The Neuropeptide Alpha-Melanocyte-Stimulating Hormone Is Critically Involved in the Development of Cytotoxic CD8+ T Cells in Mice and Humans

BACKGROUND: The neuropeptide alpha-melanocyte-stimulating hormone is well known as a mediator of skin pigmentation. More recently, it has been shown that alpha-melanocyte-stimulating hormone also plays pivotal roles in energy homeostasis, sexual function, and inflammation or immunomodulation. Alpha-melanocyte-stimulating hormone exerts its antiinflammatory and immunomodulatory effects by binding to the melanocortin-1 receptor, and since T cells are important effectors during immune responses, we investigated the effects of alpha-melanocyte-stimulating hormone on T cell function. METHODOLOGY/PRINCIPAL FINDINGS: T cells were treated with alpha-melanocyte-stimulating hormone, and subsequently, their phenotype and function was analyzed in a contact allergy as well as a melanoma model. Furthermore, the relevance of alpha-melanocyte-stimulating hormone-mediated signaling for the induction of cytotoxicity was assessed in CD8(+) T cells from melanoma patients with functional and nonfunctional melanocortin-1 receptors. Here we demonstrate that the melanocortin-1 receptor is expressed by murine as well as human CD8(+) T cells, and we furthermore show that alpha-melanocyte-stimulating hormone/melanocortin-1 receptor-mediated signaling is critical for the induction of cytotoxicity in human and murine CD8(+) T cells. Upon adoptive transfer, alpha-melanocyte-stimulating hormone-treated murine CD8(+) T cells significantly reduced contact allergy responses in recipient mice. Additionally, the presented data indicate that alpha-melanocyte-stimulating hormone via signaling through a functional melanocortin-1 receptor augmented antitumoral immunity by up-regulating the expression of cytotoxic genes and enhancing the cytolytic activity in tumor-specific CD8(+) T cells. CONCLUSIONS/SIGNIFICANCE: Together, these results point to an important role of alpha-melanocyte-stimulating hormone in MHC class I-restricted cytotoxicity. Therefore, treatment of contact allergies or skin cancer with alpha-melanocyte-stimulating hormone or other more stable agonists of melanocortin-1 receptor might ameliorate disease or improve antitumoral immune responses

The accretion mechanism in low-power radio galaxies

We study a sample of 44 low-luminosity radio-loud AGN, which represent a range of nuclear radio-power spanning 5 orders of magnitude, to unveil the accretion mechanism in these galaxies. We estimate the accretion rate of gas associated with their hot coronae by analyzing archival Chandra data, to derive the deprojected density and temperature profiles in a spherical approximation. Measuring the jet power from the nuclear radio-luminosity, we find that the accretion power correlates linearly with the jet power, with an efficiency of conversion from rest mass into jet power of ~0.012. These results strengthen and extend the validity of the results obtained by Allen and collaborators for 9 radio galaxies, indicating that hot gas accretion is the dominant process in FR I radio galaxies across their full range of radio-luminosity. We find that the different levels of nuclear activity are driven by global differences in the structure of the galactic hot coronae. A linear relation links the jet power with the host X-ray surface brightness. This implies that a substantial change in the jet power must be accompanied by a global change in its ISM properties, driven for example by a major merger. This correlation provides a simple widely applicable method to estimate the jet-power of a given object by observing the intensity of its host X-ray emission. To maintain the mass flow in the jet, the fraction of gas that crosses the Bondi radius reaching the accretion disk must be > 0.002. This implies that the radiative efficiency of the disk must be < 0.005, an indication that accretion in these objects occurs not only at a lower rate, but also at lower efficiency than in standard accretion disks.Comment: Accepted for publication in A&

Lumen-apposing metal stent through the meshes of duodenal metal stents for palliation of malignant jaundice

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard procedure for malignant jaundice palliation; however, it can be challenging when a duodenal self-expandable metal stent (SEMS) is already in place. Patients and methods The primary aim of our study was to evaluate the technical feasibility of the placement of a lumen apposing metal stent (LAMS) through the mesh (TTM) of duodenal stents. The secondary aims were to evaluate clinical outcomes and adverse events (AEs) related to the procedures. Results Data from 23 patients (11 F and 12 M; mean age: 69.5 ± 11 years old) were collected. In 17 patients (73.9 %) TTM LAMS placement was performed as first intention, while in six patients (26.1 %) it was performed after a failed ERCP. Thirteen patients (56.5 %) underwent the procedure due to advanced pancreatic head neoplasia. One technical failure was experienced (4.3 %). The TTM LAMS placement led to a significant decrease in the serum levels of bilirubin, ALP, GGT, WBC and CRP. No cases of duodenal SEMS occlusion occurred and no other AEs were observed during the follow-up. Conclusions Concomitant malignant duodenal and biliary obstruction is a challenging condition. Palliation of jaundice using TTM LAMS in patients already treated with duodenal stent is associated to promising technical and clinical outcomes

Radio Sources in Low-Luminosity Active Galactic Nuclei. III. "AGNs" in a Distance-Limited Sample of "LLAGNs"

(abbreviated): This paper presents the results of a high resolution radio imaging survey of all known (96) low-luminosity active galactic nuclei (LLAGNs) at D<19Mpc. We find that almost half of all LINERs and low-luminosity Seyferts have flat-spectrum radio cores when observed at 150mas resolution. Higher (2mas) resolution observations of a flux-limited subsample have provided a 100% (16 of 16) detection rate of pc-scale radio cores, with implied brightness temperatures > 10^8 K. The five LLAGNs with the highest core radio fluxes also have pc-scale `jets.' Compact radio cores are almost exclusively found in massive ellipticals and in type1 nuclei. The core radio power is correlated with the nuclear optical `broad' Halpha luminosity, the nuclear optical `narrow' emission line luminosity and width, and with the galaxy luminosity. In these correlations LLAGNs fall close to the low-luminosity extrapolations of more powerful AGNs. About half of all LLAGNs with multiple epoch data show significant inter-year radio variability. Investigation of a sample of ~150 nearby bright galaxies, most of them LLAGNs, shows that the nuclear (<150mas size) radio power is strongly correlated with both the black hole mass and the galaxy bulge luminosity; linear regression fits to all ~150 galaxies give: log P(2cm) = 1.31 log M_blackhole + 8.77 and log P(2cm) = 1.89 log L_B(bulge) - 0.17. Low accretion rates are implied in both advection- and jet-type models. In brief, all evidence points towards the presence of accreting massive black holes in a large fraction, perhaps all, of LLAGNs.Comment: to appear in A&

Radio galaxies in the 2SLAQ Luminous Red Galaxy survey: II. The stellar populations of radio-loud and radio-quiet LRGs

We present an analysis of the optical spectra of a volume-limited sample of 375 radio galaxies at redshift 0.4<z<0.7 from the 2dF-SDSS Luminous Red Galaxy and QSO (2SLAQ) redshift survey. We investigate the evolution of the stellar populations and emission-line properties of these galaxies. By constructing composite spectra and comparing with a matched sample of radio-quiet sources from the same survey, we also investigate the effect on the galaxy of the presence of an active nucleus. The composite spectra, binned by redshift and radio luminosity, all require two components to describe them, which we interpret as an old and a younger population. We found no evolution with redshift of the age of the younger population in radio galaxies, nor were they different from the radio-quiet comparison sample. Similarly, there is no correlation with radio power, with the exception that the most powerful radio sources (P(1.4) > 10^26 W/Hz) have younger stars and stronger emission lines than the less powerful sources. This suggests that we have located the threshold in radio power where strong emission lines "switch on", at radio powers of around 10^26 W/Hz. Except for the very powerful radio galaxies, the presence of a currently-active radio AGN does not appear to be correlated with any change in the observed stellar population of a luminous red galaxy at z~0.5.Comment: 10 pages, 10 figures and 2 tables, accepted for publication in MNRA

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Effect of the relative shift between the electron density and temperature pedestal position on the pedestal stability in JET-ILW and comparison with JET-C

The electron temperature and density pedestals tend to vary in their relative radial positions, as observed in DIII-D (Beurskens et al 2011 Phys. Plasmas 18 056120) and ASDEX Upgrade (Dunne et al 2017 Plasma Phys. Control. Fusion 59 14017). This so-called relative shift has an impact on the pedestal magnetohydrodynamic (MHD) stability and hence on the pedestal height (Osborne et al 2015 Nucl. Fusion 55 063018). The present work studies the effect of the relative shift on pedestal stability of JET ITER-like wall (JET-ILW) baseline low triangularity (\u3b4) unseeded plasmas, and similar JET-C discharges. As shown in this paper, the increase of the pedestal relative shift is correlated with the reduction of the normalized pressure gradient, therefore playing a strong role in pedestal stability. Furthermore, JET-ILW tends to have a larger relative shift compared to JET carbon wall (JET-C), suggesting a possible role of the plasma facing materials in affecting the density profile location. Experimental results are then compared with stability analysis performed in terms of the peeling-ballooning model and with pedestal predictive model EUROPED (Saarelma et al 2017 Plasma Phys. Control. Fusion). Stability analysis is consistent with the experimental findings, showing an improvement of the pedestal stability, when the relative shift is reduced. This has been ascribed mainly to the increase of the edge bootstrap current, and to minor effects related to the increase of the pedestal pressure gradient and narrowing of the pedestal pressure width. Pedestal predictive model EUROPED shows a qualitative agreement with experiment, especially for low values of the relative shift

A study of CP violation in B-+/- -&gt; DK +/- and B-+/- -&gt; D pi(+/-) decays with D -&gt; (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes

Measurement of Upsilon production in collisions at root s=2.76 TeV

The production of $\Upsilon(1S)$, $\Upsilon(2S)$ and $\Upsilon(3S)$ mesons decaying into the dimuon final state is studied with the LHCb detector using a data sample corresponding to an integrated luminosity of 3.3 $pb^{-1}$ collected in proton-proton collisions at a centre-of-mass energy of $\sqrt{s}=2.76$ TeV. The differential production cross-sections times dimuon branching fractions are measured as functions of the $\Upsilon$ transverse momentum and rapidity, over the ranges $p_{\rm T} Upsilon(1S) X) x B(Upsilon(1S) -> mu+mu-) = 1.111 +/- 0.043 +/- 0.044 nb, sigma(pp -> Upsilon(2S) X) x B(Upsilon(2S) -> mu+mu-) = 0.264 +/- 0.023 +/- 0.011 nb, sigma(pp -> Upsilon(3S) X) x B(Upsilon(3S) -> mu+mu-) = 0.159 +/- 0.020 +/- 0.007 nb, where the first uncertainty is statistical and the second systematic