Pattern Formation by Boundary Forcing in Convectively Unstable, Oscillatory Media With and Without Differential Transport

Motivated by recent experiments and models of biological segmentation, we analyze the exicitation of pattern-forming instabilities of convectively unstable reaction-diffusion-advection (RDA) systems, occuring by means of constant or periodic forcing at the upstream boundary. Such boundary-controlled pattern selection is a generalization of the flow-distributed oscillation (FDO) mechanism that can include Turing or differential flow instability (DIFI) modes. Our goal is to clarify the relationships among these mechanisms in the general case where there is differential flow as well as differential diffusion. We do so by analyzing the dispersion relation for linear perturbations and showing how its solutions are affected by differential transport. We find a close relationship between DIFI and FDO, while the Turing mechanism gives rise to a distinct set of unstable modes. Finally, we illustrate the relevance of the dispersion relations using nonlinear simulations and we discuss the experimental implications of our results.Comment: Revised version with added content (new section and figures added), changes to wording and organizatio

Versatility of global transcriptional regulators in alpha-Proteobacteria: from essential cell cycle control to ancillary functions

Recent data indicate that cell cycle transcription in many alpha-Proteobacteria is executed by at least three conserved functional modules in which pairs of antagonistic regulators act jointly, rather than in isolation, to control transcription in S-, G2- or G1-phase. Inactivation of module components often results in pleiotropic defects, ranging from cell death and impaired cell division to fairly benign deficiencies in motility. Expression of module components can follow systemic (cell cycle) or external (nutritional/cell density) cues and may be implemented by auto-regulation, ancillary regulators or other (unknown) mechanisms. Here, we highlight the recent progress in understanding the molecular events and the genetic relationships of the module components in environmental, pathogenic and/or symbiotic alpha-proteobacterial genera. Additionally, we take advantage of the recent genome-wide transcriptional analyses performed in the model alpha-Proteobacterium Caulobacter crescentus to illustrate the complexity of the interactions of the global regulators at selected cell cycle-regulated promoters and we detail the consequences of (mis-)expression when the regulators are absent. This review thus provides the first detailed mechanistic framework for understanding orthologous operational principles acting on cell cycle-regulated promoters in other alpha-Proteobacteri

What Is New in Clinical Microbiology—Microbial Identification by MALDI-TOF Mass Spectrometry A Paper from the 2011 William Beaumont Hospital Symposium on Molecular Pathology

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) offers the possibility of accurate, rapid, inexpensive identification of bacteria, fungi, and mycobacteria isolated in clinical microbiology laboratories. The procedures for preanalytic processing of organisms and analysis by MALDI-TOF MS are technically simple and reproducible, and commercial databases and interpretive algorithms are available for the identification of a wide spectrum of clinically significant organisms. Although only limited work has been reported on the use of this technique to identify molds, perform strain typing, or determine antibiotic susceptibility results, these are fruitful areas of promising research. As experience is gained with MALDI-TOF MS, it is expected that the databases will be expanded to resolve many of the current inadequate identifications (eg, no identification, genus-level identification) and algorithms for potential misidentification will be developed. The current lack of Food and Drug Administration approval of any MALDI-TOF MS system for organism identification limits widespread use in the United States

The 21-SPONGE HI Absorption Survey I: Techniques and Initial Results

We present methods and results from "21-cm Spectral Line Observations of Neutral Gas with the EVLA" (21-SPONGE), a large survey for Galactic neutral hydrogen (HI) absorption with the Karl G. Jansky Very Large Array (VLA). With the upgraded capabilities of the VLA, we reach median root-mean-square (RMS) noise in optical depth of $\sigma_{\tau}=9\times 10^{-4}$ per $0.42\rm\,km\,s^{-1}$ channel for the 31 sources presented here. Upon completion, 21-SPONGE will be the largest HI absorption survey with this high sensitivity. We discuss the observations and data reduction strategies, as well as line fitting techniques. We prove that the VLA bandpass is stable enough to detect broad, shallow lines associated with warm HI, and show that bandpass observations can be combined in time to reduce spectral noise. In combination with matching HI emission profiles from the Arecibo Observatory ($\sim3.5'$ angular resolution), we estimate excitation (or spin) temperatures ($\rm T_s$) and column densities for Gaussian components fitted to sightlines along which we detect HI absorption (30/31). We measure temperatures up to $\rm T_s\sim1500\rm\,K$ for individual lines, showing that we can probe the thermally unstable interstellar medium (ISM) directly. However, we detect fewer of these thermally unstable components than expected from previous observational studies. We probe a wide range in column density between $\sim10^{16}$ and $>10^{21}\rm\,cm^{-2}$ for individual HI clouds. In addition, we reproduce the trend between cold gas fraction and average $\rm T_s$ found by synthetic observations of a hydrodynamic ISM simulation by Kim et al. (2014). Finally, we investigate methods for estimating HI $\rm T_s$ and discuss their biases.Comment: Accepted for publication in ApJ; 24 pages, 14 figure

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Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership, U.S. Agency for International Development, U.K. Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin.Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization. Results: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group. Conclusions: The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting. (Funded by the Global Alliance for TB Drug Development and others; REMoxTB ClinicalTrials.gov number, NCT00864383.)Publisher PDFPeer reviewe