conclude with a brief discussion on possible avenues for strengthening the product properties in the nanocomposites. AU - Viehland, Dwight AU - Li, Jie Fang AU - Yang, Yaodong AU - Costanzo, Tommaso AU - Yourdkhani, Amin AU - Caruntu, Gabriel AU - Zhou, Peng AU - Zhang, Tianjin AU - Li, Tianqian AU - Gupta, Arunava AU - Popov, Maksym AU - Srinivasan, Gopalan ID - 7458 IS - 6 JF - Journal of Applied Physics SN - 0021-8979 TI - Tutorial: Product properties in multiferroic nanocomposites VL - 124 ER - TY - JOUR AB - Background: DNA methylation levels change along with age, but few studies have examined the variation in the rate of such changes between individuals. Methods: We performed a longitudinal analysis to quantify the variation in the rate of change of DNA methylation between individuals using whole blood DNA methylation array profiles collected at 2–4 time points (N = 2894) in 954 individuals (67–90 years). Results: After stringent quality control, we identified 1507 DNA methylation CpG sites (rsCpGs) with statistically significant variation in the rate of change (random slope) of DNA methylation among individuals in a mixed linear model analysis. Genes in the vicinity of these rsCpGs were found to be enriched in Homeobox transcription factors and the Wnt signalling pathway, both of which are related to ageing processes. Furthermore, we investigated the SNP effect on the random slope. We found that 4 out of 1507 rsCpGs had one significant (P < 5 × 10−8/1507) SNP effect and 343 rsCpGs had at least one SNP effect (436 SNP-probe pairs) reaching genome-wide significance (P < 5 × 10−8). Ninety-five percent of the significant (P < 5 × 10−8) SNPs are on different chromosomes from their corresponding probes. Conclusions: We identified CpG sites that have variability in the rate of change of DNA methylation between individuals, and our results suggest a genetic basis of this variation. Genes around these CpG sites have been reported to be involved in the ageing process. AU - Zhang, Qian AU - Marioni, Riccardo E AU - Robinson, Matthew Richard AU - Higham, Jon AU - Sproul, Duncan AU - Wray, Naomi R AU - Deary, Ian J AU - McRae, Allan F AU - Visscher, Peter M ID - 7717 IS - 1 JF - Genome Medicine SN - 1756-994X TI - Genotype effects contribute to variation in longitudinal methylome patterns in older people VL - 10 ER - TY - JOUR AB - Flores Island, Indonesia, was inhabited by the small-bodied hominin species Homo floresiensis, which has an unknown evolutionary relationship to modern humans. This island is also home to an extant human pygmy population. Here we describe genome-scale single-nucleotide polymorphism data and whole-genome sequences from a contemporary human pygmy population living on Flores near the cave where H. floresiensis was found. The genomes of Flores pygmies reveal a complex history of admixture with Denisovans and Neanderthals but no evidence for gene flow with other archaic hominins. Modern individuals bear the signatures of recent positive selection encompassing the FADS (fatty acid desaturase) gene cluster, likely related to diet, and polygenic selection acting on standing variation that contributed to their short-stature phenotype. Thus, multiple independent instances of hominin insular dwarfism occurred on Flores. AU - Tucci, Serena AU - Vohr, Samuel H. AU - McCoy, Rajiv C. AU - Vernot, Benjamin AU - Robinson, Matthew Richard AU - Barbieri, Chiara AU - Nelson, Brad J. AU - Fu, Wenqing AU - Purnomo, Gludhug A. AU - Sudoyo, Herawati AU - Eichler, Evan E. AU - Barbujani, Guido AU - Visscher, Peter M. AU - Akey, Joshua M. AU - Green, Richard E. ID - 7718 IS - 6401 JF - Science SN - 0036-8075 TI - Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia VL - 361 ER - TY - JOUR AB - Male pattern baldness (MPB) is a sex-limited, age-related, complex trait. We study MPB genetics in 205,327 European males from the UK Biobank. Here we show that MPB is strongly heritable and polygenic, with pedigree-heritability of 0.62 (SE = 0.03) estimated from close relatives, and SNP-heritability of 0.39 (SE = 0.01) from conventionally-unrelated males. We detect 624 near-independent genome-wide loci, contributing SNP-heritability of 0.25 (SE = 0.01), of which 26 X-chromosome loci explain 11.6%. Autosomal genetic variance is enriched for common variants and regions of lower linkage disequilibrium. We identify plausible genetic correlations between MPB and multiple sex-limited markers of earlier puberty, increased bone mineral density (rg = 0.15) and pancreatic β-cell function (rg = 0.12). Correlations with reproductive traits imply an effect on fitness, consistent with an estimated linear selection gradient of -0.018 per MPB standard deviation. Overall, we provide genetic insights into MPB: a phenotype of interest in its own right, with value as a model sex-limited, complex trait. AU - Yap, Chloe X. AU - Sidorenko, Julia AU - Wu, Yang AU - Kemper, Kathryn E. AU - Yang, Jian AU - Wray, Naomi R. AU - Robinson, Matthew Richard AU - Visscher, Peter M. ID - 7712 JF - Nature Communications SN - 2041-1723 TI - Dissection of genetic variation and evidence for pleiotropy in male pattern baldness VL - 9 ER - TY - JOUR AB - Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. AU - Maier, Robert M. AU - Zhu, Zhihong AU - Lee, Sang Hong AU - Trzaskowski, Maciej AU - Ruderfer, Douglas M. AU - Stahl, Eli A. AU - Ripke, Stephan AU - Wray, Naomi R. AU - Yang, Jian AU - Visscher, Peter M. AU - Robinson, Matthew Richard ID - 7716 JF - Nature Communications SN - 2041-1723 TI - Improving genetic prediction by leveraging genetic correlations among human diseases and traits VL - 9 ER - TY - JOUR AB - Preference for mates with similar phenotypes; that is, assortative mating, is widely observed in humans1,2,3,4,5 and has evolutionary consequences6,7,8. Under Fisher's classical theory6, assortative mating is predicted to induce a signature in the genome at trait-associated loci that can be detected and quantified. Here, we develop and apply a method to quantify assortative mating on a specific trait by estimating the correlation (θ) between genetic predictors of the trait from single nucleotide polymorphisms on odd- versus even-numbered chromosomes. We show by theory and simulation that the effect of assortative mating can be quantified in the presence of population stratification. We applied this approach to 32 complex traits and diseases using single nucleotide polymorphism data from ~400,000 unrelated individuals of European ancestry. We found significant evidence of assortative mating for height (θ = 3.2%) and educational attainment (θ = 2.7%), both of which were consistent with theoretical predictions. Overall, our results imply that assortative mating involves multiple traits and affects the genomic architecture of loci that are associated with these traits, and that the consequence of mate choice can be detected from a random sample of genomes. AU - Yengo, Loic AU - Robinson, Matthew Richard AU - Keller, Matthew C. AU - Kemper, Kathryn E. AU - Yang, Yuanhao AU - Trzaskowski, Maciej AU - Gratten, Jacob AU - Turley, Patrick AU - Cesarini, David AU - Benjamin, Daniel J. AU - Wray, Naomi R. AU - Goddard, Michael E. AU - Yang, Jian AU - Visscher, Peter M. ID - 7715 IS - 12 JF - Nature Human Behaviour SN - 2397-3374 TI - Imprint of assortative mating on the human genome VL - 2 ER - TY - JOUR AB - Health risk factors such as body mass index (BMI) and serum cholesterol are associated with many common diseases. It often remains unclear whether the risk factors are cause or consequence of disease, or whether the associations are the result of confounding. We develop and apply a method (called GSMR) that performs a multi-SNP Mendelian randomization analysis using summary-level data from genome-wide association studies to test the causal associations of BMI, waist-to-hip ratio, serum cholesterols, blood pressures, height, and years of schooling (EduYears) with common diseases (sample sizes of up to 405,072). We identify a number of causal associations including a protective effect of LDL-cholesterol against type-2 diabetes (T2D) that might explain the side effects of statins on T2D, a protective effect of EduYears against Alzheimer’s disease, and bidirectional associations with opposite effects (e.g., higher BMI increases the risk of T2D but the effect of T2D on BMI is negative). AU - Zhu, Zhihong AU - Zheng, Zhili AU - Zhang, Futao AU - Wu, Yang AU - Trzaskowski, Maciej AU - Maier, Robert AU - Robinson, Matthew Richard AU - McGrath, John J. AU - Visscher, Peter M. AU - Wray, Naomi R. AU - Yang, Jian ID - 7714 JF - Nature Communications SN - 2041-1723 TI - Causal associations between risk factors and common diseases inferred from GWAS summary data VL - 9 ER - TY - JOUR AB - There are mean differences in complex traits among global human populations. We hypothesize that part of the phenotypic differentiation is due to natural selection. To address this hypothesis, we assess the differentiation in allele frequencies of trait-associated SNPs among African, Eastern Asian, and European populations for ten complex traits using data of large sample size (up to ~405,000). We show that SNPs associated with height (P=2.46×10−5), waist-to-hip ratio (P=2.77×10−4), and schizophrenia (P=3.96×10−5) are significantly more differentiated among populations than matched “control” SNPs, suggesting that these trait-associated SNPs have undergone natural selection. We further find that SNPs associated with height (P=2.01×10−6) and schizophrenia (P=5.16×10−18) show significantly higher variance in linkage disequilibrium (LD) scores across populations than control SNPs. Our results support the hypothesis that natural selection has shaped the genetic differentiation of complex traits, such as height and schizophrenia, among worldwide populations. AU - Guo, Jing AU - Wu, Yang AU - Zhu, Zhihong AU - Zheng, Zhili AU - Trzaskowski, Maciej AU - Zeng, Jian AU - Robinson, Matthew Richard AU - Visscher, Peter M. AU - Yang, Jian ID - 7713 JF - Nature Communications SN - 2041-1723 TI - Global genetic differentiation of complex traits shaped by natural selection in humans VL - 9 ER -