Quasiparticle excitation in and around the vortex core of underdoped YBa_2Cu_4O_8 studied by site-selective NMR

We report a site-selective ^{17}O spin-lattice relaxation rate T_1^{-1} in the vortex state of underdoped YBa_2Cu_4O_8. We found that T_1^{-1} at the planar sites exhibits an unusual nonmonotonic NMR frequency dependence. In the region well outside the vortex core, T_1^{-1} cannot be simply explained by the density of states of the Doppler-shifted quasiparticles in the d-wave superconductor. Based on T_1^{-1} in the vortex core region, we establish strong evidence that the local density of states within the vortex core is strongly reduced.Comment: 5 pages, 3 figure

Path Integral Description of a Semiclassical Su-Schrieffer-Heeger Model

The electron motion along a chain is described by a continuum version of the Su-Schrieffer-Heeger Hamiltonian in which phonon fields and electronic coordinates are mapped onto the time scale. The path integral formalism allows us to derive the non local source action for the particle interacting with the oscillators bath. The method can be applied for any value of the {\it e-ph} coupling. The path integral dependence on the model parameters has been analysed by computing the partition function and some thermodynamical properties from $T= 1K$ up to room temperature. A peculiar upturn in the low temperature {\it heat capacity over temperature} ratio (pointing to a glassy like behavior) has been ascribed to the time dependent electronic hopping along the chain

Determination of polarized parton distribution functions and their uncertainties

We investigate the polarized parton distribution functions (PDFs) and their uncertainties by using the world data on the spin asymmetry A_1. The uncertainties of the polarized PDFs are estimated by the Hessian method. The up and down valence-quark distributions are determined well. However, the antiquark distributions have large uncertainties at this stage, and it is particularly difficult to fix the gluon distribution. The \chi^2 analysis produces a positively polarized gluon distribution, but even \Delta g(x)=0 could be allowed according to our uncertainty estimation. In comparison with the previous AAC (Asymmetry Analysis Collaboration) parameterization in 2000, accurate SLAC-E155 proton data are added to the analysis. We find that the E155 data improve the determination of the polarized PDFs, especially the polarized antiquark distributions. In addition, the gluon-distribution uncertainties are reduced due to the correlation with the antiquark distributions. We also show the global analysis results with the condition \Delta g(x)=0 at the initial scale, Q^2=1 GeV^2, for clarifying the error correlation effects with the gluon distribution.Comment: 9 pages, 15 eps figures, REVTeX, FORTRAN package is available at the web site http://www-hs.phys.saga-u.ac.jp/aac.html. Replaced 3 eps figures in Fig.

Association between glycated haemoglobin levels and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the TECOS randomized clinical trial

Aims: Whether glycaemic control is associated with cardiovascular outcomes in patients with type 2 diabetes (T2D) is unclear. Consequently, we assessed the relationship between glycated haemoglobin (HbA1c) and cardiovascular outcomes in a placebo-controlled randomized trial which demonstrated no cardiovascular effect of sitagliptin in patients with T2D and atherosclerotic vascular disease. Methods and results: Secondary analysis of 14 656 TECOS participants with time to event analyses using multivariable Cox proportional hazard models. During a median 3.0 (interquartile range 2.3–3.8) year follow-up, 456 (3.1% of 14 656) patients had first hospitalization for heart failure (HF), 1084 (11.5%) died, 1406 (9.6%) died or were hospitalized for HF, and 1689 (11.5%) had a non-HF cardiovascular event (cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, or hospitalization for unstable angina). Associations between baseline or time-varying HbA1c and cardiovascular outcomes were U-shaped, with the lowest risk when HbA1c was around 7%. Each one-unit increase in the time-varying HbA1c above 7% was associated with an adjusted hazard ratio (HR) of 1.21 [95% confidence interval (CI) 1.11–1.33] for first HF hospitalization, 1.11 (1.03–1.21) for all-cause death, 1.18 (1.09–1.26) for death or HF hospitalization, and 1.10 (1.02–1.17) for non-HF cardiovascular events. Each one-unit decrease in the time-varying HbA1c below 7% was associated with an adjusted HR of 1.35 (95% CI 1.12–1.64) for first HF hospitalization, 1.37 (1.16–1.61) for death, 1.42 (1.23–1.64) for death or HF hospitalization, and 1.22 (1.06–1.41) for non-HF cardiovascular events. Conclusion: Glycated haemogobin exhibits a U-shaped association with cardiovascular outcomes in patients with T2D and atherosclerotic vascular disease, with nadir around 7%. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT00790205

Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics

Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases

Decadal Variabilities in Tropospheric Nitrogen Oxides Over United States, Europe, and China

Global trends in tropospheric nitrogen dioxide (NO2) have changed dramatically in the past decade. Here, we investigate tropospheric NO2 variabilities over United States, Europe, and E. China in 2005–2018 to explore the mechanisms governing the variation of this critical pollutant. We found large uncertainties in the trends of anthropogenic nitrogen oxides (NOx) emissions, for example, the reductions of NOx emissions, derived with different approaches and data sets, are in the range of 35%–50% over the United States and 15%–45% over Europe in 2005–2018. By contrast, the analysis in this work indicates declines of anthropogenic NOx emissions by about 40% and 25% over the United States and Europe, respectively, in 2005–2018, and about 20% over E. China in 2012–2018. However, the shift of major NOx sources from power generation to industrial and transportation sectors has led to noticeable diminishing effects in emission controls. Furthermore, satellite measurements exhibit the influence of NO2 background levels over the United States and Europe, which offset the impacts of anthropogenic emission declines, resulting in flatter trends of tropospheric NO2 over the United States and Europe. Our analysis further reveals underestimation of background NO2 by chemical transport models, which can lead to inaccurate interpretations of satellite measurements. We use surface in-situ NO2 observations to diagnose the satellite-observed NO2 trends and find top-down NOx emissions over urban grids represent the changes in anthropogenic NOx emissions better. This work highlights the importance of comprehensive applications of different analysis approaches to better characterizing atmospheric composition evolution

Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine

OBJECTIVE Phenotypic heterogeneity among patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) is ill defined. We used cluster analysis machine-learning algorithms to identify phenotypes among trial participants with T2DM and ASCVD. RESEARCH DESIGN AND METHODS We used data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study (n = 14,671), a cardiovascular outcome safety trial comparing sitagliptin with placebo in patients with T2DM and ASCVD (median follow-up 3.0 years). Cluster analysis using 40 baseline variables was conducted, with associations between clusters and the primary composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina) assessed by Cox proportional hazards models. We replicated the results using the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial. RESULTS Four distinct phenotypes were identified: Cluster I included Caucasian men with a high prevalence of coronary artery disease; cluster II included Asian patients with a low BMI; cluster III included women with noncoronary ASCVD disease; and cluster IV included patients with heart failure and kidney dysfunction. The primary outcome occurred, respectively, in 11.6%, 8.6%, 10.3%, and 16.8% of patients in clusters I to IV. The crude difference in cardiovascular risk for the highest versus lowest risk cluster (cluster IV vs. II) was statistically significant (hazard ratio 2.74 [95% CI 2.29–3.29]). Similar phenotypes and outcomes were identified in EXSCEL. CONCLUSIONS In patients with T2DM and ASCVD, cluster analysis identified four clinically distinct groups. Further cardiovascular phenotyping is warranted to inform patient care and optimize clinical trial designs

Applications of electrified dust and dust devil electrodynamics to Martian atmospheric electricity

Atmospheric transport and suspension of dust frequently brings electrification, which may be substantial. Electric fields of 10 kVm-1 to 100 kVm-1 have been observed at the surface beneath suspended dust in the terrestrial atmosphere, and some electrification has been observed to persist in dust at levels to 5 km, as well as in volcanic plumes. The interaction between individual particles which causes the electrification is incompletely understood, and multiple processes are thought to be acting. A variation in particle charge with particle size, and the effect of gravitational separation explains to, some extent, the charge structures observed in terrestrial dust storms. More extensive flow-based modelling demonstrates that bulk electric fields in excess of 10 kV m-1 can be obtained rapidly (in less than 10 s) from rotating dust systems (dust devils) and that terrestrial breakdown fields can be obtained. Modelled profiles of electrical conductivity in the Martian atmosphere suggest the possibility of dust electrification, and dust devils have been suggested as a mechanism of charge separation able to maintain current flow between one region of the atmosphere and another, through a global circuit. Fundamental new understanding of Martian atmospheric electricity will result from the ExoMars mission, which carries the DREAMS (Dust characterization, Risk Assessment, and Environment Analyser on the Martian Surface)-MicroARES (Atmospheric Radiation and Electricity Sensor) instrumentation to Mars in 2016 for the first in situ measurements

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation