TY - JOUR AB - Passivation layers on electrode materials are ubiquitous in nonaqueous battery chemistries and strongly govern performance and lifetime. They comprise breakdown products of the electrolyte including carbonate, alkyl carbonates, alkoxides, carboxylates, and polymers. Parasitic chemistry in metal–O2 batteries forms similar products and is tied to the deviation of the O2 balance from the ideal stoichiometry during formation/decomposition of alkaline peroxides or superoxides. Accurate and integral quantification of carbonaceous species and peroxides or superoxides in battery electrodes remains, however, elusive. We present a refined procedure to quantify them accurately and sensitively by pointing out and rectifying pitfalls of previous procedures. Carbonaceous compounds are differentiated into inorganic and organic ones. We combine mass and UV–vis spectrometry to quantify evolved O2 and complexed peroxide and CO2 evolved from carbonaceous compounds by acid treatment and Fenton’s reaction. The capabilities of the method are exemplified by means of Li–O2 and Na–O2 cathodes, graphite anodes, and LiNi0.8Co0.15Al0.05O2 cathodes. AU - Schafzahl, Bettina AU - Mourad, Eléonore AU - Schafzahl, Lukas AU - Petit, Yann K. AU - Raju, Anjana R. AU - Thotiyl, Musthafa Ottakam AU - Wilkening, Martin AU - Slugovc, Christian AU - Freunberger, Stefan Alexander ID - 7287 IS - 1 JF - ACS Energy Letters SN - 2380-8195 TI - Quantifying total superoxide, peroxide, and carbonaceous compounds in metal–O2 batteries and the solid electrolyte interphase VL - 3 ER - TY - JOUR AB - Hydrogelation, the self-assembly of molecules into soft, water-loaded networks, is one way to bridge the structural gap between single molecules and functional materials. The potential of hydrogels, such as those based on perylene bisimides, lies in their chemical, physical, optical, and electronic properties, which are governed by the supramolecular structure of the gel. However, the structural motifs and their precise role for long-range conductivity are yet to be explored. Here, we present a comprehensive structural picture of a perylene bisimide hydrogel, suggesting that its long-range conductivity is limited by charge transfer between electronic backbones. We reveal nanocrystalline ribbon-like structures as the electronic and structural backbone units between which charge transfer is mediated by polar solvent bridges. We exemplify this effect with sensing, where exposure to polar vapor enhances conductivity by 5 orders of magnitude, emphasizing the crucial role of the interplay between structural motif and surrounding medium for the rational design of devices based on nanocrystalline hydrogels. AU - Burian, Max AU - Rigodanza, Francesco AU - Demitri, Nicola AU - D̵ord̵ević, Luka AU - Marchesan, Silvia AU - Steinhartova, Tereza AU - Letofsky-Papst, Ilse AU - Khalakhan, Ivan AU - Mourad, Eléonore AU - Freunberger, Stefan Alexander AU - Amenitsch, Heinz AU - Prato, Maurizio AU - Syrgiannis, Zois ID - 7285 IS - 6 JF - ACS Nano SN - 1936-0851 TI - Inter-backbone charge transfer as prerequisite for long-range conductivity in perylene bisimide hydrogels VL - 12 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 - 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 - 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 - 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 - TY - JOUR AB - The availability of genome-wide genetic data on hundreds of thousands of people has led to an equally rapid growth in methodologies available to analyse these data. While the motivation for undertaking genome-wide association studies (GWAS) is identification of genetic markers associated with complex traits, once generated these data can be used for many other analyses. GWAS have demonstrated that complex traits exhibit a highly polygenic genetic architecture, often with shared genetic risk factors across traits. New methods to analyse data from GWAS are increasingly being used to address a diverse set of questions about the aetiology of complex traits and diseases, including psychiatric disorders. Here, we give an overview of some of these methods and present examples of how they have contributed to our understanding of psychiatric disorders. We consider: (i) estimation of the extent of genetic influence on traits, (ii) uncovering of shared genetic control between traits, (iii) predictions of genetic risk for individuals, (iv) uncovering of causal relationships between traits, (v) identifying causal single-nucleotide polymorphisms and genes or (vi) the detection of genetic heterogeneity. This classification helps organise the large number of recently developed methods, although some could be placed in more than one category. While some methods require GWAS data on individual people, others simply use GWAS summary statistics data, allowing novel well-powered analyses to be conducted at a low computational burden. AU - Maier, R. M. AU - Visscher, P. M. AU - Robinson, Matthew Richard AU - Wray, N. R. ID - 7721 IS - 7 JF - Psychological Medicine SN - 0033-2917 TI - Embracing polygenicity: A review of methods and tools for psychiatric genetics research VL - 48 ER - TY - JOUR AB - Creating a selective gel that filters particles based on their interactions is a major goal of nanotechnology, with far-reaching implications from drug delivery to controlling assembly pathways. However, this is particularly difficult when the particles are larger than the gel’s characteristic mesh size because such particles cannot passively pass through the gel. Thus, filtering requires the interacting particles to transiently reorganize the gel’s internal structure. While significant advances, e.g., in DNA engineering, have enabled the design of nano-materials with programmable interactions, it is not clear what physical principles such a designer gel could exploit to achieve selective permeability. We present an equilibrium mechanism where crosslink binding dynamics are affected by interacting particles such that particle diffusion is enhanced. In addition to revealing specific design rules for manufacturing selective gels, our results have the potential to explain the origin of selective permeability in certain biological materials, including the nuclear pore complex. AU - Goodrich, Carl Peter AU - Brenner, Michael P. AU - Ribbeck, Katharina ID - 7754 JF - Nature Communications SN - 2041-1723 TI - Enhanced diffusion by binding to the crosslinks of a polymer gel VL - 9 ER -