Peak effect in laser ablated DyBa2Cu3O7-d films at microwave frequencies at subcritical currents

In this paper we report the observation of a peak in the microwave surface resistance (at frequencies ~10GHz) of laser ablated DyBa2Cu3O7-d films in magnetic field ranging from 2 to 9kOe (||c) close to the superconducting transition temperature (Tc(H)). The exact nature of peak is sample dependent but it follows a general behaviour. The peak shifts to lower temperature when the magnetic field is increased. It has strong frequency dependence and the peak is pronounced at frequencies close to the depinning frequency of the flux line lattice. From the observed temperature and field dependence we argue that this peak is associated with the order disorder transition of the flux line lattice close to Tc(H).Comment: 8 pages, 2 pages (accepted for publication in JAP, Intermag symposium proceeding

Critical current of a superconductor measured via injection of spin polarized carriers

In this paper we report a direct evidence of the suppression of critical current due to pair-breaking in a superconducting micro-bridge when the measurement is carried out by injecting spin polarised carriers instead of normal electrons. A thin layer of La0.7Ca0.3MnO3 was used as the source of spin polarised carriers. The micro-bridge was formed on the DyBa2Cu3O7-d thin film by photo-lithographic techniques. The design of our spin-injection device allowed us to inject spin-polarised carriers from the La0.7Ca0.3MnO3 layer directly to the DyBa2Cu3O7- d micro-bridge (without any insulating buffer layer) making it possible to measure the critical current when polarised electrons alone are injected into the superconductor. Our results confirm the role of polarised carriers in breaking the Cooper pairs in the superconductor.Comment: 8 pages, 4 figure

Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. Currently, ∼8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR>1.3). In order to identify additional genes contributing to SLE susceptibility, we conducted a replication study in a UK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association analysis in the UK dataset and subsequent meta-analysis with the published data identified five SLE susceptibility genes reaching genome-wide levels of significance (Pcomb<5×10−8): NCF2 (Pcomb = 2.87×10−11), IKZF1 (Pcomb = 2.33×10−9), IRF8 (Pcomb = 1.24×10−8), IFIH1 (Pcomb = 1.63×10−8), and TYK2 (Pcomb = 3.88×10−8). Each of the five new loci identified here can be mapped into interferon signalling pathways, which are known to play a key role in the pathogenesis of SLE. These results increase the number of established susceptibility genes for lupus to ∼30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease

Peak effect and its evolution with defect structure in YBa2Cu3O7-d thin films at microwave frequencies

The vortex dynamics in YBa2Cu3O7-d thin films have been studied at microwave frequencies. A pronounced peak in the surface resistance, Rs, is observed in these films at frequencies of 4.88 and 9.55 GHz for magnetic fields varying from 0.2 to 0.8 T. The peak is associated with an order-disorder transformation of the flux line lattice as the temperature or field is increased. The occurrence of the peak in Rs is crucially dependent on the depinning frequency, wp and on the nature and concentration of growth defects present in these films. Introduction of artificial defects by swift heavy ion irradiation with 200 MeV Ag ion at a fluence of 4x1010 ions/cm2 enhances wp and suppresses the peak at 4.88 GHz but the peak at 9.55 GHz remains unaffected. A second peak at lower temperature has also been observed at 9.55 GHz. This is related to twin boundaries from angular dependence studies of Rs. Based on the temperature variation of Rs, vortex phase diagrams have been constructed at 9.55 GHz.Comment: 8 pages, 4 figures Submitted to Physical Review

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 = 2.3x10-21), A928V (rs35018800, OR = 0.53, P = 1.2x10-9), and I684S (rs12720356, OR = 0.86, P = 4.6x10-7). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6x10-18), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; Pomnibus = 0.005). Finally, in a phenomewide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 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

Decoding of Superimposed Traces Produced by Direct Sequencing of Heterozygous Indels

Direct Sanger sequencing of a diploid template containing a heterozygous insertion or deletion results in a difficult-to-interpret mixed trace formed by two allelic traces superimposed onto each other. Existing computational methods for deconvolution of such traces require knowledge of a reference sequence or the availability of both direct and reverse mixed sequences of the same template. We describe a simple yet accurate method, which uses dynamic programming optimization to predict superimposed allelic sequences solely from a string of letters representing peaks within an individual mixed trace. We used the method to decode 104 human traces (mean length 294 bp) containing heterozygous indels 5 to 30 bp with a mean of 99.1% bases per allelic sequence reconstructed correctly and unambiguously. Simulations with artificial sequences have demonstrated that the method yields accurate reconstructions when (1) the allelic sequences forming the mixed trace are sufficiently similar, (2) the analyzed fragment is significantly longer than the indel, and (3) multiple indels, if present, are well-spaced. Because these conditions occur in most encountered DNA sequences, the method is widely applicable. It is available as a free Web application Indelligent at http://ctap.inhs.uiuc.edu/dmitriev/indel.asp

Peak effect in a superconducting DyBa2Cu3O7-y film at microwave frequencies

We report the observation of a peak in the microwave (9.55 GHz) surface resistance in an epitaxial DyBa2Cu3O7-y superconducting film in magnetic fields (parallel to the c axis) ranging between 0.2 to 0.9 Tesla. Such a peak is absent in the measurements done in zero-field. The temperature and field dependence of the peak suggests that this peak could be associated with the peak effect phenomenon reflecting the order-disorder transformation in the flux-line lattice. A strong dependence of this peak effect at frequencies close to the depinning frequency of the flux line lattice is observed.Comment: 1 text, 4 figures (all postscript) to be published in Phys. Rev.

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.