Pattern formation in stiff oscillatory media with nonlocal coupling: A numerical study of the hydrogen oxidation reaction on Pt electrodes in the presence of poisons

The impact of the strength of negative (desynchronizing) global coupling (NGC) on the spatiotemporal dynamics of an electrochemical relaxation oscillator is studied numerically with a prototypical model, the electro-oxidation of hydrogen in the presence of poisons. The results are compared with recent experiments. The NGC has a destabilizing effect on the homogeneous oscillations. Both, in theory and in experiments, the basic patterns found with increasing global coupling strength are modulated oscillations, target patterns (including an asymmetric variant), and modulated pulses, the average spatial inhomogeneity during an oscillation increasing with the intensity of the NGC. It is suggested that this scenario is typical for strong relaxation oscillations, and a comparison with an electrochemical oscillator exhibiting harmonic oscillations points to the fact that the critical coupling strength, upon which the complete synchronization is destroyed, is larger for relaxation oscillations than for harmonic oscillations. In addition, the numerical simulations predicted two- and three-phase cluster patterns at high coupling strength. Also in experiments cluster patterns were observed, however only in parameter regions of the local dynamics which were different from the one investigated in this study

Results of four years of digital urban monitoring of Rattus norvegicus with RatMap in Hamburg including data on infestation near the surface and in underground sewers

Plenge-Bönig, A., Zickert, A., Baumgardt, K., Sammann, A

Following Paths of Maximum Catalytic Activity in the Composition Space of High‐Entropy Alloys

The search for better and cheaper electrocatalysts is vital in the global transition to renewable energy resources. High-entropy alloys (HEAs) provide a near-infinite number of different alloys with approximately continuous properties such as catalytic activity. In this work, the catalytic activity for the electrochemical oxygen reduction reaction as a function of molar composition of Ag-Ir-Pd-Pt-Ru HEA is treated as a landscape wherein it is shown that the maxima are connected through ridges. By following the ridges, it is possible to navigate between the maxima using a modified nudged elastic band (NEB) model integrated in a machine learning NEB algorithm. These results provide a new understanding of the composition space being similar to an evolutionary landscape. This provides a possible new search and design strategy for new catalysts in which the composition of known catalysts can be optimized by following ridges rather than exploring the whole alloy composition space

Identification of the NF-κB activating protein-like locus as a risk locus for rheumatoid arthritis

Objective: To fine-map the NF-κB activating protein-like (NKAPL) locus identified in a prior genome-wide study as a possible rheumatoid arthritis (RA) risk locus and thereby delineate additional variants with stronger and/or independent disease association. Methods: Genotypes for 101 SNPs across the NKAPL locus on chromosome 6p22.1 were obtained on 1368 Canadian RA cases and 1471 controls. Single marker associations were examined using logistic regression and the most strongly associated NKAPL locus SNPs then typed in another Canadian and a US-based RA case/control cohort. Results: Fine-mapping analyses identified six NKAPL locus variants in a single haplotype block showing association with p≤5.6×10−8 in the combined Canadian cohort. Among these SNPs, rs35656932 in the zinc finger 193 gene and rs13208096 in the NKAPL gene remained significant after conditional logistic regression, contributed independently to risk for disease, and were replicated in the US cohort (Pcomb=4.24×10−10 and 2.44×10−9, respectively). These associations remained significant after conditioning on SNPs tagging the HLA-shared epitope (SE) DRB1*0401 allele and were significantly stronger in the HLA-SE negative versus positive subgroup, with a significant negative interaction apparent between HLA-DRB1 SE and NKAPL risk alleles. Conclusions: By illuminating additional NKAPL variants with highly significant effects on risk that are distinct from, but interactive with those arising from the HLA-DRB1 locus, our data conclusively identify NKAPL as an RA susceptibility locus

TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits

Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21)), A928V (rs35018800, OR = 0.53, P = 1.2 x 10(-9)), and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7)). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6 x 10(-18)), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; P(omnibus) = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing \u3e500 phenotypes using electronic medical records (EMR) in \u3e29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases

Analysis and Application of European Genetic Substructure Using 300 K SNP Information

European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans

Data for Genetic Analysis Workshop 16 Problem 1, Association Analysis of Rheumatoid Arthritis Data

For Genetic Analysis Workshop 16 Problem 1, we provided data for genome-wide association analysis of rheumatoid arthritis. Single-nucleotide polymorphism (SNP) genotype data were provided for 868 cases and 1194 controls that had been assayed using an Illumina 550 k platform. In addition, phenotypic data were provided from genotyping DRB1 alleles, which were classified according to the rheumatoid arthritis shared epitope, levels of anti-cyclic citrullinated peptide, and levels of rheumatoid factor IgM. Several questions could be addressed using the data, including analysis of genetic associations using single SNPs or haplotypes, as well as gene-gene and genetic analysis of SNPs for qualitative and quantitative factors