7 research outputs found

    Strong 3D correlations in vortex system of Bi2212:Pb

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    The experimental study of magnetic flux penetration under crossed magnetic fields in Bi2212:Pb single crystal performed by magnetooptic technique (MO) reveals remarkable field penetration pattern alteration (flux configuration change) and superconducting current anisotropy enhancement by the in-plane field. The anisotropy increases with the temperature rise up to Tm=54±2KT_m = 54 \pm 2 K. At T=TmT = T_m an abrupt change in the flux behavior is found; the correlation between the in-plane magnetic field and the out-of-plane magnetic flux penetration disappears. No correlation is observed for T>TmT > T_m. The transition temperature TmT_m does not depend on the magnetic field strength. The observed flux penetration anisotropy is considered as an evidence of a strong 3D - correlation between pancake vortices in different CuO planes at T<TmT < T_m. This enables understanding of a remarkable pinning observed in Bi2212:Pb at low temperatures.Comment: 8 pages, 9 figure

    Genome-wide association analysis identifies ancestry-specific genetic variation associated with acute response to metformin and glipizide in SUGAR-MGH

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    Aims/hypothesis Characterisation of genetic variation that influences the response to glucose-lowering medications is instrumental to precision medicine for treatment of type 2 diabetes. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH) examined the acute response to metformin and glipizide in order to identify new pharmacogenetic associations for the response to common glucose-lowering medications in individuals at risk of type 2 diabetes.Methods One thousand participants at risk for type 2 diabetes from diverse ancestries underwent sequential glipizide and metformin challenges. A genome-wide association study was performed using the Illumina Multi-Ethnic Genotyping Array. Imputation was performed with the TOPMed reference panel. Multiple linear regression using an additive model tested for association between genetic variants and primary endpoints of drug response. In a more focused analysis, we evaluated the influence of 804 unique type 2 diabetes- and glycaemic trait-associated variants on SUGAR-MGH outcomes and performed colocalisation analyses to identify shared genetic signals.Results Five genome-wide significant variants were associated with metformin or glipizide response. The strongest association was between an African ancestry-specific variant (minor allele frequency [MAF(Afr)]=0.0283) at rs149403252 and lower fasting glucose at Visit 2 following metformin (p=1.9x10(-9)); carriers were found to have a 0.94 mmol/l larger decrease in fasting glucose. rs111770298, another African ancestry-specific variant (MAF(Afr)=0.0536), was associated with a reduced response to metformin (p=2.4x10(-8)), where carriers had a 0.29 mmol/l increase in fasting glucose compared with non-carriers, who experienced a 0.15 mmol/l decrease. This finding was validated in the Diabetes Prevention Program, where rs111770298 was associated with a worse glycaemic response to metformin: heterozygous carriers had an increase in HbA(1c) of 0.08% and non-carriers had an HbA(1c) increase of 0.01% after 1 year of treatment (p=3.3x10(-3)). We also identified associations between type 2 diabetes-associated variants and glycaemic response, including the type 2 diabetes-protective C allele of rs703972 near ZMIZ1 and increased levels of active glucagon-like peptide 1 (GLP-1) (p=1.6x10(-5)), supporting the role of alterations in incretin levels in type 2 diabetes pathophysiology.Conclusions/interpretation We present a well-phenotyped, densely genotyped, multi-ancestry resource to study gene-drug interactions, uncover novel variation associated with response to common glucose-lowering medications and provide insight into mechanisms of action of type 2 diabetes-related variation.Clinical epidemiolog

    Genomics of tolerance to abiotic stress in the Triticeae

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    Genomics platforms offer unprecedented opportunities to identify, select and in some cases clone the genes and the quantitative trait loci (QTLs) that govern the tolerance of Triticeae to abiotic stresses and, consequently, grain yield. Transcriptome profiling and the other \u201comics\u201d platforms provide further information to unravel gene functions and validate the role of candidate genes. This review provides a synopsis of the main results on the studies that have investigated the genomics of Triticeae crops under conditions of abiotic constraints. With their rich biodiversity and high functional plasticity in response to environmental stresses, Triticeae crops provide an ideal ground for taking full advantage of the opportunities offered by genomics approaches. Ultimately, the practical impact of the knowledge and materials generated through genomics-based approaches will depend on their integration and exploitation within the extant breeding programs

    Genomics of Tolerance to Abiotic Stress in the Triticeae

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