The Dichotomy between Nodal and Antinodal Quasiparticles in Underdoped (La2−x_{2-x}Srx_x)CuO4_4 Superconductors

High resolution angle-resolved photoemission measurements on underdoped (La$_{2-x}$Sr$_x$)CuO$_4$ system show that, at energies below 70 meV, the quasiparticle peak is well defined around the ($\pi$/2,$\pi$/2) nodal region and disappears rather abruptly when the momentum is changed from the nodal point to the ($\pi$,0) antinodal point along the underlying ``Fermi surface''. It indicates that there is an extra low energy scattering mechanism acting upon the antinodal quasiparticles. We propose that this mechanism is the scattering of quasiparticles across the nearly parallel segments of the Fermi surface near the antinodes.Comment: to appear in Phys. Rev. Let

Pseudogap in a thin film of a conventional superconductor

A superconducting state is characterized by the gap in the electronic density of states which vanishes at the superconducting transition temperature Tc. It was discovered that in high temperature superconductors a noticeable depression in the density of states still remains even at temperatures above Tc; this feature being called pseudogap. Here we show that a pseudogap exists in a conventional superconductor: ultrathin titanium nitride films over a wide range of temperatures above Tc. Our study reveals that this pseudogap state is induced by superconducting fluctuations and favored by two-dimensionality and by the proximity to the transition to the insulating state. A general character of the observed phenomenon provides a powerful tool to discriminate between fluctuations as the origin of the pseudogap state, and other contributions in the layered high temperature superconductor compounds.Comment: 26 pages, 4 figure

Chromobacterium violaceum in Siblings, Brazil

Chromobacterium violaceum, a saprophyte bacterium found commonly in soil and water in tropical and subtropical climates, is a rare cause of severe, often fatal, human disease. We report 1 confirmed and 2 suspected cases of C. violaceum septicemia, with 2 fatalities, in siblings after recreational exposure in northeastern Brazil

Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells

Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in an concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog

False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women

Objective: Examine whether false-positive HIV enzyme immunoassay (EIA) test results occur more frequently among pregnant women than among women who are not pregnant and men (others). Design: To obtain a large number of pregnant women and others tested for HIV, we identified specimens tested at a national laboratory using Genetic Systems HIV-1/HIV-2 Plus O EIA from July 2007 to June 2008. Methods: Specimens with EIA repeatedly reactive and Western blot-negative or indeterminate results were considered EIA false-positive. We compared the false-positive rate among uninfected pregnant women and others, adjusting for HIV prevalence. Among all reactive EIAs, we evaluated the proportion of false-positives, positive predictive value (PPV), and Western blot bands among indeterminates, by pregnancy status. Results: HIV prevalence was 0.06 % among 921,438 pregnant women and 1.34 % among 1,103,961 others. The false-positive rate was lower for pregnant women than others (0.14 % vs. 0.21%, odds ratio 0.65 [95 % confidence interval 0.61, 0.70]). Pregnant women with reactive EIAs were more likely than others (p,0.01) to have Western blot-negative (52.9 % vs. 9.8%) and indeterminate results (17.0 % vs. 3.7%) and lower PPV (30 % vs. 87%). The p24 band was detected more often among pregnant women (p,0.01). Conclusions: False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others

Localization of preformed Cooper pairs in disordered superconductors

International audienceThe most profound effect of disorder on electronic systems is the localization of the electrons transforming an otherwise metallic system into an insulator. If the metal is also a superconductor then, at low temperatures, disorder can induce a pronounced transition from a superconducting into an insulating state. An outstanding question is whether the route to insulating behaviour proceeds through the direct localization of Cooper pairs or, alternatively, by a two-step process in which the Cooper pairing is first destroyed followed by the standard localization of single electrons. Here we address this question by studying the local superconducting gap of a highly disordered amorphous superconductor by means of scanning tunnelling spectroscopy. Our measurements reveal that, in the vicinity of the superconductor-insulator transition, the coherence peaks in the one-particle density of states disappear whereas the superconducting gap remains intact, indicating the presence of localized Cooper pairs. Our results provide the first direct evidence that the superconductor-insulator transition in some homogeneously disordered materials is driven by Cooper-pair localization

A physicochemical descriptor-based scoring scheme for effective and rapid filtering of kinase-like chemical space

<p>Abstract</p> <p>Background</p> <p>The current chemical space of known small molecules is estimated to exceed 10⁶⁰structures. Though the largest physical compound repositories contain only a few tens of millions of unique compounds, virtual screening of databases of this size is still difficult. In recent years, the application of physicochemical descriptor-based profiling, such as Lipinski's rule-of-five for drug-likeness and Oprea's criteria of lead-likeness, as early stage filters in drug discovery has gained widespread acceptance. In the current study, we outline a kinase-likeness scoring function based on known kinase inhibitors.</p> <p>Results</p> <p>The method employs a collection of 22,615 known kinase inhibitors from the ChEMBL database. A kinase-likeness score is computed using statistical analysis of nine key physicochemical descriptors for these inhibitors. Based on this score, the kinase-likeness of four publicly and commercially available databases, i.e., National Cancer Institute database (NCI), the Natural Products database (NPD), the National Institute of Health's Molecular Libraries Small Molecule Repository (MLSMR), and the World Drug Index (WDI) database, is analyzed. Three of these databases, i.e., NCI, NPD, and MLSMR are frequently used in the virtual screening of kinase inhibitors, while the fourth WDI database is for comparison since it covers a wide range of known chemical space. Based on the kinase-likeness score, a kinase-focused library is also developed and tested against three different kinase targets selected from three different branches of the human kinome tree.</p> <p>Conclusions</p> <p>Our proposed methodology is one of the first that explores how the narrow chemical space of kinase inhibitors and its relevant physicochemical information can be utilized to build kinase-focused libraries and prioritize pre-existing compound databases for screening. We have shown that focused libraries generated by filtering compounds using the kinase-likeness score have, on average, better docking scores than an equivalent number of randomly selected compounds. Beyond library design, our findings also impact the broader efforts to identify kinase inhibitors by screening pre-existing compound libraries. Currently, the NCI library is the most commonly used database for screening kinase inhibitors. Our research suggests that other libraries, such as MLSMR, are more kinase-like and should be given priority in kinase screenings.</p

ProbABEL package for genome-wide association analysis of imputed data

Background: Over the last few years, genome-wide association (GWA) studies became a tool of choice for the identification of loci associated with complex traits. Currently, imputed single nucleotide polymorphisms (SNP) data are frequently used in GWA analyzes. Correct analysis of imputed data calls for the implementation of specific methods which take genotype imputation uncertainty into account.Results: We developed the ProbABEL software package for the analysis of genome-wide imputed SNP data and quantitative, binary, and time-till-event outcomes under linear, logistic, and Cox proportional hazards models, respectively. For quantitative traits, the package also implements a fast two-step mixed model-based score test for association in samples with differential relationships, facilitating analysis in family-based studies, studies performed in human genetically isolated populations and outbred animal populations.Conclusions: ProbABEL package provides fast efficient way to analyze imputed data in genome-wide context and will facilitate future identification of complex trait loci