Vibrant times for mechanical metamaterials

Metamaterials are man-made designer matter that obtains its unusual effective properties by structure rather than chemistry. Building upon the success of electromagnetic and acoustic metamaterials, researchers working on mechanical metamaterials strive at obtaining extraordinary or extreme elasticity tensors and mass-density tensors to thereby mold static stress fields or the flow of longitudinal/transverse elastic vibrations in unprecedented ways. In this prospective paper, we focus on recent advances and remaining challenges in this emerging field. Examples are ultralight-weight, negative mass density, negative modulus, pentamode, anisotropic mass density, Origami, nonlinear, bistable, and reprogrammable mechanical metamaterials

Towards Error Handling in a DSL for Robot Assembly Tasks

This work-in-progress paper presents our work with a domain specific language (DSL) for tackling the issue of programming robots for small-sized batch production. We observe that as the complexity of assembly increases so does the likelihood of errors, and these errors need to be addressed. Nevertheless, it is essential that programming and setting up the assembly remains fast, allows quick changeovers, easy adjustments and reconfigurations. In this paper we present an initial design and implementation of extending an existing DSL for assembly operations with error specification, error handling and advanced move commands incorporating error tolerance. The DSL is used as part of a framework that aims at tackling uncertainties through a probabilistic approach.Comment: Presented at DSLRob 2014 (arXiv:cs/1411.7148

Continuous Constant-Memory Monitoring of Embedded Software Timing

Abstract-A method is presented for generating statistical models of timing data continuously over very long monitoring sessions. This method is intended for memory-efficient runtime modeling of timing properties in embedded software systems, such as execution times or inter-arrival times, but is a quite generic method that should be applicable for other purposes and domains as well. Specifically, we intend to use this method as a component in automatic generation of simulation models for probabilistic timing analysis of complex embedded software systems. Given a stream of data as input, this method gradually builds up a statistical model capturing the approximate distribution of the data. The method uses a modest and fixed amount of on-target RAM, decided by the desired accuracy of the model, and allows for long monitoring sessions covering billions of data points. The paper presents the motivation, algorithm, a prototype implementation and evaluation using real execution time data from an ARM7 microcontroller

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.Peer reviewe