The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma

The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma

The Discovery of a Giant H-alpha Filament in NGC 7213

The nearby Seyfert galaxy NGC 7213 has been imaged in H-alpha and HI with the CTIO 1.5 m telescope and with the Australia Telescope Compact Array (ATCA), respectively. Optically NGC 7213 looks undisturbed and relatively featureless but the continuum-subtracted H-alpha image shows a 19 kpc long filament located approximately 18.6 kpc from the nucleus. The H-alpha filament could be neutral gas photo-ionized by the active nucleus, as has been suggested for the Seyfert galaxy NGC 5252, or shock-ionized by a jet interacting with the surrounding HI, as has been suggested for the radio galaxy PKS 2240-41. The HI map reveals NGC 7213 to be a highly disturbed system suggesting a past merging event.Comment: 14 pages including 4 figures and 1 table. Figures 1-4 are in jpeg format; Better quality images can be retrieved in postscript format at ftp://charon.nmsu.edu/pub/shameed/ ; Accepted for publication in ApJ Letter

Feeling controlled or being in control? Apps for self-management among older people with neurological disability

Purpose: The aim of this paper was to describe how people living with a neurological disability such as multiple sclerosis, Parkinson’s disease and stroke reason regarding using apps to facilitate self-management in everyday life. Material and methods: A qualitative research approach with a focus group methodology was used. The sample comprised 16 participants, 11 men and 5 women, with an average age of 64 years (ranging from 51–80 years). Six participants were diagnosed with multiple sclerosis, six with Parkinson’s disease and four with stroke. Data were analyzed using thematic analysis, which is a method for identifying, analyzing and reporting patterns. Results: The results formed two themes. The first theme “using apps to have control of my health” comprises two subthemes; “monitor and take responsibility for a healthy lifestyle” and “compensate to facilitate everyday life”. The second theme “using the app as a tool and means for communication” also comprised two subthemes; “dare to trust the app” and “feeling safe when sharing information with health care professionals”. Conclusions: The use of apps put increased responsibility on the person and had the possibility to make them more involved in their own care. The use of an app can facilitate a healthy lifestyle and help to monitor disease-specific symptoms. In order to be able to use apps for communication with the health care sector legislation and safety issues need to be considered. Implications for rehabilitation Apps can be used for self-management if they are safe and can be trusted. People with neurological disabilities want to be involved in their healthcare and needs to be addressed by health care professionals. The use of apps grasp over a wide variety of areas this is something that may be considered in health care and something that can be addressed by interdisciplinary approaches. Ordinary health-oriented apps and disease-specific apps were used differently and for different purposes

Radio Continuum Jet in NGC 7479

The barred galaxy NGC 7479 hosts a remarkable jet-like radio continuum feature: bright, 12-kpc long in projection, and hosting an aligned magnetic field. The degree of polarization is 6%-8% along the jet, and remarkably constant, which is consistent with helical field models. The radio brightness of the jet suggests strong interaction with the ISM and hence a location near the disk plane. We observed NGC 7479 at four wavelengths with the VLA and Effelsberg radio telescopes. The equipartition strength is 35-40 micro-G for the total and >10 micro-G for the ordered magnetic field in the jet. The jet acts as a bright, polarized background. Faraday rotation between 3.5 and 6 cm and depolarization between 6 and 22 cm can be explained by magneto-ionic gas in front of the jet, with thermal electron densities of ~0.06 cm**(-3) in the bar and ~0.03 cm**(-3) outside the bar. The regular magnetic field along the bar points toward the nucleus on both sides. The regular field in the disk reveals multiple reversals, probably consisting of field loops stretched by a shearing gas flow in the bar. The projection of the jet bending in the sky plane is in the sense opposite to that of the underlying stellar and gaseous spiral structure. The bending in 3-D is most easily explained as a precessing jet, with an age less than 10**6 years. Our observations are consistent with very recent triggering, possibly by a minor merger. NGC 7479 provides a unique opportunity to study interaction-triggered 15-kpc scale radio jets within a spiral galaxy.Comment: 18 pages, 21 figures, accepted for publication in the Astrophysical Journa

The Radio Properties of Composite LINER/HII Galaxies

Arcsec-resolution VLA observations -- newly obtained as well as published -- of 40 nearby galaxies are discussed, completing a study of the radio properties of a magnitude-limited sample of nearby galaxies of the composite LINER/HII type. Our results reveal an overall detection rate of at least 25% AGN candidates among these composite sources. The general properties of these AGN candidates, as compared to non-AGN composite sources and HII galaxies, are discussed.Comment: Accepted for publication in ApJ

The helminth product, ES-62, protects against airway inflammation by resetting the Th cell phenotype

We previously demonstrated inhibition of ovalbumin (OVA)-induced allergic airway hyper-responsiveness in the mouse using ES-62, a phosphorylcholine-containing glycoprotein secreted by the filarial nematode, Acanthocheilonema viteae. This inhibition correlated with ES-62-induced mast cell desensitisation, although the degree to which this reflected direct targeting of mast cells remained unclear as suppression of the Th2 phenotype of the inflammatory response, as measured by eosinophilia and IL-4 levels in the lungs, was also observed. We now show that inhibition of the lung Th2 phenotype is reflected in ex vivo analyses of draining lymph node recall cultures and accompanied by a decrease in the serum levels of total and OVA-specific IgE. Moreover, ES-62 also suppresses the lung infiltration by neutrophils that is associated with severe asthma and is generally refractory to conventional anti-inflammatory therapies, including steroids. Protection against Th2-associated airway inflammation does not reflect induction of regulatory T cell (Treg) responses (there is no increased IL-10 or Foxp3 expression) but rather a switch in polarisation towards increased T-bet expression and IFNγ production. This ES-62-driven switch in the Th1/Th2 balance is accompanied by decreased IL-17 responses, a finding in line with reports that IFNγ and IL-17 are counter-regulatory. Consistent with ES-62 mediating its effects via IFNγ-mediated suppression of pathogenic Th2/Th17 responses, we found that neutralising anti-IFNγ antibodies blocked protection against airway inflammation in terms of pro-inflammatory cell infiltration, particularly by neutrophils and lung pathology. Collectively, these studies indicate that ES-62, or more likely small molecule analogues, could have therapeutic potential in asthma, in particular for those subtypes of patients (e.g. smokers, steroid-resistant) who are refractory to current treatments

The scalar gluonium correlator: large-beta_0 and beyond

The investigation of the scalar gluonium correlator is interesting because it carries the quantum numbers of the vacuum and the relevant hadronic current is related to the anomalous trace of the QCD energy-momentum tensor in the chiral limit. After reviewing the purely perturbative corrections known up to next-next-to-leading order, the behaviour of the correlator is studied to all orders by means of the large-beta_0 approximation. Similar to the QCD Adler function, the large-order behaviour is governed by the leading ultraviolet renormalon pole. The structure of infrared renormalon poles, being related to the operator product expansion are also discussed, as well as a low-energy theorem for the correlator that provides a relation to the renormalisation group invariant gluon condensate, and the vacuum matrix element of the trace of the QCD energy-momentum tensor.Comment: 14 pages, references added, discussion of IR renormalon pole at u=3 extended, similar version to appear in JHE

Axial Vector JPC=1++J^{PC}=1^{++} Charmonium and Bottomonium Hybrid Mass Predictions with QCD Sum-Rules

Axial vector $(J^{PC}=1^{++})$ charmonium and bottomonium hybrid masses are determined via QCD Laplace sum-rules. Previous sum-rule studies in this channel did not incorporate the dimension-six gluon condensate, which has been shown to be important for $1^{--}$ and $0^{-+}$ heavy quark hybrids. An updated analysis of axial vector charmonium and bottomonium hybrids is presented, including the effects of the dimension-six gluon condensate. The axial vector charmonium and bottomonium hybrid masses are predicted to be 5.13 GeV and 11.32 GeV, respectively. We discuss the implications of this result for the charmonium-like XYZ states and the charmonium hybrid multiplet structure observed in recent lattice calculations.Comment: 10 pages, 7 figures. Updated to match published versio

Brittle-Ductile Deformation and Tensile Rupture of Dome Lava During Inflation at Santiaguito, Guatemala

Gas‐and‐ash explosions at the Santiaguito dome complex, Guatemala, commonly occur through arcuate fractures, following a 5‐ to 6‐min period of inflation observed in long‐period seismic signals. Observation of active faults across the dome suggests a strong shear component, but as fault propagation generally proceeds through the coalescence of tensile fractures, we surmise that explosive eruptions require tensile rupture. Here, we assess the effects of temperature and strain rate on fracture propagation and the tensile strength of Santiaguito dome lavas. Indirect tensile tests were conducted on samples with a porosity range of 3–30% and over diametral displacement rates of 0.04, 0.004, and 0.0004 mm/s. At room temperature, the tensile strength of dome rock is rate independent (within the range tested) and inversely proportional to the porosity of the material. At eruptive temperatures we observe an increasingly ductile response at either higher temperature or lower displacement rate, where ductile deformation is manifest by a reduction in loading rate during constant deformation rate tests, resulting in slow tearing, viscous flow, and pervasive damage. We propose a method to conduct indirect tensile tests under volcanic conditions using a modification of the Brazilian disc testing protocol and use brittleness indices to classify deformation modes across the brittle‐ductile transition. We show that a degree of ductile damage is inevitable in the lava core during explosions at the Santiaguito dome complex and discuss how strain leading to rupture controls fracture geometry, which would impact gas pressure release or buildup and regulate explosive activity