Optimized "in vitro" culture conditions for human rheumatoid arthritis synovial fibroblasts

The composition of synovial fluid in rheumatoid arthritis (RA) is complex and strongly influences the microenvironment of joints and it is an inseparable element of the disease. Currently, \u201cin vitro\u201d studies are performed on RA cells cultured in the presence of either recombinant proinflammatory cytokines-conditioned medium or medium alone. In this study, we evaluated the use of synovial fluid, derived from RA patients, as optimal culture condition to perform \u201cin vitro\u201d studies on RA synovial fibroblasts. We observed that synovial fluid is more effective in inducing cell proliferation with respect to TNF-alpha or culture medium alone. Spontaneous apoptosis in fibroblasts was also decreased in response to synovial fluid. The expression of proinflammatory cytokines in the presence of synovial fluid was significantly elevated with respect to cells cultured with TNF-alpha or medium, and the overall morphology of cells was also modified. In addition, modulation of intracellular calcium dynamics elicited in response to synovial fluid or TNF-alpha exposure is different and suggests a role for the purinergic signalling in the modulation of the effects. These results emphasize the importance of using RA synovial fluid in \u201cin vitro\u201d studies involving RA cells, in order to reproduce faithfully the physiopathological environmental characteristic of RA joints

A invenção como ofício: as máquinas de preparo e benefício do café no século XIX

The article studies the Brazilian coffee-growing society from the point of view of the generation of inventions and machine innovations aimed at the preparation and processing of coffee beans in the period between 1860 and 1882. Under the protection of the 1830 Patents Law, the machinistas developed their inventions and submitted them to the National Industry Auxiliary Society (Sociedade Auxiliadora da Indústria Nacional - SAIN) for the concession of industrial privilege and later manufacture and commercialization. It is demonstrated how the coffee machinery developed by these inventors-entrepreneurs in Brazil brought to the slave-labour coffee plantation the technological update of agricultural machines existing in the industrial countries and how that has propitiated an improvement in the quality of large-scale coffee bean processing. This fact has made possible not only the consolidation of the country as the largest exporter in the international market, but has also has allowed for changes in the productive structure of the slave-labour plantations.Aborda-se a sociedade cafeeira brasileira sob o aspecto da geração de invenções e inovações de máquinas destinadas ao preparo e benefício do café no período de 1860 a 1882. Sob a proteção da Lei de Patentes de 1830, os machinistas desenvolviam seus inventos, que eram examinados pela Sociedade Auxiliadora da Indústria Nacional (SAIN) para concessão do privilégio industrial e posterior fabricação e comercialização. Demonstra-se como as máquinas de café desenvolvidas por estes inventores-empresários no Brasil trouxeram para a fazenda cafeeira escravista a atualização tecnológica de máquinas agrícolas existentes nos países industriais e propiciaram uma melhoria de qualidade do benefício em grandes quantidades de café. Tal fato tornou possível não só a consolidação do país como maior exportador no mercado internacional, mas permitiu alterações na estrutura produtiva das fazendas escravistas

An integrated study of the chemical composition of Antarctic aerosol to investigate natural and anthropogenic sources

During the 2010-11 austral summer, an aerosol sampling campaign was carried out at a coastal Antarctic site (Terra Nova Bay, Victoria Land). In this work, previously published data about water-soluble organic compounds and major and trace elements were merged with novel measurements of major ions, carboxylic acids and persistent organic pollutants (polychlorobiphenyls, polycyclic aromatic hydrocarbons, polychlorinated naphthalenes, polybrominated diphenylethers and organochlorine pesticides) in order to provide a chemical characterisation of Antarctic aerosol and to investigate its sources. The persistent organic pollutants were determined using a high-volume sampler, able to collect both particulate and gaseous fractions, whereas remaining compounds were determined by performing an aerosol size fractionation with a PM10 cascade impactor. Ionic species represented 58% (350 ng m(-3)) of the sum of concentrations of all detected compounds (596 ng m(-3)) in our Antarctic PM10 aerosol samples due to natural emission. Trace concentrations of persistent organic pollutants highlighted that the occurrence of these species can be due to long-range atmospheric transport or due to the research base. Factor analysis was applied to the dataset obtained from the samples collected with the PM10 sampler in order to make a distinction between anthropogenic, crustal and biogenic sources using specific chemical markers

Follow-up observations of GW170817 with the MAGIC telescopes

The discovery of the electromagnetic counterpart AT2017gfo and the GRB 170817A, associated to the binary neutron star merger GW170817, was one of the major advances in the study of gamma-ray bursts (GRBs) and the hallmark of the multi-messenger astronomy with gravitational waves. Another breakthrough in GRB physics is represented by the discovery of the highly energetic, teraelectronvolt (TeV) component in the GRB 190114C, possibly an universal component in all GRBs. This conclusion is also suggested by the hint of TeV emission in the short GRB 160821B and a few more events reported in the literature. The missing observational piece is the joint detection of TeV emission and gravitational waves from a short GRB and its progenitor. MAGIC observed the counterpart AT2017gfo as soon as the visibility conditions allowed it, namely from January to June 2018. These observations correspond to the maximum flux level observed in the radio and X-ray bands. The upper limits derived from TeV observations are compared with the modelling of the late non-thermal emission using the multi-frequency SED

Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation

The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for $\gamma$-ray astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of $\gamma$-ray cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of $\gamma$-ray absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift $z=2$ and to constrain or detect $\gamma$-ray halos up to intergalactic-magnetic-field strengths of at least 0.3pG. Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from $\gamma$-ray astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of $\gamma$-ray cosmology

Sensitivity of the Cherenkov Telescope Array to a dark matter signal from the Galactic centre

We provide an updated assessment of the power of the Cherenkov Telescope Array (CTA) to search for thermally produced dark matter at the TeV scale, via the associated gamma-ray signal from pair-annihilating dark matter particles in the region around the Galactic centre. We find that CTA will open a new window of discovery potential, significantly extending the range of robustly testable models given a standard cuspy profile of the dark matter density distribution. Importantly, even for a cored profile, the projected sensitivity of CTA will be sufficient to probe various well-motivated models of thermally produced dark matter at the TeV scale. This is due to CTA's unprecedented sensitivity, angular and energy resolutions, and the planned observational strategy. The survey of the inner Galaxy will cover a much larger region than corresponding previous observational campaigns with imaging atmospheric Cherenkov telescopes. CTA will map with unprecedented precision the large-scale diffuse emission in high-energy gamma rays, constituting a background for dark matter searches for which we adopt state-of-the-art models based on current data. Throughout our analysis, we use up-to-date event reconstruction Monte Carlo tools developed by the CTA consortium, and pay special attention to quantifying the level of instrumental systematic uncertainties, as well as background template systematic errors, required to probe thermally produced dark matter at these energies.</p

Multiwavelength study of the galactic PeVatron candidate LHAASO J2108+5157

Context. Several new ultrahigh-energy (UHE) γ-ray sources have recently been discovered by the Large High Altitude Air Shower Observatory (LHAASO) collaboration. These represent a step forward in the search for the so-called Galactic PeVatrons, the enigmatic sources of the Galactic cosmic rays up to PeV energies. However, it has been shown that multi-TeV γ-ray emission does not necessarily prove the existence of a hadronic accelerator in the source; indeed this emission could also be explained as inverse Compton scattering from electrons in a radiation-dominated environment. A clear distinction between the two major emission mechanisms would only be made possible by taking into account multi-wavelength data and detailed morphology of the source. Aims. We aim to understand the nature of the unidentified source LHAASO J2108+5157, which is one of the few known UHE sources with no very high-energy (VHE) counterpart. Methods. We observed LHAASO J2108+5157 in the X-ray band with XMM-Newton in 2021 for a total of 3.8 hours and at TeV energies with the Large-Sized Telescope prototype (LST-1), yielding 49 hours of good-quality data. In addition, we analyzed 12 years of Fermi-LAT data, to better constrain emission of its high-energy (HE) counterpart 4FGL J2108.0+5155. We used naima and jetset software packages to examine the leptonic and hadronic scenario of the multi-wavelength emission of the source. Results. We found an excess (3.7σ) in the LST-1 data at energies E &gt; 3 TeV. Further analysis of the whole LST-1 energy range, assuming a point-like source, resulted in a hint (2.2σ) of hard emission, which can be described with a single power law with a photon index of Σ = 1.6 ± 0.2 the range of 0.3 - 100 TeV. We did not find any significant extended emission that could be related to a supernova remnant (SNR) or pulsar wind nebula (PWN) in the XMM-Newton data, which puts strong constraints on possible synchrotron emission of relativistic electrons. We revealed a new potential hard source in Fermi-LAT data with a significance of 4σ and a photon index of Σ = 1.9 ± 0.2, which is not spatially correlated with LHAASO J2108+5157, but including it in the source model we were able to improve spectral representation of the HE counterpart 4FGL J2108.0+5155. Conclusions. The LST-1 and LHAASO observations can be explained as inverse Compton-dominated leptonic emission of relativistic electrons with a cutoff energy of 100-30+70 TeV. The low magnetic field in the source imposed by the X-ray upper limits on synchrotron emission is compatible with a hypothesis of a PWN or a TeV halo. Furthermore, the spectral properties of the HE counterpart are consistent with a Geminga-like pulsar, which would be able to power the VHE-UHE emission. Nevertheless, the lack of a pulsar in the neighborhood of the UHE source is a challenge to the PWN/TeV-halo scenario. The UHE γ rays can also be explained as π0 decay-dominated hadronic emission due to interaction of relativistic protons with one of the two known molecular clouds in the direction of the source. Indeed, the hard spectrum in the LST-1 band is compatible with protons escaping a shock around a middle-aged SNR because of their high low-energy cut-off, but the origin of the HE γ-ray emission remains an open question

Observations of the Crab Nebula and Pulsar with the Large-sized Telescope Prototype of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is a next-generation ground-based observatory for gamma-ray astronomy at very high energies. The Large-Sized Telescope prototype (LST-1) is located at the CTA-North site, on the Canary Island of La Palma. LSTs are designed to provide optimal performance in the lowest part of the energy range covered by CTA, down to ≃20 GeV. LST-1 started performing astronomical observations in 2019 November, during its commissioning phase, and it has been taking data ever since. We present the first LST-1 observations of the Crab Nebula, the standard candle of very-high-energy gamma-ray astronomy, and use them, together with simulations, to assess the performance of the telescope. LST-1 has reached the expected performance during its commissioning period—only a minor adjustment of the preexisting simulations was needed to match the telescope’s behavior. The energy threshold at trigger level is around 20 GeV, rising to ≃30 GeV after data analysis. Performance parameters depend strongly on energy, and on the strength of the gamma-ray selection cuts in the analysis: angular resolution ranges from 0.°12-0.°40, and energy resolution from 15%-50%. Flux sensitivity is around 1.1% of the Crab Nebula flux above 250 GeV for a 50 hr observation (12% for 30 minutes). The spectral energy distribution (in the 0.03-30 TeV range) and the light curve obtained for the Crab Nebula agree with previous measurements, considering statistical and systematic uncertainties. A clear periodic signal is also detected from the pulsar at the center of the Nebula

Multi-year characterisation of the broad-band emission from the intermittent extreme BL Lac 1ES 2344+514

Aims. The BL Lac 1ES 2344+514 is known for temporary extreme properties characterised by a shift of the synchrotron spectral energy distribution (SED) peak energy νsynch;p above 1 keV. While those extreme states have only been observed during high flux levels thus far, additional multi-year observing campaigns are required to achieve a coherent picture. Here, we report the longest investigation of the source from radio to very high energy (VHE) performed so far, focussing on a systematic characterisation of the intermittent extreme states. Methods.We organised a monitoring campaign covering a 3-year period from 2019 to 2021.Morethan ten instruments participated in the observations in order to cover the emission from radio to VHE. In particular, sensitive X-ray measurements by XMM-Newton, NuSTAR, and AstroSat took place simultaneously with multi-hour MAGIC observations, providing an unprecedented constraint of the two SED components for this blazar. Results. While our results confirm that 1ES 2344+514 typically exhibits νsynch;p > 1 keV during elevated flux periods, we also find periods where the extreme state coincides with low flux activity. A strong spectral variability thus happens in the quiescent state, and is likely caused by an increase in the electron acceleration efficiency without a change in the electron injection luminosity. On the other hand, we also report a strong X-ray flare (among the brightest for 1ES 2344+514) without a significant shift of νsynch;p. During this particular flare, the X-ray spectrum is among the softest of the campaign. It unveils complexity in the spectral evolution, where the common harder-when-brighter trend observed in BL Lacs is violated. By combining Swift-XRT and Swift-UVOT measurements during a low and hard X-ray state, we find an excess of the UV flux with respect to an extrapolation of the X-ray spectrum to lower energies. This UV excess implies that at least two regions significantly contribute to the infrared/optical/ultraviolet/X-ray emission. Using the simultaneous MAGIC, XMM-Newton, NuSTAR, and AstroSat observations, we argue that a region possibly associated with the 10 GHz radio core may explain such an excess. Finally, we investigate a VHE flare, showing an absence of simultaneous variability in the 0.3-2 keV band. Using time-dependent leptonic modelling, we show that this behaviour, in contradiction to single-zone scenarios, can instead be explained by a two-component model