Immune sensing of nucleic acids in inflammatory skin diseases.

Endosomal and cytosolic nucleic acid receptors are important immune sensors required for the detection of infecting or replicating viruses. The intracellular location of these receptors allows viral recognition and, at the same time, avoids unnecessary immune activation to self-nucleic acids that are continuously released by dying host cells. Recent evidence, however, indicates that endogenous factors such as anti-microbial peptides have the ability to break this protective mechanism. Here, we discuss these factors and illustrate how they drive inflammatory responses by promoting immune recognition of self-nucleic acids in skin wounds and inflammatory skin diseases such as psoriasis and lupus

STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma

Development of a Li2MoO4 scintillating bolometer for low background physics

We present the performance of a 33 g Li2MoO4 crystal working as a scintillating bolometer. The crystal was tested for more than 400 h in a dilution refrigerator installed in the underground laboratory of Laboratori Nazionali del Gran Sasso (Italy). This compound shows promising features in the frame of neutron detection, dark matter search (solar axions) and neutrinoless double-beta decay physics. Low temperature scintillating properties were investigated by means of different alpha, beta/gamma and neutron sources, and for the first time the Light Yield for different types of interacting particle is estimated. The detector shows great ability of tagging fast neutron interactions and high intrinsic radiopurity levels (< 90 \muBq/kg for 238-U and < 110 \muBq/kg for 232-Th).Comment: revised versio

First bolometric measurement of the two neutrino double beta decay of 100^{100}Mo with a ZnMoO4_4 crystals array

The large statistics collected during the operation of a ZnMoO$_4$ array, for a total exposure of 1.3 kg $\cdot$ day of $^{100}$Mo, allowed the first bolometric observation of the two neutrino double beta decay of $^{100}$Mo. The observed spectrum of each crystal was reconstructed taking into account the different background contributions due to environmental radioactivity and internal contamination. The analysis of coincidences between the crystals allowed the assignment of constraints to the intensity of the different background sources, resulting in a reconstruction of the measured spectrum down to an energy of $\sim$300 keV. The half-life extracted from the data is T$_{1/2}^{2\nu}$= [7.15 $\pm$ 0.37 (stat) $\pm$ 0.66 (syst)] $\cdot$ 10$^{18}$ y.Comment: 6 pages, 2 figure, Accepted for publication in Journal of Physics G: Nuclear and Particle Physic

CUPID-0: the first array of enriched scintillating bolometers for 0decay investigations

The CUPID-0 detector hosted at the Laboratori Nazionali del Gran Sasso, Italy, is the first large array of enriched scintillating cryogenic detectors for the investigation of82Se neutrinoless double-beta decay (0). CUPID-0 aims at measuring a background index in the region of interest (RoI) for 0at the level of 10- 3 counts/(keV kg years), the lowest value ever measured using cryogenic detectors. CUPID-0 operates an array of Zn82Se scintillating bolometers coupled with bolometric light detectors, with a state of the art technology for background suppression and thorough protocols and procedures for the detector preparation and construction. In this paper, the different phases of the detector design and construction will be presented, from the material selection (for the absorber production) to the new and innovative detector structure. The successful construction of the detector lead to promising preliminary detector performance which is discussed here

First array of enriched Zn82^{82}Se bolometers to search for double beta decay

The R&D activity performed during the last years proved the potential of ZnSe scintillating bolometers to the search for neutrino-less double beta decay, motivating the realization of the first large-mass experiment based on this technology: CUPID-0. The isotopic enrichment in $^{82}$Se, the Zn$^{82}$Se crystals growth, as well as the light detectors production have been accomplished, and the experiment is now in construction at Laboratori Nazionali del Gran Sasso (Italy). In this paper we present the results obtained testing the first three Zn$^{82}$Se crystals operated as scintillating bolometers, and we prove that their performance in terms of energy resolution, background rejection capability and intrinsic radio-purity complies with the requirements of CUPID-0

Annihilation of low energy antiprotons in silicon

The goal of the AE$\mathrm{\bar{g}}$IS experiment at the Antiproton Decelerator (AD) at CERN, is to measure directly the Earth's gravitational acceleration on antimatter. To achieve this goal, the AE$\mathrm{\bar{g}}$IS collaboration will produce a pulsed, cold (100 mK) antihydrogen beam with a velocity of a few 100 m/s and measure the magnitude of the vertical deflection of the beam from a straight path. The final position of the falling antihydrogen will be detected by a position sensitive detector. This detector will consist of an active silicon part, where the annihilations take place, followed by an emulsion part. Together, they allow to achieve 1$$ precision on the measurement of $\bar{g}$ with about 600 reconstructed and time tagged annihilations. We present here, to the best of our knowledge, the first direct measurement of antiproton annihilation in a segmented silicon sensor, the first step towards designing a position sensitive silicon detector for the AE$\mathrm{\bar{g}}$IS experiment. We also present a first comparison with Monte Carlo simulations (GEANT4) for antiproton energies below 5 MeVComment: 21 pages in total, 29 figures, 3 table

Prospects for measuring the gravitational free-fall of antihydrogen with emulsion detectors

The main goal of the AEgIS experiment at CERN is to test the weak equivalence principle for antimatter. AEgIS will measure the free-fall of an antihydrogen beam traversing a moir\'e deflectometer. The goal is to determine the gravitational acceleration g for antihydrogen with an initial relative accuracy of 1% by using an emulsion detector combined with a silicon micro-strip detector to measure the time of flight. Nuclear emulsions can measure the annihilation vertex of antihydrogen atoms with a precision of about 1 - 2 microns r.m.s. We present here results for emulsion detectors operated in vacuum using low energy antiprotons from the CERN antiproton decelerator. We compare with Monte Carlo simulations, and discuss the impact on the AEgIS project.Comment: 20 pages, 16 figures, 3 table

Search for 14.4 keV solar axions from M1 transition of Fe-57 with CUORE crystals

We report the results of a search for axions from the 14.4 keV M1 transition from Fe-57 in the core of the sun using the axio-electric effect in TeO2 bolometers. The detectors are 5x5x5 cm3 crystals operated at about 10 mK in a facility used to test bolometers for the CUORE experiment at the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 43.65 kg d of data was made using a newly developed low energy trigger which was optimized to reduce the detectors energy threshold. An upper limit of 0.63 c kg-1 d-1 was established at 95% C.L.. From this value, a lower bound at 95% C.L. was placed on the Peccei-Quinn energy scale of fa >= 0.76 10**6 GeV for a value of S=0.55 for the flavor-singlet axial vector matrix element. Bounds are given for the interval 0.15 < S < 0.55.Comment: 14 pages, 6 figures, submitted to JCA

Double-beta decay of 130^{130}Te to the first 0+^{+} excited state of 130^{130}Xe with CUORICINO

The CUORICINO experiment was an array of 62 TeO$_{2}$ single-crystal bolometers with a total $^{130}$Te mass of $11.3\,$kg. The experiment finished in 2008 after more than 3 years of active operating time. Searches for both $0\nu$ and $2\nu$ double-beta decay to the first excited $0^{+}$ state in $^{130}$Xe were performed by studying different coincidence scenarios. The analysis was based on data representing a total exposure of N($^{130}$Te)$\cdot$t=$9.5\times10^{25}\,$y. No evidence for a signal was found. The resulting lower limits on the half lives are $T^{2\nu}_{1/2}(^{130} Te\rightarrow^{130} Xe^{*})>1.3\times10^{23}\,$y (90% C.L.), and $T^{0\nu}_{1/2}(^{130} Te\rightarrow^{130} Xe^{*})>9.4\times10^{23}\,$y (90% C.L.).Comment: 6 pages, 4 figure