Cellular Immunity Confers Transient Protection in Experimental Buruli Ulcer following BCG or Mycolactone-Negative Mycobacterium ulcerans Vaccination

BACKGROUND: Buruli ulcer (BU) is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-gamma T cell response in the draining lymph node (DLN). BCG vaccination also resulted in cell-mediated immunity (CMI) in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-gamma and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised

Measurement of the Extragalactic Background Light using MAGIC and Fermi-LAT gamma-ray observations of blazars up to z = 1

We present a measurement of the extragalactic background light (EBL) based on a joint likelihood analysis of 32 gamma-ray spectra for 12 blazars in the redshift range z = 0.03 to 0.944, obtained by the MAGIC telescopes and Fermi-LAT. The EBL is the part of the diffuse extragalactic radiation spanning the ultraviolet, visible and infrared bands. Major contributors to the EBL are the light emitted by stars through the history of the universe, and the fraction of it which was absorbed by dust in galaxies and re-emitted at longer wavelengths. The EBL can be studied indirectly through its effect on very-high energy photons that are emitted by cosmic sources and absorbed via photon-photon interactions during their propagation across cosmological distances. We obtain estimates of the EBL density in good agreement with state-of-the-art models of the EBL production and evolution. The 1-sigma upper bounds, including systematic uncertainties, are between 13% and 23% above the nominal EBL density in the models. No anomaly in the expected transparency of the universe to gamma rays is observed in any range of optical depth.We also perform a wavelength-resolved EBL determination, which results in a hint of an excess of EBL in the 0.18 - 0.62 $\mu$m range relative to the studied models, yet compatible with them within systematics.Comment: Accepted by MNRA

Monitoring of the radio galaxy M87 during a low emission state from 2012 to 2015 with MAGIC

M87 is one of the closest (z=0.00436) extragalactic sources emitting at very-high-energies (VHE, E > 100 GeV). The aim of this work is to locate the region of the VHE gamma-ray emission and to describe the observed broadband spectral energy distribution (SED) during the low VHE gamma-ray state. The data from M87 collected between 2012 and 2015 as part of a MAGIC monitoring programme are analysed and combined with multi-wavelength data from Fermi-LAT, Chandra, HST, EVN, VLBA and the Liverpool Telescope. The averaged VHE gamma-ray spectrum can be fitted from 100GeV to 10TeV with a simple power law with a photon index of (-2.41 $\pm$ 0.07), while the integral flux above 300GeV is $(1.44 \pm 0.13) \times 10^{-12} cm^{-2} s^{-1}$. During the campaign between 2012 and 2015, M87 is generally found in a low emission state at all observed wavelengths. The VHE gamma-ray flux from the present 2012-2015 M87 campaign is consistent with a constant flux with some hint of variability ($\sim3\sigma$) on a daily timescale in 2013. The low-state gamma-ray emission likely originates from the same region as the flare-state emission. Given the broadband SED, both a leptonic synchrotron self Compton and a hybrid photo-hadronic model reproduce the available data well, even if the latter is preferred. We note, however, that the energy stored in the magnetic field in the leptonic scenario is very low suggesting a matter dominated emission region

The Great Markarian 421 Flare of 2010 February: Multiwavelength Variability and Correlation Studies

We report on variability and correlation studies using multiwavelength observations of the blazar Mrk 421 during the month of 2010 February, when an extraordinary flare reaching a level of ∼27 Crab Units above 1 TeV was measured in very high energy (VHE) γ-rays with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) observatory. This is the highest flux state for Mrk 421 ever observed in VHE γ-rays. Data are analyzed from a coordinated campaign across multiple instruments, including VHE γ-ray (VERITAS, Major Atmospheric Gamma-ray Imaging Cherenkov), high-energy γ-ray (Fermi-LAT), X-ray (Swift, Rossi X-ray Timing Experiment, MAXI), optical (including the GASP-WEBT collaboration and polarization data), and radio (Metsahovi, Owens Valley Radio Observatory, University of Michigan Radio Astronomy Observatory). Light curves are produced spanning multiple days before and after the peak of the VHE flare, including over several flare "decline" epochs. The main flare statistics allow 2 minute time bins to be constructed in both the VHE and optical bands enabling a cross-correlation analysis that shows evidence for an optical lag of ∼25-55 minutes, the first time-lagged correlation between these bands reported on such short timescales. Limits on the Doppler factor (δ ⪆ 33) and the size of the emission region (δ-1RB≲ 3.8 × 1013cm) are obtained from the fast variability observed by VERITAS during the main flare. Analysis of 10 minute binned VHE and X-ray data over the decline epochs shows an extraordinary range of behavior in the flux-flux relationship, from linear to quadratic to lack of correlation to anticorrelation. Taken together, these detailed observations of an unprecedented flare seen in Mrk 421 are difficult to explain with the classic single-zone synchrotron self-Compton model

Periastron Observations of TeV Gamma-Ray Emission from a Binary System with a 50-year Period

We report on observations of the pulsar / Be star binary system PSR J2032+4127 / MT91 213 in the energy range between 100 GeV and 20 TeV with the VERITAS and MAGIC imaging atmospheric Cherenkov telescope arrays. The binary orbit has a period of approximately 50 years, with the most recent periastron occurring on 2017 November 13. Our observations span from 18 months prior to periastron to one month after. A new, point-like, gamma-ray source is detected, coincident with the location of PSR J2032+4127 / MT91 213. The gamma-ray light curve and spectrum are well-characterized over the periastron passage. The flux is variable over at least an order of magnitude, peaking at periastron, thus providing a firm association of the TeV source with the pulsar / Be star system. Observations prior to periastron show a cutoff in the spectrum at an energy around 0.5 TeV. This result adds a new member to the small population of known TeV binaries, and it identifies only the second source of this class in which the nature and properties of the compact object are firmly established. We compare the gamma-ray results with the light curve measured with the X-ray Telescope (XRT) on board the Neil Gehrels Swift Observatory and with the predictions of recent theoretical models of the system. We conclude that significant revision of the models is required to explain the details of the emission we have observed, and we discuss the relationship between the binary system and the overlapping steady extended source, TeV J2032+4130

Carbon dioxide fluxes increase from day to night across European streams

Globally, inland waters emit over 2 Pg of carbon per year as carbon dioxide, of which the majority originates from streams and rivers. Despite the global significance of fluvial carbon dioxide emissions, little is known about their diel dynamics. Here we present a large-scale assessment of day- and night-time carbon dioxide fluxes at the water-air interface across 34 European streams. We directly measured fluxes four times between October 2016 and July 2017 using drifting chambers. Median fluxes are 1.4 and 2.1 mmol m−2 h−1 at midday and midnight, respectively, with night fluxes exceeding those during the day by 39%. We attribute diel carbon dioxide flux variability mainly to changes in the water partial pressure of carbon dioxide. However, no consistent drivers could be identified across sites. Our findings highlight widespread day-night changes in fluvial carbon dioxide fluxes and suggest that the time of day greatly influences measured carbon dioxide fluxes across European streams

MAGIC observations of the diffuse γ -ray emission in the vicinity of the Galactic center

Aims. In the presence of a sufficient amount of target material, γ-rays can be used as a tracer in the search for sources of Galactic cosmic rays (CRs). Here we present deep observations of the Galactic center (GC) region with the MAGIC telescopes and use them to infer the underlying CR distribution and to study the alleged PeV proton accelerator at the center of our Galaxy.Methods. We used data from ≈100 h observations of the GC region conducted with the MAGIC telescopes over five years (from 2012 to 2017). Those were collected at high zenith angles (58−70 deg), leading to a larger energy threshold, but also an increased effective collection area compared to low zenith observations. Using recently developed software tools, we derived the instrument response and background models required for extracting the diffuse emission in the region. We used existing measurements of the gas distribution in the GC region to derive the underlying distribution of CRs. We present a discussion of the associated biases and limitations of such an approach.Results. We obtain a significant detection for all four model components used to fit our data (Sgr A*, “Arc”, G0.9+0.1, and an extended component for the Galactic Ridge). We observe no significant difference between the γ-ray spectra of the immediate GC surroundings, which we model as a point source (Sgr A*) and the Galactic Ridge. The latter can be described as a power-law with index 2 and an exponential cut-off at around 20 TeV with the significance of the cut-off being only 2σ. The derived cosmic-ray profile hints to a peak at the GC position and with a measured profile index of 1.2 ± 0.3 is consistent with the 1/r radial distance scaling law, which supports the hypothesis of a CR accelerator at the GC. We argue that the measurements of this profile are presently limited by our knowledge of the gas distribution in the GC vicinity.</div

Broadband characterisation of the very intense TeV flares of the blazar 1ES 1959+650 in 2016

1ES 1959+650 is a bright TeV high-frequency-peaked BL Lac object exhibiting interesting features like "orphan" TeV flares and broad emission in the high-energy regime that are difficult to interpret using conventional one-zone Synchrotron Self-Compton (SSC) scenarios. We report the results from the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) observations in 2016 along with the multi-wavelength data from the Fermi Large Area Telescope (LAT) and Swift instruments. MAGIC observed 1ES 1959+650 with different emission levels in the very-high-energy (VHE, E> 100 GeV) gamma -ray band during 2016. In the long-term data, the X-ray spectrum becomes harder with increasing flux and a hint of a similar trend is also visible in the VHE band. An exceptionally high VHE flux reaching similar to 3 times the Crab Nebula flux was measured by MAGIC on the 13 and 14 of June, and 1 July 2016 (the highest flux observed since 2002). During these flares, the high-energy peak of the spectral energy distribution (SED) lies in the VHE domain and extends up to several TeV. The spectrum in the gamma -ray (both Fermi-LAT and VHE bands) and the X-ray bands are quite hard. On 13 June and 1 July 2016, the source showed rapid variations in the VHE flux within timescales of less than an hour. A simple one-zone SSC model can describe the data during the flares requiring moderate to large values of the Doppler factors (delta >= 30-60). Alternatively, the high-energy peak of the SED can be explained by a purely hadronic model attributed to proton-synchrotron radiation with jet power L-jet similar to 10(46) erg s(-1) and under high values of the magnetic field strength (similar to 100 G) and maximum proton energy (similar to few EeV). Mixed lepto-hadronic models require super-Eddington values of the jet power. We conclude that it is difficult to get detectable neutrino emission from the source during the extreme VHE flaring period of 2016

Monitoring of the radio galaxy M 87 during a low -emission state from m 2012 to 2015 with MAGIC

M 87 is one of the closest (z = 0.004 36) extragalactic sources emitting at very high energies (VHF, E > 100 GeV). The aim of this work is to locale the region of the VHF gamma-ray emission and to describe the observed broad-band spectral energy distribution (SED) during the low VHF gamma-ray state. The data from M 87 collected between 2012 and 2015 as part of a MAGIC monitoring programme are analysed and combined with multiwavelength data from Fermi-LAT, Chandra, HST, FVN, VLBA, and the Liverpool Telescope. The averaged VHE gamma-ray spectrum can be fitted from 100 GeV to 10 TeV with a simple power law with a photon index of (-2.41 0.07), while the integral flux above 300 GeV is (1.44 0.13) x 10-12 cm 2 s I. During the campaign between 2012 and 2015, M87 is generally found in a low-emission state at all observed wavelengths. The VIIE gamma-ray flux from the present 2012-2015M 87 campaign is consistent with a constant flux with some hint of variability ( 3 a) on a daily time-scale in 2013. The low-state gamma-ray emission likely originates from the same region as the flare-state emission. Given the broad-band SED, both a leptonic synchrotron self-Compton and a hybrid photohadronic model reproduce the available data well, even if the latter is preferred. We note, however, that the energy stored in the magnetic field in the leptonic scenario is very low, suggesting a matter-dominated emission region

Deep observations of the globular cluster M15 with the MAGIC telescopes

A population of globular clusters (GCs) has been recently established by the Fermi-LAT telescope as a new class of GeV γ-ray sources. Leptons accelerated to TeV energies, in the inner magnetospheres of MSPs or in their wind regions, should produce γ-rays through the inverse Compton scattering in the dense radiation field from the huge population of stars. We have conducted deep observations of the GC M15 with the MAGIC telescopes and used 165 h in order to search for γ-ray emission. A strong upper limit on the TeV γ-ray flux < 3.2× 10^{-13} cm^{-2 s^{-1}} above 300 GeV (< 0.26{{ per cent}} of the Crab nebula flux) has been obtained. We interpret this limit as a constraint on the efficiency of the acceleration of leptons in the magnetospheres of the MSPs. We constrain the injection rate of relativistic leptons, ηe, from the MSPs magnetospheres and their surrounding. We conclude that ηe must be lower than expected from the modelling of high-energy processes in MSP inner magnetospheres. For leptons accelerated with the power-law spectrum in the MSP wind regions, ηe is constrained to be much lower than derived for the wind regions around classical pulsars. These constraints are valid for the expected range of magnetic field strengths within the GC and for the range of likely energies of leptons injected from the inner magnetospheres, provided that the leptons are not removed from the GC very efficiently due to advection process. We discuss consequences of these constraints for the models of radiation processes around millisecond pulsars. </p