Function of monocytes in chronic HCV infection: Role for IL-10 and interferon

Hepatitis C virus (HCV) establishes persistent infection in about 80% of the infected individuals. The symptoms are initially mild in those persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Up to 20% of infected individuals may develop complications, including cirrhosis, liver failure, or hepatocellular carcinoma [3]. HCV infection is now the leading indication for liver transplantation in the United States and Europe

Understanding IFNλ in rheumatoid arthritis

Unraveling the mechanisms underlying the inflammatory response in rheumatoid arthritis is crucial in order to better understand the disease and to develop novel therapeutic approaches. Although the effect of type I interferons on fibroblasts and in the context of rheumatoid arthritis has been described for some time, little is known on the effects of the type III interferons, also known as IFNλ. In a previous issue, Xu and colleagues demonstrate that one of the members of the IFNλ family, IFNλ1, enhances Toll-like receptor expression and consequently promotes the production of proinflammatory cytokines known to be involved in initiating and maintaining the inflammatory responses in rheumatoid arthritis

Cycling Stem Cells Are Radioresistant and Regenerate the Intestine.

A certain number of epithelial cells in intestinal crypts are DNA damage resistant and contribute to regeneration. However, the cellular mechanism underlying intestinal regeneration remains unclear. Using lineage tracing, we show that cells marked by an Msi1 reporter (Msi1+) are right above Lgr5high cells in intestinal crypts and exhibit DNA damage resistance. Single-cell RNA sequencing reveals that the Msi1+ cells are heterogeneous with the majority being intestinal stem cells (ISCs). The DNA damage-resistant subpopulation of Msi1+ cells is characterized by low-to-negative Lgr5 expression and is more rapidly cycling than Lgr5high radiosensitive crypt base columnar stem cells (CBCs). This enables an efficient repopulation of the intestinal epithelium at early stage when Lgr5high cells are not emerging. Furthermore, relative to CBCs, Msi1+ cells preferentially produce Paneth cells during homeostasis and upon radiation repair. Together, we demonstrate that the DNA damage-resistant Msi1+ cells are cycling ISCs that maintain and regenerate the intestinal epithelium

The Knee of the Cosmic Hydrogen and Helium Spectrum below 1 PeV Measured by ARGO-YBJ and a Cherenkov Telescope of LHAASO

The measurement of cosmic ray energy spectra, in particular for individual species, is an essential approach in finding their origin. Locating the "knees" of the spectra is an important part of the approach and has yet to be achieved. Here we report a measurement of the mixed Hydrogen and Helium spectrum using the combination of the ARGO-YBJ experiment and of a prototype Cherenkov telescope for the LHAASO experiment. A knee feature at 640+/-87 TeV, with a clear steepening of the spectrum, is observed. This gives fundamental inputs to galactic cosmic ray acceleration models

4.5 years multi-wavelength observations of Mrk 421 during the ARGO-YBJ and Fermi common operation time

We report on the extensive multi-wavelength observations of the blazar Markarian 421 (Mrk 421) covering radio to gamma-rays, during the 4.5 year period of ARGO-YBJ and Fermi common operation time, from August 2008 to February 2013. In particular, thanks to the ARGO-YBJ and Fermi data, the whole energy range from 100 MeV to 10 TeV is covered without any gap. In the observation period, Mrk 421 showed both low and high activity states at all wavebands. The correlations among flux variations in different wavebands were analyzed. Seven large flares, including five X-ray flares and two GeV gamma-ray flares with variable durations (3-58 days), and one X-ray outburst phase were identified and used to investigate the variation of the spectral energy distribution with respect to a relative quiescent phase. During the outburst phase and the seven flaring episodes, the peak energy in X-rays is observed to increase from sub-keV to few keV. The TeV gamma-ray flux increases up to 0.9-7.2 times the flux of the Crab Nebula. The behavior of GeV gamma-rays is found to vary depending on the flare, a feature that leads us to classify flares into three groups according to the GeV flux variation. Finally, the one-zone synchrotron self-Compton model was adopted to describe the emission spectra. Two out of three groups can be satisfactorily described using injected electrons with a power-law spectral index around 2.2, as expected from relativistic diffuse shock acceleration, whereas the remaining group requires a harder injected spectrum. The underlying physical mechanisms responsible for different groups may be related to the acceleration process or to the environment properties.Comment: 17 pages, 9 figures, 5 tables, Accepted for publication in ApJ

The ARGO-YBJ Experiment Progresses and Future Extension

Gamma ray source detection above 30TeV is an encouraging approach for finding galactic cosmic ray origins. All sky survey for gamma ray sources using wide field of view detector is essential for population accumulation for various types of sources above 100GeV. To target the goals, the ARGO-YBJ experiment has been established. Significant progresses have been made in the experiment. A large air shower detector array in an area of 1km2 is proposed to boost the sensitivity. Hybrid detection with multi-techniques will allow a good discrimination between different types of primary particles, including photons and protons, thus enable an energy spectrum measurement for individual specie. Fluorescence light detector array will extend the spectrum measurement above 100PeV where the second knee is located. An energy scale determined by balloon experiments at 10TeV will be propagated to ultra high energy cosmic ray experiments

The cosmic ray proton plus helium energy spectrum measured by the ARGO-YBJ experiment in the energy range 3-300 TeV

The ARGO-YBJ experiment is a full-coverage air shower detector located at the Yangbajing Cosmic Ray Observatory (Tibet, People's Republic of China, 4300 m a.s.l.). The high altitude, combined with the full-coverage technique, allows the detection of extensive air showers in a wide energy range and offer the possibility of measuring the cosmic ray proton plus helium spectrum down to the TeV region, where direct balloon/space-borne measurements are available. The detector has been in stable data taking in its full configuration from November 2007 to February 2013. In this paper the measurement of the cosmic ray proton plus helium energy spectrum is presented in the region 3-300 TeV by analyzing the full collected data sample. The resulting spectral index is $\gamma = -2.64 \pm 0.01$. These results demonstrate the possibility of performing an accurate measurement of the spectrum of light elements with a ground based air shower detector.Comment: 18 pages, 8 figures, preprint submitted to Phys. Rev.

EAS age determination from the study of the lateral distribution of charged particles near the shower axis with the ARGO-YBJ experiment

The ARGO-YBJ experiment, a full coverage extensive air shower (EAS) detector located at high altitude (4300 m a.s.l.) in Tibet, China, has smoothly taken data, with very high stability, since November 2007 to the beginning of 2013. The array consisted of a carpet of about 7000 m$^2$ Resistive Plate Chambers (RPCs) operated in streamer mode and equipped with both digital and analog readout, providing the measurement of particle densities up to few particles per cm$^2$. The unique detector features (full coverage, readout granularity, wide dynamic range, etc) and location (very high altitude) allowed a detailed study of the lateral density profile of charged particles at ground very close to the shower axis and its description by a proper lateral distribution function (LDF). In particular, the information collected in the first 10 m from the shower axis have been shown to provide a very effective tool for the determination of the shower development stage ("age") in the energy range 50 TeV - 10 PeV. The sensitivity of the age parameter to the mass composition of primary Cosmic Rays is also discussed

Gamma ray flares from Mrk421 in 2008 observed with the ARGO-YBJ detector

In 2008 the blazar Markarian 421 entered a very active phase and was one of the brightest sources in the sky at TeV energies, showing frequent flaring episodes. Using the data of ARGO-YBJ, a full coverage air shower detector located at Yangbajing (4300 m a.s.l., Tibet, China), we monitored the source at gamma ray energies E > 0.3 TeV during the whole year. The observed flux was variable, with the strongest flares in March and June, in correlation with X-ray enhanced activity. While during specific episodes the TeV flux could be several times larger than the Crab Nebula one, the average emission from day 41 to 180 was almost twice the Crab level, with an integral flux of (3.6 +-0.6) 10^-11 photons cm^-2 s^-1 for energies E > 1 TeV, and decreased afterwards. This paper concentrates on the flares occurred in the first half of June. This period has been deeply studied from optical to 100 MeV gamma rays, and partially up to TeV energies, since the moonlight hampered the Cherenkov telescope observations during the most intense part of the emission. Our data complete these observations, with the detection of a signal with a statistical significance of 3.8 standard deviations on June 11-13, corresponding to a gamma ray flux about 6 times larger than the Crab one above 1 TeV. The reconstructed differential spectrum, corrected for the intergalactic absorption, can be represented by a power law with an index alpha = -2.1 extending up to several TeV. The spectrum slope is fully consistent with previous observations reporting a correlation between the flux and the spectral index, suggesting that this property is maintained in different epochs and characterizes the source emission processes.Comment: Accepted for publication on ApJ

Observation of TeV gamma rays from the Cygnus region with the ARGO-YBJ experiment

We report the observation of TeV gamma-rays from the Cygnus region using the ARGO-YBJ data collected from 2007 November to 2011 August. Several TeV sources are located in this region including the two bright extended MGRO J2019+37 and MGRO J2031+41. According to the Milagro data set, at 20 TeV MGRO J2019+37 is the most significant source apart from the Crab Nebula. No signal from MGRO J2019+37 is detected by the ARGO-YBJ experiment, and the derived flux upper limits at 90% confidence level for all the events above 600 GeV with medium energy of 3 TeV are lower than the Milagro flux, implying that the source might be variable and hard to be identified as a pulsar wind nebula. The only statistically significant (6.4 standard deviations) gamma-ray signal is found from MGRO J2031+41, with a flux consistent with the measurement by Milagro.Comment: 14 pages, 4 figure