Background Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with ...cystic fibrosis (CF)–associated lung disease remains unclear. Objective The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Methods Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Results Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Conclusion Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease.
A time projection chamber (TPC) can be used to measure the polarization of gamma rays with excellent angular precision and sensitivity in the MeV-GeV energy range through the conversion of photons to ...e+e− pairs. The Hermetic ARgon POlarimeter (HARPO) prototype was built to demonstrate this concept. It was recently tested in the polarized photon beam at the NewSUBARU facility in Japan. We present this data-taking run, which demonstrated the excellent performance of the HARPO TPC.
Abstract
We present the results of variability power spectral density (PSD) analysis using multiwavelength radio to GeV
γ
-ray light curves covering timescales of decades/years to days/minutes for ...the blazars 3C 279 and PKS 1510−089. The PSDs are modeled as single power laws, and the best-fit spectral shape is derived using the “power spectral response” method. With more than 10 yr of data obtained with weekly/daily sampling intervals, most of the PSDs cover ∼2–4 decades in temporal frequency; moreover, in the optical band, the PSDs cover ∼6 decades for 3C 279 due to the availability of intranight light curves. Our main results are the following: (1) on timescales ranging from decades to days, the synchrotron and the inverse-Compton spectral components, in general, exhibit red-noise (slope ∼2) and flicker-noise (slope ∼1) type variability, respectively; (2) the slopes of
γ
-ray variability PSDs obtained using a 3 hr integration bin and 3 weeks total duration exhibit a range between ∼1.4 and ∼2.0 (mean slope = 1.60 ± 0.70), consistent within errors with the slope on longer timescales; (3) comparisons of fractional variability indicate more power on timescales ≤100 days at
γ
-ray frequencies compared to longer wavelengths, in general (except between the
γ
-ray and optical wavelengths for PKS 1510−089); (4) the normalization of intranight optical PSDs for 3C 279 appears to be a simple extrapolation from longer timescales, indicating a continuous (single) process driving the variability at optical wavelengths; and (5) the emission at optical/infrared wavelengths may involve a combination of disk and jet processes for PKS 1510−089.
Blazars are known for their variability on a wide range of timescales at all wavelengths. Most studies of TeV gamma-ray blazars focus on short timescales, especially during flares. With a decade of ...observations from the Fermi-LAT and VERITAS, we present an extensive study of the long-term multiwavelength radio-to-gamma-ray flux-density variability, with the addition of a couple of short-time radio-structure and optical polarization observations of the blazar 1ES 1215+303 (z = 0.130), with a focus on its gamma-ray emission from 100 MeV to 30 TeV. Multiple strong GeV gamma-ray flares, a long-term increase in the gamma-ray and optical flux baseline, and a linear correlation between these two bands are observed over the ten-year period. Typical HBL behaviors are identified in the radio morphology and broadband spectrum of the source. Three stationary features in the innermost jet are resolved by Very Long Baseline Array at 43.1, 22.2, and 15.3 GHz. We employ a two-component synchrotron self-Compton model to describe different flux states of the source, including the epoch during which an extreme shift in energy of the synchrotron peak frequency from infrared to soft X-rays is observed.
The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected ...individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the
gene. Of interest, this is the only described HPS type 1 patient with two different (compound heterozygote) splice site variants in
In addition to detailing a novel genetic result and outlining the progressive clinical course of disease in this case, we discuss the management of HPS, the prognostic value of subtype analysis and the technical difficulties relating to transplantation in the case of HPS-associated advanced pulmonary fibrosis. This case also illustrates the concept of lung phenocopy relationships and the potential for elucidating the pathogenesis of more common pulmonary disorders by studying genetic diseases that result in similar phenotypes. Furthermore, it re-emphasises the importance of the patient voice, particularly with regard to complex diagnoses and rare diseases.
This chapter outlines the general principles for the detection and characterisation of high-energy \(\gamma\)-ray photons in the energy range from MeV to GeV. Applications of these fundamental ...photon-matter interaction processes to the construction of instruments for \(\gamma\)-ray astronomy are described, including a short review of past and present realisations of telescopes. The constraints encountered in operating telescopes on high-altitude balloon and satellite platforms are described in the context of the strong instrumental background from cosmic rays as well as astrophysical sources. The basic telescope concepts start from the general collimator aperture in the MeV range over its improvements through coded-mask and Compton telescopes, to pair production telescopes in the GeV range. Other apertures as well as understanding the measurement principles of \(\gamma\)-ray astrophysics from simulations to calibrations are also provided.
We present here the results of the analysis of the $\gamma$-ray blazar, 1ES
1215+303, over a 10-year period, from 2008 to 2017, measured at high energies
(HE; 200 MeV $< E <$ 100 GeV) by the Fermi ...Large Area Telescope (LAT) and at
very high energies (VHE; $E >$ 100 GeV) by Fermi-LAT and VERITAS. This is the
longest temporal study of this high-frequency-peaked BL Lac object (HBL) at
$\gamma$-ray energies to date. The spectrum follows a log parabola over this
time period, and its HE and VHE spectra are well-connected. Its flux is
sufficiently strong at HE to allow us to bin the Fermi-LAT data in 3-day
intervals, enabling us to investigate the temporal evolution of the flux in
unprecedented detail. Several flaring episodes were detected and evidence for
an overall trend of increasing flux over the span of the 10 years was observed.
These light curves, in addition to the spectra, are presented. This unique data
set will help us to advance our understanding of the underlying physical
processes in blazar jets.
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