Large disk-like galaxies at high redshift

Using deep near-infrared imaging of the Hubble Deep Field South with ISAAC on the Very Large Telescope we find 6 large disk-like galaxies at redshifts z = 1.4-3.0. The galaxies, selected in K_s (2.2 micron), are regular and surprisingly large in the near-infrared (rest-frame optical), with face-on effective radii r_e = 0.65"-0.9" or 5.0-7.5 h_70^-1 kpc in a Lambda-CDM cosmology, comparable to the Milky Way. The surface brightness profiles are consistent with an exponential law over 2-3 effective radii. The WFPC2 morphologies in Hubble Space Telescope imaging (rest-frame UV) are irregular and show complex aggregates of star-forming regions ~2" (~15 h_70^-1 kpc) across, symmetrically distributed around the K_s-band centers. The spectral energy distributions show clear breaks in the rest-frame optical. The breaks are strongest in the central regions of the galaxies, and can be identified as the age-sensitive Balmer/4000 Angstrom break. The most straightforward interpretation is that these galaxies are large disk galaxies; deep NIR data are indispensable for this classification. The candidate disks constitute 50% of galaxies with L_V > 6 x 10^10 h_70^-2 L_sun at z = 1.4-3.0. This discovery was not expected on the basis of previously studied samples. In particular, the Hubble Deep Field North is deficient in large galaxies with the morphologies and profiles we report here.Comment: LaTeX, 5 pages, 2 figures, 1 table. Accepted for publication in the Astrophysical Journal Letter

A Predictive Model of the Oxygen and Heme Regulatory Network in Yeast

Deciphering gene regulatory mechanisms through the analysis of high-throughput expression data is a challenging computational problem. Previous computational studies have used large expression datasets in order to resolve fine patterns of coexpression, producing clusters or modules of potentially coregulated genes. These methods typically examine promoter sequence information, such as DNA motifs or transcription factor occupancy data, in a separate step after clustering. We needed an alternative and more integrative approach to study the oxygen regulatory network in Saccharomyces cerevisiae using a small dataset of perturbation experiments. Mechanisms of oxygen sensing and regulation underlie many physiological and pathological processes, and only a handful of oxygen regulators have been identified in previous studies. We used a new machine learning algorithm called MEDUSA to uncover detailed information about the oxygen regulatory network using genome-wide expression changes in response to perturbations in the levels of oxygen, heme, Hap1, and Co2+. MEDUSA integrates mRNA expression, promoter sequence, and ChIP-chip occupancy data to learn a model that accurately predicts the differential expression of target genes in held-out data. We used a novel margin-based score to extract significant condition-specific regulators and assemble a global map of the oxygen sensing and regulatory network. This network includes both known oxygen and heme regulators, such as Hap1, Mga2, Hap4, and Upc2, as well as many new candidate regulators. MEDUSA also identified many DNA motifs that are consistent with previous experimentally identified transcription factor binding sites. Because MEDUSA's regulatory program associates regulators to target genes through their promoter sequences, we directly tested the predicted regulators for OLE1, a gene specifically induced under hypoxia, by experimental analysis of the activity of its promoter. In each case, deletion of the candidate regulator resulted in the predicted effect on promoter activity, confirming that several novel regulators identified by MEDUSA are indeed involved in oxygen regulation. MEDUSA can reveal important information from a small dataset and generate testable hypotheses for further experimental analysis. Supplemental data are included

Thickness-dependent optimization of Er³⁺light emission from silicon-rich silicon oxide thin films

Abstract This study investigates the influence of the film thickness on the silicon-excess-mediated sensitization of Erbium ions in Si-rich silica. The Er3+ photoluminescence at 1.5 &#956;m, normalized to the film thickness, was found five times larger for films 1 &#956;m-thick than that from 50-nm-thick films intended for electrically driven devices. The origin of this difference is shared by changes in the local density of optical states and depth-dependent interferences, and by limited formation of Si-based sensitizers in "thin" films, probably because of the prevailing high stress. More Si excess has significantly increased the emission from "thin" films, up to ten times. This paves the way to the realization of highly efficient electrically excited devices.</p

Uncovering the Missing Link between Molecular Electrochemistry and Electrocatalysis: Mechanism of the Reduction of Benzyl Chloride at Silver Cathodes

Herein, the traditional views that contrast the important areas of electrocatalysis and molecular electrochemistry are challenged. By extending Laviron\u2019s seminal concept, we show that these two domains only represent idealized limits of a much broader continuum. More importantly, we show that electrochemical systems that apparently behave experimentally as if under diffusion control (i.e. systems that obey the founding molecular electrochemistry paradigm) may be controlled by electrocatalytic steps, that is, in which the activation of electroactive substrates exclusively occurs through adsorbed intermediates. This analysis is supported through quantitative experimental and theoretical investigations on the reduction of benzyl chloride at silver electrodes. At silver cathodes, the reduction wave of benzyl chloride as monitored at the usual scan rates is dramatically shifted to more positive potentials by about 0.5 V versus that at inert (e.g. glassy carbon) electrodes. This approach, which is based on the use of fast-scan cyclic voltammetry and simulations (KISSA-1D), combined with our previous results from surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT) analysis, allow us to fully unravel the mechanistic origin of this dramatic effect and quantitatively validate this mechanism, which has eluded many research groups until now. In practice, this example provides a missing link between the traditional areas of electrocatalysis and molecular electrochemistry. Furthermore, it bridges the chemical areas of organometallic/inorganic catalysis and electrochemical activation by showing that the inner-sphere concept, as developed by Taube and Myers for inorganic reactions, applies perfectly to electrochemical reactions of molecular substrate

Effect of an antiretroviral regimen containing ritonavir boosted lopinavir on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients

This study aimed to quantify the inhibition of cytochrome P450 (CYP3A), CYP2D6, and P-glycoprotein in human immunodeficiency virus (HIV)-infected patients receiving an antiretroviral therapy (ART) containing ritonavir boosted lopinavir, and to identify factors influencing ritonavir and lopinavir pharmacokinetics. We measured activities of CYP3A, CYP2D6, and P-glycoprotein in 28 patients before and during ART using a cocktail phenotyping approach. Activities, demographics, and genetic polymorphisms in CYP3A, CYP2D6, and P-glycoprotein were tested as covariates. Oral midazolam clearance (overall CYP3A activity) decreased to 0.19-fold (90% confidence interval (CI), 0.15-0.23), hepatic midazolam clearance and intestinal midazolam availability changed to 0.24-fold (0.20-0.29) and 1.12-fold (1.00-1.26), respectively. In CYP2D6 extensive metabolizers, the plasma ratio AUC(dextromethorphan)/AUC(dextrorphan) increased to 2.92-fold (2.31-3.69). Digoxin area under the curve (AUC)(0-12) (P-glycoprotein activity) increased to 1.81-fold (1.56-2.09). Covariates had no major influence on lopinavir and ritonavir pharmacokinetics. In conclusion, CYP3A, CYP2D6, and P-glycoprotein are profoundly inhibited in patients receiving ritonavir boosted lopinavir. The covariates investigated are not useful for a priori dose selection