Lucky 13-microtubule depolymerisation by kinesin-13 motors

The kinesin-13 class of motors catalyses microtubule depolymerisation by bending tubulins at microtubule ends. Depolymerisation activity is intrinsic to the kinesin-13 motor core but the activity of the core alone is very low compared with that of constructs that also contain a conserved neck sequence. The full-length dimeric motor is an efficient depolymeriser and also diffuses along the microtubule lattice, which helps it to find microtubule ends. Current evidence supports the idea of a generic mechanism for kinesin-13-catalysed depolymerisation. However, the activity of kinesin-13 motors is precisely localised and regulated in vivo to enable a wide range of cellular roles. The proteins are involved in global control of microtubule dynamics. They also localise to mitotic and meiotic spindles, where they contribute to formation and maintenance of spindle bipolarity, chromosomal congression, attachment correction and chromatid separation. In interphase cells, intricate and subtle mechanisms appear to allow kinesin-13 motors to act on specific populations of microtubules. Such carefully controlled localisation and regulation makes these kinesins efficient, multi-tasking molecular motors

Extreme Ultra-Violet Spectroscopy of the Lower Solar Atmosphere During Solar Flares

The extreme ultraviolet portion of the solar spectrum contains a wealth of diagnostic tools for probing the lower solar atmosphere in response to an injection of energy, particularly during the impulsive phase of solar flares. These include temperature and density sensitive line ratios, Doppler shifted emission lines and nonthermal broadening, abundance measurements, differential emission measure profiles, and continuum temperatures and energetics, among others. In this paper I shall review some of the advances made in recent years using these techniques, focusing primarily on studies that have utilized data from Hinode/EIS and SDO/EVE, while also providing some historical background and a summary of future spectroscopic instrumentation.Comment: 34 pages, 8 figures. Submitted to Solar Physics as part of the Topical Issue on Solar and Stellar Flare

New Insights into White-Light Flare Emission from Radiative-Hydrodynamic Modeling of a Chromospheric Condensation

(abridged) The heating mechanism at high densities during M dwarf flares is poorly understood. Spectra of M dwarf flares in the optical and near-ultraviolet wavelength regimes have revealed three continuum components during the impulsive phase: 1) an energetically dominant blackbody component with a color temperature of T $\sim$ 10,000 K in the blue-optical, 2) a smaller amount of Balmer continuum emission in the near-ultraviolet at lambda $<$ 3646 Angstroms and 3) an apparent pseudo-continuum of blended high-order Balmer lines. These properties are not reproduced by models that employ a typical "solar-type" flare heating level in nonthermal electrons, and therefore our understanding of these spectra is limited to a phenomenological interpretation. We present a new 1D radiative-hydrodynamic model of an M dwarf flare from precipitating nonthermal electrons with a large energy flux of $10^{13}$ erg cm$^{-2}$ s$^{-1}$. The simulation produces bright continuum emission from a dense, hot chromospheric condensation. For the first time, the observed color temperature and Balmer jump ratio are produced self-consistently in a radiative-hydrodynamic flare model. We find that a T $\sim$ 10,000 K blackbody-like continuum component and a small Balmer jump ratio result from optically thick Balmer and Paschen recombination radiation, and thus the properties of the flux spectrum are caused by blue light escaping over a larger physical depth range compared to red and near-ultraviolet light. To model the near-ultraviolet pseudo-continuum previously attributed to overlapping Balmer lines, we include the extra Balmer continuum opacity from Landau-Zener transitions that result from merged, high order energy levels of hydrogen in a dense, partially ionized atmosphere. This reveals a new diagnostic of ambient charge density in the densest regions of the atmosphere that are heated during dMe and solar flares.Comment: 50 pages, 2 tables, 13 figures. Accepted for publication in the Solar Physics Topical Issue, "Solar and Stellar Flares". Version 2 (June 22, 2015): updated to include comments by Guest Editor. The final publication is available at Springer via http://dx.doi.org/10.1007/s11207-015-0708-

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation