Development of a comprehensive protein microarray for immunoglobulin E profiling in horses with severe asthma

Background: Severe asthma in horses, known as severe equine asthma (SEA), is a prevalent, performance-limiting disease associated with increased allergen-specific immunoglobulin E (IgE) against a range of environmental aeroallergens. Objective: To develop a protein microarray platform to profile IgE against a range of proven and novel environmental proteins in SEA-affected horses. Animals: Six SEA-affected and 6 clinically healthy Warmblood performance horses. Methods: Developed a protein microarray (n = 384) using protein extracts and purified proteins from a large number of families including pollen, bacteria, fungi, and arthropods associated with the horses, environment. Conditions were optimized and assessed for printing, incubation, immunolabeling, biological fluid source, concentration techniques, reproducibility, and specificity. Results: This method identified a number of novel allergens, while also identifying an association between SEA and pollen sensitization. Immunolabeling methods confirmed the accuracy of a commercially available mouse anti-horse IgE 3H10 source (R2 = 0.91). Biological fluid source evaluation indicated that sera and bronchoalveolar lavage fluid (BALF) yielded the same specific IgE profile (average R2 = 0.75). Amicon centrifugal filters were found to be the most efficient technique for concentrating BALF for IgE analysis at 40-fold. Overnight incubation maintained the same sensitization profile while increasing sensitivity. Reproducibility was demonstrated (R2 = 0.97), as was specificity using protein inhibition assays. Arthropods, fungi, and pollens showed the greatest discrimination for SEA. Conclusions and clinical importance: We have established that protein microarrays can be used for large-scale IgE mapping of allergens associated with the environment of horses. This technology provides a sound platform for specific diagnosis, management, and treatment of SEA

Experimental Signatures of Critically Balanced Turbulence in MAST

Beam Emission Spectroscopy (BES) measurements of ion-scale density fluctuations in the MAST tokamak are used to show that the turbulence correlation time, the drift time associated with ion temperature or density gradients, the particle (ion) streaming time along the magnetic field and the magnetic drift time are consistently comparable, suggesting a "critically balanced" turbulence determined by the local equilibrium. The resulting scalings of the poloidal and radial correlation lengths are derived and tested. The nonlinear time inferred from the density fluctuations is longer than the other times; its ratio to the correlation time scales as $\nu_{*i}^{-0.8\pm0.1}$, where $\nu_{*i}=$ ion collision rate/streaming rate. This is consistent with turbulent decorrelation being controlled by a zonal component, invisible to the BES, with an amplitude exceeding the drift waves' by $\sim \nu_{*i}^{-0.8}$.Comment: 6 pages, 4 figures, submitted to PR

Clients’ Perspectives of Meaningful Healthcare Relationships

The aim of this study was to increase understanding of how clients view meaningful relationships within the healthcare context and how clients respond to differences in approaches or expectations for a meaningful relationship

THE INFLUENCE OF CHANGES IN SPRINT ABlLlN ON THE SLED VELOCIN PROFILE DURING THE SKELETON START

Sprint times are key predictors of skeleton start petformance, but the effect of enhancing sprint ability on the development of sled velocity is unknown. Twelve well-trained skeleton athletes performed three dry-land push-starts and three 30-m sprints before and after 16 training weeks. Sled velocity profiles were characterised using three descriptors (pre-load velocity, pre-load distance and load effectiveness) and a sled acceleration index was used to evaluate performance. Increases in pre-load velocity and distance were related to improved sprint times. However, enhanced sprint ability did not guarantee a faster start as reductions in load effectiveness were also observed when higher velocities were attained. Coaches could supplement physical conditioning with load technique training to potentially improve the transfer of training-induced sled velocity increases across the loading phase

Electron scattering from molecules and molecular aggregates of biological relevance

In this Topical Review we survey the current state of the art in the study of low energy electron collisions with biologically relevant molecules and molecular clusters. We briefly describe the methods and techniques used in the investigation of these processes and summarise the results obtained so far for DNA constituents and their model compounds, amino acids, peptides and other biomolecules. The applications of the data obtained is briefly described as well as future required developments

Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimeticPeptide

Increased levels of neurotoxic amyloid-beta in the brain are a prominent feature of Alzheimer’s disease. FG-Loop (FGL), a neural cell adhesion molecule-derived peptide that corresponds to its second fibronectin type III module, has been shown to provide neuroprotection against a range of cellular insults. In the present study impairments in social recognition memory were seen 24 days after a 5 mg/15 µl amyloid-beta(25–35) injection into the right lateral ventricle of the young adult rat brain. This impairment was prevented if the animal was given a systemic treatment of FGL. Unbiased stereology was used to investigate the ability of FGL to alleviate the deleterious effects on CA1 pyramidal cells of the amyloid-beta(25–35) injection. NeuN, a neuronal marker (for nuclear staining) was used to identify pyramidal cells, and immunocytochemistry was also used to identify inactive glycogen synthase kinase 3beta (GSK3β) and to determine the effects of amyloid-beta(25–35) and FGL on the activation state of GSK3β, since active GSK3β has been shown to cause a range of AD pathologies. The cognitive deficits were not due to hippocampal atrophy as volume estimations of the entire hippocampus and its regions showed no significant loss, but amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 which was alleviated partially by FGL. However, FGL treatment without amyloid-beta was also found to cause a 40% decrease in CA1 pyramidal cells. The action of FGL may be due to inactivation of GSK3β, as an increased proportion of CA1 pyramidal neurons contained inactive GSK3β after FGL treatment. These data suggest that FGL, although potentially disruptive in nonpathological conditions, can be neuroprotective in disease-like conditions

Dynamical (e, 2e) Studies Using Tetrahydrofuran As a DNA Analog

Triple differential cross sections for the electron-impact ionization of the outer valence orbital of tetrahydrofuran have been measured using the (e, 2e) technique. The measurements have been performed with coplanar asymmetric kinematics, at an incident electron energy of 250 eV and at an ejected electron energy of 10 eV, over a range of momentum transfers. The experimental results are compared with theoretical calculations carried out using the molecular three-body distorted wave model. The results obtained are important for gaining an understanding of electron driven processes at a molecular level and for modeling energy deposition in living tissue

Isca, v1.0: a framework for the global modelling of the atmospheres of Earth and other planets at varying levels of complexity

This is the final version of the article. Available from EGU via the DOI in this record.The accepted author manuscript, published in Geoscientific Model Development Discussions, is in ORE: http://hdl.handle.net/10871/31579Isca is a framework for the idealized modelling of the global circulation of planetary atmospheres at varying levels of complexity and realism. The framework is an outgrowth of models from the Geophysical Fluid Dynamics Laboratory in Princeton, USA, designed for Earth's atmosphere, but it may readily be extended into other planetary regimes. Various forcing and radiation options are available, from dry, time invariant, Newtonian thermal relaxation to moist dynamics with radiative transfer. Options are available in the dry thermal relaxation scheme to account for the effects of obliquity and eccentricity (and so seasonality), different atmospheric optical depths and a surface mixed layer. An idealized grey radiation scheme, a two-band scheme, and a multiband scheme are also available, all with simple moist effects and astronomically based solar forcing. At the complex end of the spectrum the framework provides a direct connection to comprehensive atmospheric general circulation models. For Earth modelling, options include an aquaplanet and configurable continental outlines and topography. Continents may be defined by changing albedo, heat capacity, and evaporative parameters and/or by using a simple bucket hydrology model. Oceanic Q fluxes may be added to reproduce specified sea surface temperatures, with arbitrary continental distributions. Planetary atmospheres may be configured by changing planetary size and mass, solar forcing, atmospheric mass, radiation, and other parameters. Examples are given of various Earth configurations as well as a giant planet simulation, a slowly rotating terrestrial planet simulation, and tidally locked and other orbitally resonant exoplanet simulations. The underlying model is written in Fortran and may largely be configured with Python scripts. Python scripts are also used to run the model on different architectures, to archive the output, and for diagnostics, graphics, and post-processing. All of these features are publicly available in a Git-based repository.This work was funded by the Leverhulme Trust, NERC (grant NE/M006123/1), the Royal Society (Wolfson Foundation), EPSRC, the Newton Fund (CSSP project), and the Marie Curie Foundation

Isca, v1.0: a framework for the global modelling of the atmospheres of Earth and other planets at varying levels of complexity

This is the final version of the article. Available from EGU via the DOI in this record.The accepted author manuscript, published in Geoscientific Model Development Discussions, is in ORE: http://hdl.handle.net/10871/31579Isca is a framework for the idealized modelling of the global circulation of planetary atmospheres at varying levels of complexity and realism. The framework is an outgrowth of models from the Geophysical Fluid Dynamics Laboratory in Princeton, USA, designed for Earth's atmosphere, but it may readily be extended into other planetary regimes. Various forcing and radiation options are available, from dry, time invariant, Newtonian thermal relaxation to moist dynamics with radiative transfer. Options are available in the dry thermal relaxation scheme to account for the effects of obliquity and eccentricity (and so seasonality), different atmospheric optical depths and a surface mixed layer. An idealized grey radiation scheme, a two-band scheme, and a multiband scheme are also available, all with simple moist effects and astronomically based solar forcing. At the complex end of the spectrum the framework provides a direct connection to comprehensive atmospheric general circulation models. For Earth modelling, options include an aquaplanet and configurable continental outlines and topography. Continents may be defined by changing albedo, heat capacity, and evaporative parameters and/or by using a simple bucket hydrology model. Oceanic Q fluxes may be added to reproduce specified sea surface temperatures, with arbitrary continental distributions. Planetary atmospheres may be configured by changing planetary size and mass, solar forcing, atmospheric mass, radiation, and other parameters. Examples are given of various Earth configurations as well as a giant planet simulation, a slowly rotating terrestrial planet simulation, and tidally locked and other orbitally resonant exoplanet simulations. The underlying model is written in Fortran and may largely be configured with Python scripts. Python scripts are also used to run the model on different architectures, to archive the output, and for diagnostics, graphics, and post-processing. All of these features are publicly available in a Git-based repository.This work was funded by the Leverhulme Trust, NERC (grant NE/M006123/1), the Royal Society (Wolfson Foundation), EPSRC, the Newton Fund (CSSP project), and the Marie Curie Foundation