5,925 research outputs found
The drug efflux pump Pgp1 in pro-inflammatory lymphocytes is a target for novel treatment strategies in COPD
Extent: 8 p.BACKGROUND: Pro-inflammatory/cytotoxic T cells (IFNγ, TNFα, granzyme B+) are increased in the peripheral circulation in COPD. NKT-like and NK cells are effector lymphocytes that we have also shown to be major sources of pro-inflammatory cytokines and granzymes. P-glycoprotein 1 (Pgp1) is a transmembrane efflux pump well characterised in drug resistant cancer cells. We hypothesized that Pgp1 would be increased in peripheral blood T, NKT-like and NK cells in patients with COPD, and that this would be accompanied by increased expression of IFNγ, TNFα and granzyme B. We further hypothesized that treatment with cyclosporine A, a Pgp1 inhibitor, would render cells more sensitive to treatment with corticosteroids. METHODS: Pgp1, granzyme B, IFNγ and TNFα expression were measured in peripheral blood T, NK and NKT-like cells from COPD patients and control subjects (± cyclosporine A and prednisolone) following in vitro stimulation and results correlated with uptake of efflux dye Calcein-AM using flow cytometry. RESULTS: There was increased Pgp1 expression by peripheral blood T, NKT-like and NK cells co-expressing IFNγ, TNFα and granzyme B in COPD patients compared with controls (e.g. %IFNγ/Pgp1 T, NKT-like, NK for COPD (Control): 25(6), 54(27), 39(23)). There was an inverse correlation between Pgp1 expression and Calcein-AM uptake. Treatment with 2.5 ng/ml cylosporin A and10-6 M prednisolone resulted in synergistic inhibition of pro-inflammatory cytokines in Pgp1 + cells (p < 0.05 for all). CONCLUSIONS: Treatment strategies that target Pgp1 in T, NKT-like and NK cells may reduce systemic inflammatory mediators in COPD and improve patient morbidity.Greg Hodge, Mark Holmes, Hubertus Jersmann, Paul N. Reynolds and Sandra Hodg
Landscapes and Fragilities
The concept of fragility provides a possibility to rank different supercooled
liquids on the basis of the temperature dependence of dynamic and/or
thermodynamic quantities. We recall here the definitions of kinetic and
thermodynamic fragility proposed in the last years and discuss their
interrelations. At the same time we analyze some recently introduced models for
the statistical properties of the potential energy landscape. Building on the
Adam-Gibbs relation, which connects structural relaxation times to
configurational entropy, we analyze the relation between statistical properties
of the landscape and fragility. We call attention to the fact that the
knowledge of number, energy depth and shape of the basins of the potential
energy landscape may not be sufficient for predicting fragility. Finally, we
discuss two different possibilities for generating strong behavior.Comment: 17 pages, 10 figures; accepted version, minor correction
Monitoring the Low-Energy Gamma-Ray Sky Using Earth Occultation with GLAST GBM
Long term all-sky monitoring of the 20 keV – 2 MeV gamma-ray sky using the Earth occultation technique was demonstrated by the BATSE instrument on the Compton Gamma Ray Observatory. The principles and techniques used for the development of an end-to-end earth occultation data analysis system for BATSE can be extended to the GLAST Burst Monitor (GBM), resulting in multiband light curves and time-resolved spectra in the energy range 8 keV to above 1 MeV for known gamma-ray sources and transient outbursts, as well as the discovery of new sources of gamma-ray emission. In this paper we describe the application of the technique to the GBM. We also present the expected sensitivity for the GBM
Changes in mass balance of South Cascade Glacier, North Cascades, 1959 to 1994
EXTRACT (SEE PDF FOR FULL ABSTRACT):
Annual, winter, and summer mass balance measurements at South Cascade Glacier in the North Cascade Mountains of Washington State constitute a continuous time series 36 years long, from 1959 to 1994. ... The long-term trends at South Cascade Glacier are decreased winter accumulation and increased summer ablation, neither of which is conducive to glacier growth, so the trend in the Pacific Northwest is clearly away from an ice-age type of climate at the current time. The data also demonstrate that a glaciologically significant long-term change in snow precipitation can occur rapidly, in as short an interval as 1 year, much more rapidly than changes in temperature
The Stellar Populations of NGC 3109: Another Dwarf Irregular Galaxy with a Population II Stellar Halo
We have obtained V and I-band photometry for about 17500 stars in the field
of the dwarf irregular galaxy NGC3109, located in the outskirts of the Local
Group. The photometry allows us to study the stellar populations present inside
and outside the disk of this galaxy. From the VI color-magnitude diagram we
infer metallicities and ages for the stellar populations in the main body and
in the halo of NGC3109. The stars in the disk of this galaxy have a wide
variety of ages, including very young stars with approximately 10^7 yr. Our
main result is to establish the presence of a halo consisting of population II
stars, extending out to about 4.5 arcmin (or 1.8 kpc) above and below the plane
of this galaxy. For these old stars we derive an age of > 10 Gyr and a
metallicity of [Fe/H] = -1.8 +/- 0.2. We construct a deep luminosity function,
obtaining an accurate distance modulus (m-M)_0 = 25.62 +/- 0.1 for this galaxy
based on the I-magnitude of the red giant branch (RGB) tip and adopting E(V-I)
= 0.05.Comment: Accepted for publication in the Astronomical Journal 23 pages, latex,
12 Figures (Fig 1 not available in electronic format
Update and clinical utility of the LenSx femtosecond laser in cataract surgery
� 2016 Roberts et al. The introduction of femtosecond lasers to cataract surgery has been the major disruptive technology introduced into ophthalmic surgery in the last decade. Femtosecond laser cataract surgery (FLACS) integrates high-resolution anterior segment imaging with a femtosecond laser allowing key steps of cataract surgery to be performed with computer-guided laser accuracy, precision, and reproducibility. Since the introduction of FLACS, there have been significant advances in laser software and hardware as well as surgeon experience, with over 250 articles published in the peer-reviewed literature. This review examines the published evidence relating to the LenSx platform and discusses surgical techniques, indications, safety, and clinical results
Earth Occultation Imaging of the Low Energy Gamma-Ray Sky with GBM
The Earth Occultation Technique (EOT) has been applied to Fermi's Gamma-ray
Burst Monitor (GBM) to perform all-sky monitoring for a predetermined catalog
of hard X-ray/soft gamma-ray sources. In order to search for sources not in the
catalog, thus completing the catalog and reducing a source of systematic error
in EOT, an imaging method has been developed -- Imaging with a Differential
filter using the Earth Occultation Method (IDEOM). IDEOM is a tomographic
imaging method that takes advantage of the orbital precession of the Fermi
satellite. Using IDEOM, all-sky reconstructions have been generated for ~sim 4
years of GBM data in the 12-50 keV, 50-100 keV and 100-300 keV energy bands in
search of sources otherwise unmodeled by the GBM occultation analysis. IDEOM
analysis resulted in the detection of 57 sources in the 12-50 keV energy band,
23 sources in the 50-100 keV energy band, and 7 sources in the 100-300 keV
energy band. Seventeen sources were not present in the original GBM-EOT catalog
and have now been added. We also present the first joined averaged spectra for
four persistent sources detected by GBM using EOT and by the Large Area
Telescope (LAT) on Fermi: NGC 1275, 3C 273, Cen A, and the Crab
The Glass Transition Temperature of Water: A Simulation Study
We report a computer simulation study of the glass transition for water. To
mimic the difference between standard and hyperquenched glass, we generate
glassy configurations with different cooling rates and calculate the
dependence of the specific heat on heating. The absence of crystallization
phenomena allows us, for properly annealed samples, to detect in the specific
heat the simultaneous presence of a weak pre-peak (``shadow transition''), and
an intense glass transition peak at higher temperature.
We discuss the implications for the currently debated value of the glass
transition temperature of water. We also compare our simulation results with
the Tool-Narayanaswamy-Moynihan phenomenological model.Comment: submitted to Phys. Re
An HST/WFPC2 Survey of Bright Young Clusters in M31 III. Structural Parameters
Surface brightness profiles for 23 M31 star clusters were measured using
images from the Wide Field Planetary Camera 2 on the Hubble Space Telescope,
and fit to two types of models to determine the clusters' structural
properties. The clusters are primarily young (~10^8 yr) and massive (~10^4.5
solar masses), with median half-light radius 7 pc and dissolution times of a
few Gyr. The properties of the M31 clusters are comparable to those of clusters
of similar age in the Magellanic Clouds. Simulated star clusters are used to
derive a conversion from statistical measures of cluster size to half-light
radius so that the extragalactic clusters can be compared to young massive
clusters in the Milky Way. All three sets of star clusters fall approximately
on the same age-size relation. The young M31 clusters are expected to dissolve
within a few Gyr and will not survive to become old, globular clusters.
However, they do appear to follow the same fundamental plane relations as old
clusters; if confirmed with velocity dispersion measurements, this would be a
strong indication that the star cluster fundamental plane reflects universal
cluster formation conditions.Comment: AJ in press; 37 pages, 12 figure
The Absence of Extra-Tidal Structure in the Sculptor Dwarf Spheroidal Galaxy
The results of a wide-field survey of the Sculptor dwarf spheroidal galaxy
are presented. Our aims were to obtain an accurate map of the outer structure
of Sculptor, and to determine the level of interaction between this system and
the Galaxy. Photometry was obtained in two colours down to the magnitude limits
of V=20 and I=19, covering a 3.1 times 3.1 square deg area centred on Sculptor.
The resulting colour-magnitude data were used as a mask to select candidate
horizontal branch and red giant branch stars for this system. Previous work has
shown that the red horizontal branch (HB) stars are more concentrated than the
blue HB stars. We have determined the radial distributions of these two
populations and show that the overall Sculptor density profile is well
described by a two component model based on a combination of these radial
distributions. Additionally, spectra of the Ca ii triplet region were obtained
for over 700 candidate red giant stars over the 10 square deg region using the
2dF instrument on the Anglo-Australian Telescope. These spectra were used to
remove foreground Galactic stars based on radial velocity and Ca ii triplet
strength. The final list of Sculptor members contained 148 stars, seven of
which are located beyond the nominal tidal radius. Both the photometric and
spectroscopic datasets indicate no significant extra-tidal structure. These
results support at most a mild level of interaction between this system and the
Galaxy, and we have measured an upper mass limit for extra-tidal material to be
2.3 +/- 0.6% of the Sculptor luminous mass. This lack of tidal interaction
indicates that previous velocity dispersion measurements (and hence the amount
of dark matter detected) in this system are not strongly influenced by the
Galactic tidal field.Comment: 53 pages, 23 figures. Accepted for publication in the Astronomical
Journal. Some figures are reduced in size, and a full version is available
at: ftp://ftp.mso.anu.edu.au/pub/coleman/sculptor.pd
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