Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

PMCID: PMC3473050This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Physical activity interventions and therapeutic exercise in adults with rare neurological disorders: development of a core outcome measure set

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Mean flow and spiral defect chaos in Rayleigh-Benard convection

We describe a numerical procedure to construct a modified velocity field that does not have any mean flow. Using this procedure, we present two results. Firstly, we show that, in the absence of mean flow, spiral defect chaos collapses to a stationary pattern comprising textures of stripes with angular bends. The quenched patterns are characterized by mean wavenumbers that approach those uniquely selected by focus-type singularities, which, in the absence of mean flow, lie at the zig-zag instability boundary. The quenched patterns also have larger correlation lengths and are comprised of rolls with less curvature. Secondly, we describe how mean flow can contribute to the commonly observed phenomenon of rolls terminating perpendicularly into lateral walls. We show that, in the absence of mean flow, rolls begin to terminate into lateral walls at an oblique angle. This obliqueness increases with Rayleigh number.Comment: 14 pages, 19 figure

Bifurcation and chaos in zero Prandtl number convection

We present the detailed bifurcation structure and associated flow patterns near the onset of zero Prandtl number Rayleigh B\'enard convection. We employ both direct numerical simulation and a low-dimensional model ensuring qualitative agreement between the two. Various flow patterns originate from a stationary square observed at a higher Rayleigh number through a series of bifurcations starting from a pitchfork followed by a Hopf and finally a homoclinic bifurcation as the Rayleigh number is reduced to the critical value. Global chaos, intermittency, and crises are observed near the onset.Comment: 4 pages, 4 figure

Efficient Algorithm on a Non-staggered Mesh for Simulating Rayleigh-Benard Convection in a Box

An efficient semi-implicit second-order-accurate finite-difference method is described for studying incompressible Rayleigh-Benard convection in a box, with sidewalls that are periodic, thermally insulated, or thermally conducting. Operator-splitting and a projection method reduce the algorithm at each time step to the solution of four Helmholtz equations and one Poisson equation, and these are are solved by fast direct methods. The method is numerically stable even though all field values are placed on a single non-staggered mesh commensurate with the boundaries. The efficiency and accuracy of the method are characterized for several representative convection problems.Comment: REVTeX, 30 pages, 5 figure

Characterisation of the enzyme transport path between shipworms and their bacterial symbionts.

BACKGROUND: Shipworms are marine xylophagus bivalve molluscs, which can live on a diet solely of wood due to their ability to produce plant cell wall-degrading enzymes. Bacterial carbohydrate-active enzymes (CAZymes), synthesised by endosymbionts living in specialised shipworm cells called bacteriocytes and located in the animal's gills, play an important role in wood digestion in shipworms. However, the main site of lignocellulose digestion within these wood-boring molluscs, which contains both endogenous lignocellulolytic enzymes and prokaryotic enzymes, is the caecum, and the mechanism by which bacterial enzymes reach the distant caecum lumen has remained so far mysterious. Here, we provide a characterisation of the path through which bacterial CAZymes produced in the gills of the shipworm Lyrodus pedicellatus reach the distant caecum to contribute to the digestion of wood. RESULTS: Through a combination of transcriptomics, proteomics, X-ray microtomography, electron microscopy studies and in vitro biochemical characterisation, we show that wood-digesting enzymes produced by symbiotic bacteria are localised not only in the gills, but also in the lumen of the food groove, a stream of mucus secreted by gill cells that carries food particles trapped by filter feeding to the mouth. Bacterial CAZymes are also present in the crystalline style and in the caecum of their shipworm host, suggesting a unique pathway by which enzymes involved in a symbiotic interaction are transported to their site of action. Finally, we characterise in vitro four new bacterial glycosyl hydrolases and a lytic polysaccharide monooxygenase identified in our transcriptomic and proteomic analyses as some of the major bacterial enzymes involved in this unusual biological system. CONCLUSION: Based on our data, we propose that bacteria and their enzymes are transported from the gills along the food groove to the shipworm's mouth and digestive tract, where they aid in wood digestion

Removal of glucuronic acid from xylan is a strategy to improve the conversion of plant biomass to sugars for bioenergy

BACKGROUND: Plant lignocellulosic biomass can be a source of fermentable sugars for the production of second generation biofuels and biochemicals. The recalcitrance of this plant material is one of the major obstacles in its conversion into sugars. Biomass is primarily composed of secondary cell walls, which is made of cellulose, hemicelluloses and lignin. Xylan, a hemicellulose, binds to the cellulose microfibril and is hypothesised to form an interface between lignin and cellulose. Both softwood and hardwood xylan carry glucuronic acid side branches. As xylan branching may be important for biomass recalcitrance and softwood is an abundant, non-food competing, source of biomass it is important to investigate how conifer xylan is synthesised. RESULTS: Here, we show using Arabidopsis gux mutant biomass that removal of glucuronosyl substitutions of xylan can allow 30% more glucose and over 700% more xylose to be released during saccharification. Ethanol yields obtained through enzymatic saccharification and fermentation of gux biomass were double those obtained for non-mutant material. Our analysis of additional xylan branching mutants demonstrates that absence of GlcA is unique in conferring the reduced recalcitrance phenotype. As in hardwoods, conifer xylan is branched with GlcA. We use transcriptomic analysis to identify conifer enzymes that might be responsible for addition of GlcA branches onto xylan in industrially important softwood. Using a combination of in vitro and in vivo activity assays, we demonstrate that a white spruce (Picea glauca) gene, PgGUX, encodes an active glucuronosyl transferase. Glucuronic acid introduced by PgGUX reduces the sugar release of Arabidopsis gux mutant biomass to wild-type levels indicating that it can fulfil the same biological function as native glucuronosylation. CONCLUSION: Removal of glucuronic acid from xylan results in the largest increase in release of fermentable sugars from Arabidopsis plants that grow to the wild-type size. Additionally, plant material used in this work did not undergo any chemical pretreatment, and thus increased monosaccharide release from gux biomass can be achieved without the use of environmentally hazardous chemical pretreatment procedures. Therefore, the identification of a gymnosperm enzyme, likely to be responsible for softwood xylan glucuronosylation, provides a mutagenesis target for genetically improved forestry trees.This work was supported by the Leverhulme Trust Centre for Natural Material Innovation and the OpenPlant Synthetic Biology Research Centre. J.J.L. was in receipt of a studentship from the Biotechnology and Biological Sciences Research Council (BBSRC) of the UK as part of the Cambridge BBSRC-DTP Programme (Reference BB/J014540/1). O.M.T was a recipient of an iCASE studentship from the BBSRC (Reference BB/M015432/1)

ACR appropriateness criteria® nasal cavity and paranasal sinus cancers

The American College of Radiology (ACR) Appropriateness Criteria are evidence‐based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer‐reviewed journals and the application of well‐established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407–418, 2017Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136245/1/hed24639.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136245/2/hed24639_am.pd

Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial

Abstract Background Fluticasone furoate (FF) is a novel, once-daily inhaled corticosteroid (ICS) that has been shown to improve lung function vs. placebo in asthma patients. This study evaluated the efficacy and safety of FF 50 mcg compared with placebo in asthma patients uncontrolled by non-ICS therapy. Methods This 12-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study randomized 248 patients (aged ≥12 years) to once-daily FF 50 mcg administered via the ELLIPTA™a dry powder inhaler or placebo. The primary endpoint was change from baseline in pre-dose evening trough forced expiratory volume in one second (FEV1). Secondary endpoints were change from baseline in percentage of rescue-free 24-h periods (powered), evening and morning peak expiratory flow, symptom-free 24-h periods and withdrawals due to lack of efficacy. Other endpoints included Asthma Control Test™, Asthma Quality of Life Questionnaire and ELLIPTA ease of use questions. Safety was assessed throughout the study. Results There was a significant difference in evening trough FEV1 between FF 50 mcg and placebo (treatment difference: 120 mL; p = 0.012). There was also a significant difference in rescue-free 24-h periods (11.6%; p = 0.004) vs. placebo. There were numerically greater improvements with FF vs. placebo for all remaining secondary endpoints. The incidence of adverse events was lower with FF (31%) than with placebo (38%); few were treatment-related (FF 50 mcg: n = 1, <1%; placebo: n = 4, 3%). Conclusion FF 50 mcg once daily significantly improved FEV1 and percentage of rescue-free 24-h periods experienced over 12 weeks vs. placebo, and was well tolerated. Trial registration www.clinicaltrials.gov , registration number: NCT0143607

Proposing a Core Outcome Set for Physical Activity and Exercise Interventions in People With Rare Neurological Conditions.

Rare neurological conditions (RNCs) encompass a variety of diseases that differ in progression and symptoms but typically include muscle weakness, sensory and balance impairment and difficulty with coordinating voluntary movement. This can limit overall physical activity, so interventions to address this are recommended. The aim of this study was to agree a core outcome measurement set for physical activity interventions in people living with RNCs. We followed established guidelines to develop core outcome sets. Broad ranging discussions in a series of stakeholder workshops led to the consensus that (1) physical well-being; (2) psychological well-being and (3) participation in day-to-day activities should be evaluated in interventions. Recommendations were further informed by a scoping review of physical activity interventions for people living with RNCs. Nearly 200 outcome measures were identified from the review with a specific focus on activities or functions (e.g, on lower limb function, ability to perform daily tasks) but limited consideration of participation based outcomes (e.g., social interaction, work and leisure). Follow on searches identified two instruments that matched the priority areas: the Oxford Participation and Activities Questionnaire and the Sources of Self-Efficacy for Physical Activity. We propose these scales as measures to assess outcomes that are particularly relevant to assess when evaluating physical activity interventions mong people with RNCs. Validation work across rare neurological conditions is now required to inform application of this core outcome set in future clinical trials to facilitate syntheses of results and meta-analyses