Symmetry and correlation effects on band structure explain the anomalous transport properties of (111) LaAlO3_3/SrTiO3_3

The interface between the two insulating oxides SrTiO$_3$ and LaAlO$_3$ gives rise to a two-dimensional electron system with intriguing transport phenomena, including superconductivity, which are controllable by a gate. Previous measurements on the (001) interface have shown that the superconducting critical temperature, the Hall density, and the frequency of quantum oscillations, vary nonmonotonically and in a correlated fashion with the gate voltage. In this paper we experimentally demonstrate that the (111) interface features a qualitatively distinct behavior, in which the frequency of Shubnikov-de Haas oscillations changes monotonically, while the variation of other properties is nonmonotonic albeit uncorrelated. We develop a theoretical model, incorporating the different symmetries of these interfaces as well as electronic-correlation-induced band competition. We show that the latter dominates at (001), leading to similar nonmonotonicity in all observables, while the former is more important at (111), giving rise to highly curved Fermi contours, and accounting for all its anomalous transport measurements.Comment: 6+7 pages, 4+6 figures, Published Versio

Genome-Wide Profiling of Histone H3 Lysine 4 and Lysine 27 Trimethylation Reveals an Epigenetic Signature in Prostate Carcinogenesis

BACKGROUND: Increasing evidence implicates the critical roles of epigenetic regulation in cancer. Very recent reports indicate that global gene silencing in cancer is associated with specific epigenetic modifications. However, the relationship between epigenetic switches and more dynamic patterns of gene activation and repression has remained largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide profiling of the trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) was performed using chromatin immunoprecipitation coupled with whole genome promoter microarray (ChIP-chip) techniques. Comparison of the ChIP-chip data and microarray gene expression data revealed that loss and/or gain of H3K4me3 and/or H3K27me3 were strongly associated with differential gene expression, including microRNA expression, between prostate cancer and primary cells. The most common switches were gain or loss of H3K27me3 coupled with low effect on gene expression. The least prevalent switches were between H3K4me3 and H3K27me3 coupled with much higher fractions of activated and silenced genes. Promoter patterns of H3K4me3 and H3K27me3 corresponded strongly with coordinated expression changes of regulatory gene modules, such as HOX and microRNA genes, and structural gene modules, such as desmosome and gap junction genes. A number of epigenetically switched oncogenes and tumor suppressor genes were found overexpressed and underexpressed accordingly in prostate cancer cells. CONCLUSIONS/SIGNIFICANCE: This work offers a dynamic picture of epigenetic switches in carcinogenesis and contributes to an overall understanding of coordinated regulation of gene expression in cancer. Our data indicate an H3K4me3/H3K27me3 epigenetic signature of prostate carcinogenesis

Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism

BACKGROUND: The revised Geneva score is a fully standardized clinical decision rule (CDR) in the diagnostic workup of patients with suspected pulmonary embolism (PE). The variables of the decision rule have different weights, which could lead to miscalculations in an acute setting. We have validated a simplified version of the revised Geneva score. METHODS: Data from 1049 patients from 2 large prospective diagnostic trials that included patients with suspected PE were used and combined to validate the simplified revised Geneva score. We constructed the simplified CDR by attributing 1 point to each item of the original CDR and compared the diagnostic accuracy of the 2 versions by a receiver operating characteristic curve analysis. We also assessed the clinical utility of the simplified CDR by evaluating the safety of ruling out PE on the basis of the combination of either a low-intermediate clinical probability (using a 3-level scheme) or a "PE unlikely" assessment (using a dichotomized rule) with a normal result on a highly sensitive D-dimer test. RESULTS: The complete study population had an overall prevalence of venous thromboembolism of 23%. The diagnostic accuracy between the 2 CDRs did not differ (area under the curve for the revised Geneva score was 0.75 [95% confidence interval, 0.71-0.78] vs 0.74 [0.70-0.77] for the simplified revised Geneva score). During 3 months of follow-up, no patient with a combination of either a low (0%; 95% confidence interval, 0.0%-1.7%) or intermediate (0%; 0.0%-2.8%) clinical probability, or a "PE unlikely" assessment (0%; 0.0%-1.2%) with the simplified score and a normal result of a D-dimer test was diagnosed as having venous thromboembolism. CONCLUSION: This study suggests that simplification of the revised Geneva score does not lead to a decrease in diagnostic accuracy and clinical utility, which should be confirmed in a prospective study

Optimized small‐molecule pull‐downs define MLBP

Abscisic acid (ABA) receptors belong to the START domain superfamily, which encompasses ligand-binding proteins present in all kingdoms of life. START domain proteins contain a central binding pocket that, depending on the protein, can couple ligand binding to catalytic, transport or signaling functions. In Arabidopsis, the best characterized START domain proteins are the 14 PYR/PYL/RCAR ABA receptors, while the other members of the superfamily do not have assigned ligands. To address this, we used affinity purification of biotinylated proteins expressed transiently in Nicotiana benthamiana coupled to untargeted LC-MS to identify candidate binding ligands. We optimized this method using ABA–PYL interactions and show that ABA co-purifies with wild-type PYL5 but not a binding site mutant. The Kd of PYL5 for ABA is 1.1 μm, which suggests that the method has sufficient sensitivity for many ligand–protein interactions. Using this method, we surveyed a set of 37 START domain-related proteins, which resulted in the identification of ligands that co-purified with MLBP1 (At4G01883) or MLP165 (At1G35260). Metabolite identification and the use of authentic standards revealed that MLBP1 binds to monolinolenin, which we confirmed using recombinant MLBP1. Monolinolenin also co-purified with MLBP1 purified from transgenic Arabidopsis, demonstrating that the interaction occurs in a native context. Thus, deployment of this relatively simple method allowed us to define a protein–metabolite interaction and better understand protein–ligand interactions in plants