Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to ...OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.
GVHD remains the major impediment to broader application of allogeneic haematopoietic SCT. It can be prevented completely, but at the expense of other complications, rejection, relapse or delayed ...immune reconstitution. No optimal prevention or treatment method has been defined. This is reflected by enormous heterogeneity in approaches in Europe. Retrospective comparisons between different policies, although warranted, do not give definite answers. In order to improve the present situation, an European Group for Blood and Marrow Transplantation and the European LeukemiaNet working group has developed in a Delphi-like approach recommendations for prophylaxis and treatment of GVHD in the most common allogeneic transplant setting, transplantation from an HLA-identical sibling or unrelated donor for standard risk malignant disease. The working group proposes these guidelines to be adopted as routine standard in transplantation centres and to be used as comparator in systematic studies evaluating the advantages and disadvantages of practices differing from these recommendations.
A neutrino with energy ∼290 TeV, IceCube-170922A, was detected in coincidence with the BL Lac object TXS 0506+056 during enhanced gamma-ray activity, with chance coincidence being rejected at ∼3 ...level. We monitored the object in the very-high-energy (VHE) band with the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes for ∼41 hr from 1.3 to 40.4 days after the neutrino detection. Day-timescale variability is clearly resolved. We interpret the quasi-simultaneous neutrino and broadband electromagnetic observations with a novel one-zone lepto-hadronic model, based on interactions of electrons and protons co-accelerated in the jet with external photons originating from a slow-moving plasma sheath surrounding the faster jet spine. We can reproduce the multiwavelength spectra of TXS 0506+056 with neutrino rate and energy compatible with IceCube-170922A, and with plausible values for the jet power of . The steep spectrum observed by MAGIC is concordant with internal γγ absorption above ∼100 GeV entailed by photohadronic production of a ∼290 TeV neutrino, corroborating a genuine connection between the multi-messenger signals. In contrast to previous predictions of predominantly hadronic emission from neutrino sources, the gamma-rays can be mostly ascribed to inverse Compton upscattering of external photons by accelerated electrons. The X-ray and VHE bands provide crucial constraints on the emission from both accelerated electrons and protons. We infer that the maximum energy of protons in the jet comoving frame can be in the range ∼1014 - 1018 eV.
The objective of this work is to evaluate the introduction of bonding technology in the assembly of beverage filling machines. In this specific field, bonding has two potential great advantages with ...respect to welding, that are the speed of application and the absence of thermal distortions. Furthermore, since it presents fewer risks for safety at work, it allows the simultaneous execution of other assembly operations. On the other hand, the use of bonding requires a design process integrated by tests related to the specific application and operating conditions, that in the case of food machinery are: i) bonding of low surface roughness, austenitic stainless steel without surface preparation but degreasing; ii) contact of the joint with the chemically aggressive substances used for cleaning and sanitization. In the present study, first a technical-economical comparison with welding (business case) was done on a component of the structure of a filling machine. Then the adhesive appropriate for the application was identified experimentally with tests on single-lap joints (SLJ) with different surface finishes and subjected to chemical aging under the cleaning and sanitization agents. Finally, the scale-up to a larger and more complex structure was performed by joining two modules of the outer casing of a filling machine.
Supermassive black holes with masses of millions to billions of solar masses are commonly found in the centers of galaxies. Astronomers seek to image jet formation using radio interferometry but ...still suffer from insufficient angular resolution. An alternative method to resolve small structures is to measure the time variability of their emission. Here we report on gamma-ray observations of the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes, revealing variability with doubling time scales faster than 4.8 min. Causality constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole. We suggest that the emission is associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the radio jet.
The current generation of ground-based imaging atmospheric Cherenkov telescopes (IACTs) operate in the very-high-energy (VHE) domain from ~100 GeV to ~100 TeV. They use electronic digital trigger ...systems to discern the Cherenkov light flashes emitted by extensive air showers (EASs), from the overwhelming light of the night sky (LoNS) background. Near the telescope energy threshold, the number of emitted Cherenkov photons by gamma-ray-induced EASs is comparable to the fluctuations of the LoNS and the photon distribution at the Cherenkov-imaging camera plane becomes patchy. This results in a severe loss of effectiveness of the digital triggers based on combinatorial logic of thresholded signals. A stereoscopic analog trigger system has been developed for improving the detection capabilities of the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes at the lowest energies. It is based on the analog sum of the photosensor electrical signals. In this article, the architectural design, technical performances, and configuration of this stereoscopic analog trigger, dubbed " Sum-Trigger-II ," are described.
Abstract
It is widely believed that the bulk of the Galactic cosmic rays is accelerated in supernova remnants (SNRs). However, no observational evidence of the presence of particles of PeV energies ...in SNRs has yet been found. The young historical SNR Cassiopeia A (Cas A) appears as one of the best candidates to study acceleration processes. Between 2014 December and 2016 October, we observed Cas A with the MAGIC telescopes, accumulating 158 h of good quality data. We derived the spectrum of the source from 100 GeV to 10 TeV. We also analysed ∼8 yr of Fermi-LAT to obtain the spectral shape between 60 MeV and 500 GeV. The spectra measured by the LAT and MAGIC telescopes are compatible within the errors and show a clear turn-off (4.6σ) at the highest energies, which can be described with an exponential cut-off at
$E_c = 3.5(^{+1.6}_{-1.0})_{{\rm stat}} (^{+0.8}_{-0.9})_{{\rm sys}}$
TeV. The gamma-ray emission from 60 MeV to 10 TeV can be attributed to a population of high-energy protons with a spectral index of ∼2.2 and an energy cut-off at ∼10 TeV. This result indicates that Cas A is not contributing to the high energy (∼PeV) cosmic ray sea in a significant manner at the present moment. A one-zone leptonic model fails to reproduce by itself the multiwavelength spectral energy distribution. Besides, if a non-negligible fraction of the flux seen by MAGIC is produced by leptons, the radiation should be emitted in a region with a low magnetic field (B⪅180 μG) like in the reverse shock.
Abstract
Extreme high-frequency-peaked BL Lac objects (EHBLs) are blazars that exhibit extremely energetic synchrotron emission. They also feature nonthermal gamma-ray emission whose peak lies in the ...very high-energy (VHE,
E
> 100 GeV) range, and in some sources exceeds 1 TeV: this is the case for hard-TeV EHBLs such as 1ES 0229+200. With the aim of increasing the EHBL population, 10 targets were observed with the MAGIC telescopes from 2010 to 2017, for a total of 265 hr of good-quality data. The data were complemented by coordinated
Swift
observations. The X-ray data analysis confirms that all but two sources are EHBLs. The sources show only a modest variability and a harder-when-brighter behavior, typical for this class of objects. At VHE gamma-rays, three new sources were detected and a hint of a signal was found for another new source. In each case, the intrinsic spectrum is compatible with the hypothesis of a hard-TeV nature of these EHBLs. The broadband spectral energy distributions (SEDs) of all sources are built and modeled in the framework of a single-zone, purely leptonic model. The VHE gamma-ray-detected sources were also interpreted with a spine–layer model and a proton synchrotron model. The three models provide a good description of the SEDs. However, the resulting parameters differ substantially in the three scenarios, in particular the magnetization parameter. This work presents the first mini catalog of VHE gamma-ray and multiwavelength observations of EHBLs.
Aims. We aim to characterize the multiwavelength emission from Markarian 501 (Mrk 501), quantify the energy-dependent variability, study the potential multiband correlations, and describe the ...temporal evolution of the broadband emission within leptonic theoretical scenarios. Methods. We organized a multiwavelength campaign to take place between March and July of 2012. Excellent temporal coverage was obtained with more than 25 instruments, including the MAGIC, FACT and VERITAS Cherenkov telescopes, the instruments on board the Swift and Fermi spacecraft, and the telescopes operated by the GASP-WEBT collaboration. Results. Mrk 501 showed a very high energy (VHE) gamma-ray flux above 0.2 TeV of ∼0.5 times the Crab Nebula flux (CU) for most of the campaign. The highest activity occurred on 2012 June 9, when the VHE flux was ∼3 CU, and the peak of the high-energy spectral component was found to be at ∼2 TeV. Both the X-ray and VHE gamma-ray spectral slopes were measured to be extremely hard, with spectral indices < 2 during most of the observing campaign, regardless of the X-ray and VHE flux. This study reports the hardest Mrk 501 VHE spectra measured to date. The fractional variability was found to increase with energy, with the highest variability occurring at VHE. Using the complete data set, we found correlation between the X-ray and VHE bands; however, if the June 9 flare is excluded, the correlation disappears (significance < 3σ) despite the existence of substantial variability in the X-ray and VHE bands throughout the campaign. Conclusions. The unprecedentedly hard X-ray and VHE spectra measured imply that their low- and high-energy components peaked above 5 keV and 0.5 TeV, respectively, during a large fraction of the observing campaign, and hence that Mrk 501 behaved like an extreme high-frequency-peaked blazar (EHBL) throughout the 2012 observing season. This suggests that being an EHBL may not be a permanent characteristic of a blazar, but rather a state which may change over time. The data set acquired shows that the broadband spectral energy distribution (SED) of Mrk 501, and its transient evolution, is very complex, requiring, within the framework of synchrotron self-Compton (SSC) models, various emission regions for a satisfactory description. Nevertheless the one-zone SSC scenario can successfully describe the segments of the SED where most energy is emitted, with a significant correlation between the electron energy density and the VHE gamma-ray activity, suggesting that most of the variability may be explained by the injection of high-energy electrons. The one-zone SSC scenario used reproduces the behavior seen between the measured X-ray and VHE gamma-ray fluxes, and predicts that the correlation becomes stronger with increasing energy of the X-rays.
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 2
σ
. 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.