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.
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.
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.
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.
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.
We report the detection of pulsed gamma-ray emission from the Geminga pulsar (PSR J0633+1746) between 15 GeV and 75 GeV. This is the first time a middle-aged pulsar has been detected up to these ...energies. Observations were carried out with the MAGIC telescopes between 2017 and 2019 using the low-energy threshold Sum-Trigger-II system. After quality selection cuts, ∼80 h of observational data were used for this analysis. To compare with the emission at lower energies below the sensitivity range of MAGIC, 11 years of
Fermi
-LAT data above 100 MeV were also analysed. From the two pulses per rotation seen by
Fermi
-LAT, only the second one,
P
2, is detected in the MAGIC energy range, with a significance of 6.3
σ
. The spectrum measured by MAGIC is well-represented by a simple power law of spectral index Γ = 5.62 ± 0.54, which smoothly extends the
Fermi
-LAT spectrum. A joint fit to MAGIC and
Fermi
-LAT data rules out the existence of a sub-exponential cut-off in the combined energy range at the 3.6
σ
significance level. The power-law tail emission detected by MAGIC is interpreted as the transition from curvature radiation to Inverse Compton Scattering of particles accelerated in the northern outer gap.
The immunosuppressive properties of mesenchymal stem cells (MSC) make them particularly attractive to manipulate graft-versus-host disease (GVHD). So far, the experience of using MSC to treat GVHD is ...limited to a few cases, controversial results come from preclinical models and several issues remain to be clarified. The present studies were designed to address these questions in a xenogenic model testing the ability of umbilical cord blood-derived MSC (UCB-MSC) to prevent and/or treat GVHD. Sublethally irradiatiated non-obese diabetic/severe combined immunodeficiency NOD/SCID mice transplanted with human peripheral blood mononuclear cells (huPBMC) showed extensive human T-cell proliferation in the peripheral blood, lymphoid and non-lymphoid tissues, which evolved in extensive GVHD (wasting, ruffled hair and hunched back). The mice treated with a single dose of UCB-MSC did not behave differently form the controls. However, when UCB-MSC were given at weekly intervals, there was a marked decrease in human T-cell proliferation and none of the mice developed GVHD. No therapeutic effect was obtained if UCB-MSC were administered at onset of GVHD. This work supports the clinical use of MSC in stem cell transplantation as a prophylaxis rather than treatment of GVHD.
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