Preface

Preface to first issue of Orbit

Electrostatic Potentials and Fields in the Vicinity of Engineered Nanostructures

We have developed a method of calculation of the electrostatic potentials and fields in the vicinity of geometrically complex engineered nanostructures comprised of varying materials in electrolytes of arbitrary pH and ionic strength. The method involves direct summation of charged Debye-Hueckel spheres comprising the nanostructural surfaces and, by including charge redistribution on the surface of conducting materials held at constant potential, is applicable to mixed boundary conditions. The method is validated by comparison to analytical solutions for an infinite plane (Gouy-Chapman), an infinite cylinder (Bessel functions) and an infinite plane which contains a hole and which is held at constant potential. Excellent agreement between the potentials obtained by our numerical method and the closed form solutions is found for these conditions. The method is applied to the calculation of the electric field enhancement in the vicinity of a nanomembrane whose pore wall is held at constant charge and whose membrane surfaces are held at constant potential. The electric field is found to be enhanced by the charge buildup in the rim of the hole of the nanomembrane, which redistribution results from the potential being held constant in the conducting region. Ion concentrations are also calculated; positive ion rejection is found to be enhanced by this charge buildup in the region of the rim when a constant positive potential is applied

Actes du 11e Colloque annuel de l'Association québécoise de pédagogie collégiale

Également disponible en version papierTitre de l'écran-titre (visionné le 7 août 2009)Bibliogr.: p. 1

Conceptualisation et surdité

Gratuit (1993)Également disponible en version papierTitre de l'écran-titre (visionné le 10 fév. 2010)Bibliogr.: p. 219-22

Erk1/2 MAP kinases are required for epidermal G2/M progression

Erk1/2 mitogen-activated protein kinases (MAPKs) are often hyperactivated in human cancers, where they affect multiple processes, including proliferation. However, the effects of Erk1/2 loss in normal epithelial tissue, the setting of most extracellular signal-regulated kinase (Erk)–associated neoplasms, are unknown. In epidermis, loss of Erk1 or Erk2 individually has no effect, whereas simultaneous Erk1/2 depletion inhibits cell division, demonstrating that these MAPKs are necessary for normal tissue self-renewal. Growth inhibition caused by Erk1/2 loss is rescued by reintroducing Erk2, but not by activating Erk effectors that promote G1 cell cycle progression. Unlike fibroblasts, in which Erk1/2 loss decreases cyclin D1 expression and induces G1/S arrest, Erk1/2 loss in epithelial cells reduces cyclin B1 and c-Fos expression and induces G2/M arrest while disrupting a gene regulatory network centered on cyclin B1–Cdc2. Thus, the cell cycle stages at which Erk1/2 activity is required vary by cell type, with Erk1/2 functioning in epithelial cells to enable progression through G2/M

Landscape Ecotoxicology of Coho Salmon Spawner Mortality in Urban Streams

In the Pacific Northwest of the United States, adult coho salmon (Oncorhynchus kisutch) returning from the ocean to spawn in urban basins of the Puget Sound region have been prematurely dying at high rates (up to 90% of the total runs) for more than a decade. The current weight of evidence indicates that coho deaths are caused by toxic chemical contaminants in land-based runoff to urban streams during the fall spawning season. Non-point source pollution in urban landscapes typically originates from discrete urban and residential land use activities. In the present study we conducted a series of spatial analyses to identify correlations between land use and land cover (roadways, impervious surfaces, forests, etc.) and the magnitude of coho mortality in six streams with different drainage basin characteristics. We found that spawner mortality was most closely and positively correlated with the relative proportion of local roads, impervious surfaces, and commercial property within a basin. These and other correlated variables were used to identify unmonitored basins in the greater Seattle metropolitan area where recurrent coho spawner die-offs may be likely. This predictive map indicates a substantial geographic area of vulnerability for the Puget Sound coho population segment, a species of concern under the U.S. Endangered Species Act. Our spatial risk representation has numerous applications for urban growth management, coho conservation, and basin restoration (e.g., avoiding the unintentional creation of ecological traps). Moreover, the approach and tools are transferable to areas supporting coho throughout western North America

French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known