Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response

Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis

The Aguablanca Ni–(Cu) sulfide deposit, SW Spain: geologic and geochemical controls and the relationship with a midcrustal layered mafic complex

The Aguablanca Ni–(Cu) sulfide deposit is hosted by a breccia pipe within a gabbro–diorite pluton. The deposit probably formed due to the disruption of a partially crystallized layered mafic complex at about 12– 19 km depth and the subsequent emplacement of melts and breccias at shallow levels (<2 km). The ore-hosting breccias are interpreted as fragments of an ultramafic cumulate, which were transported to the near surface along with a molten sulfide melt. Phlogopite Ar–Ar ages are 341– 332 Ma in the breccia pipe, and 338–334 Ma in the layered mafic complex, and are similar to recently reported U–Pb ages of the host Aguablanca Stock and other nearby calcalkaline metaluminous intrusions (ca. 350–330 Ma). Ore deposition resulted from the combination of two critical factors, the emplacement of a layered mafic complex deep in the continental crust and the development of small dilational structures along transcrustal strike-slip faults that triggered the forceful intrusion of magmas to shallow levels. The emplacement of basaltic magmas in the lower middle crust was accompanied by major interaction with the host rocks, immiscibility of a sulfide melt, and the formation of a magma chamber with ultramafic cumulates and sulfide melt at the bottom and a vertically zoned mafic to intermediate magmas above. Dismembered bodies of mafic/ultramafic rocks thought to be parts of the complex crop out about 50 km southwest of the deposit in a tectonically uplifted block (Cortegana Igneous Complex, Aracena Massif). Reactivation of Variscan structures that merged at the depth of the mafic complex led to sequential extraction of melts, cumulates, and sulfide magma. Lithogeochemistry and Sr and Nd isotope data of the Aguablanca Stock reflect the mixing from two distinct reservoirs, i.e., an evolved siliciclastic middle-upper continental crust and a primitive tholeiitic melt. Crustal contamination in the deep magma chamber was so intense that orthopyroxene replaced olivine as the main mineral phase controlling the early fractional crystallization of the melt. Geochemical evidence includes enrichment in SiO2 and incompatible elements, and Sr and Nd isotope compositions (87Sr/86Sri 0.708–0.710; 143Nd/144Ndi 0.512–0.513). However, rocks of the Cortegana Igneous Complex have low initial 87Sr/86Sr and high initial 143Nd/144Nd values suggesting contamination by lower crustal rocks. Comparison of the geochemical and geological features of igneous rocks in the Aguablanca deposit and the Cortegana Igneous Complex indicates that, although probably part of the same magmatic system, they are rather different and the rocks of the Cortegana Igneous Complex were not the direct source of the Aguablanca deposit. Crust–magma interaction was a complex process, and the generation of orebodies was controlled by local but highly variable factors. The model for the formation of the Aguablanca deposit presented in this study implies that dense sulfide melts can effectively travel long distances through the continental crust and that dilational zones within compressional belts can effectively focus such melt transport into shallow environments

Downscaling Climate Change Impacts, Socio-Economic Implications and Alternative Adaptation Pathways for Islands and Outermost Regions

This book provides a comprehensive overview of the future scenarios of climate change and management concerns associated with climate change impacts on the blue economy of European islands and outermost regions. The publication collects major findings of the SOCLIMPACT project’s research outcomes, aiming to raise social awareness among policy-makers and industry about climate change consequences at local level, and provide knowledge-based information to support policy design, from local to national level. This comprehensive book will also assist students, scholars and practitioners to understand, conceptualize and effectively and responsibly manage climate change information and applied research. This book provides invaluable material for Blue Growth Management, theory and application, at all levels. This first edition includes up-to-date data, statistics, references, case material and figures of the 12 islands case studies. ¨Downscaling climate change impacts, socio-economic implications and alternative adaptation pathways for Islands and Outermost Regions¨ is a must-read book, given the accessible style and breadth and depth with which the topic is dealt. The book is an up-to-date synthesis of key knowledge on this area, written by a multidisciplinary group of experts on climate and economic modelling, and policy design

80Se(n,?) cross-section measurement at CERN n TOF

Radiative neutron capture cross section measurements are of fundamental importance for the study of the slow neutron capture (s-) process of nucleosynthesis. This mechanism is responsible for the formation of most elements heavier than iron in the Universe. Particularly relevant are branching nuclei along the s-process path, which are sensitive to the physical conditions of the stellar environment. One such example is the branching at $^{79}$Se (3.27 × 10$^{5}$ y), which shows a thermally dependent β-decay rate. However, an astrophysically consistent interpretation requires also the knowledge of the closest neighbour isotopes involved. In particular, the $^{80}$Se(n,γ) cross section directly affects the stellar yield of the "cold" branch leading to the formation of the s-only $^{82}$Kr. Experimentally, there exists only one previous measurement on $^{80}$Se using the time of flight (TOF) technique. However, the latter suffers from some limitations that are described in this presentation. These drawbacks have been significantly improved in a recent measurement at CERN n TOF. This contribution presents a summary of the latter measurement and the status of the data analysis

First results of the Am-241(n,f) cross section measurement at the Experimental Area 2 of the n_TOF facility at CERN

This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme Human Resources Development, Education and Lifelong Learning in the context of the project "Strengthening Human Resources Research Potential via Doctorate Research" (MIS-5000432), implemented by the State Scholarships Foundation (IKY). Also, the authors would like to acknowledge the support of the European Commission under the CHANDA project (7th Framework Programme).Feasibility, design and sensitivity studies on innovative nuclear reactors that could address the issue of nuclear waste transmutation using fuels enriched in minor actinides, require high accuracy cross section data for a variety of neutron-induced reactions from thermal energies to several tens of MeV. The isotope Am-241 (T-1/2= 433 years) is present in high-level nuclear waste (HLW), representing about 1.8 % of the actinide mass in spent PWR UOx fuel. Its importance increases with cooling time due to additional production from the beta-decay of Pu-241 with a half-life of 14.3 years. The production rate of 241Am in conventional reactors, including its further accumulation through the decay of Pu-241 and its destruction through transmutation/incineration are very important parameters for the design of any recycling solution. In the present work, the Am-241(n,f) reaction cross-section was measured using Micromegas detectors at the Experimental Area 2 of the n_TOF facility at CERN. For the measurement, the U-235(n,f) and U-238(n,f) reference reactions were used for the determination of the neutron flux. In the present work an overview of the experimental setup and the adopted data analysis techniques is given along with preliminary results.European Union (European Social Fund-ESF) through the Operational Programme Human Resources Development, Education and Lifelong Learning MIS-5000432European Commission under the CHANDA project (7th Framework Programme

Monte Carlo simulations and n-p differential scattering data measured with Proton Recoil Telescopes

The authors wish to thank the National Center of the INFN for Research and Development in Information and Communication Technologies (CNAF) for their computational support.The neutron-induced fission cross section of U-235, a standard at thermal energy and between 0.15 MeV and 200 MeV, plays a crucial role in nuclear technology applications. The long-standing need of improving cross section data above 20 MeV and the lack of experimental data above 200 MeV motivated a new experimental campaign at the n_TOF facility at CERN. The measurement has been performed in 2018 at the experimental area 1 (EAR1), located at 185 m from the neutron-producing target (the experiment is presented by A. Manna et al. in a contribution to this conference). The U-235(n,f) cross section from 20 MeV up to about 1 GeV has been measured relative to the H-1(n,n)H-1 reaction, which is considered the primary reference in this energy region. The neutron flux impinging on the U-235 sample (a key quantity for determining the fission events) has been obtained by detecting recoil protons originating from n-p scattering in a C2H4 sample. Two Proton Recoil Telescopes (PRT), consisting of several layers of solid-state detectors and fast plastic scintillators, have been located at proton scattering angles of 25.07 degrees and 20.32 degrees, out of the neutron beam. The PRTs exploit the Delta E-E technique for particle identification, a basic requirement for the rejection of charged particles from neutron-induced reactions in carbon. Extensive Monte Carlo simulations were performed to characterize proton transport through the different slabs of silicon and scintillation detectors, to optimize the experimental set-up and to deduce the efficiency of the whole PRT detector. In this work we compare measured data collected with the PRTs with a full Monte Carlo simulation based on the Geant-4 toolkit

Measurement of the 14^{14}N(n,p)14^{14}C cross section at the CERN n_TOF facility from sub-thermal energy to 800 keV

Background: The $^{14}$N(n,p)$^{14}$C reaction is of interest in neutron capture therapy, where nitrogen-related dose is the main component due to low-energy neutrons, and in astrophysics, where 14N acts as a neutron poison in the s-process. Several discrepancies remain between the existing data obtained in partial energy ranges: thermal energy, keV region and resonance region. Purpose: Measuring the 14N(n,p)14C cross section from thermal to the resonance region in a single measurement for the first time, including characterization of the first resonances, and providing calculations of Maxwellian averaged cross sections (MACS). Method: Time-of-flight technique. Experimental Area 2 (EAR-2) of the neutron time-of-flight (n_TOF) facility at CERN. $^{10}$B(n,${\alpha}$)$^7$Li and $^{235}$U(n,f) reactions as references. Two detection systems running simultaneously, one on-beam and another off-beam. Description of the resonances with the R-matrix code sammy. Results: The cross section has been measured from sub-thermal energy to 800 keV resolving the two first resonances (at 492.7 and 644 keV). A thermal cross-section (1.809$\pm$0.045 b) lower than the two most recent measurements by slightly more than one standard deviation, but in line with the ENDF/B-VIII.0 and JEFF-3.3 evaluations has been obtained. A 1/v energy dependence of the cross section has been confirmed up to tens of keV neutron energy. The low energy tail of the first resonance at 492.7 keV is lower than suggested by evaluated values, while the overall resonance strength agrees with evaluations. Conclusions: Our measurement has allowed to determine the $^{14}$N(n,p) cross-section over a wide energy range for the first time. We have obtained cross-sections with high accuracy (2.5 %) from sub-thermal energy to 800 keV and used these data to calculate the MACS for kT = 5 to kT = 100 keV.Comment: 18 pages, 15 figures, 4 table

Neutron capture cross section measurements of Am-241 at the n_TOF facility

Neutron capture on Am-241 plays an important role in the nuclear energy production and also provides valuable information for the improvement of nuclear models and the statistical interpretation of the nuclear properties. A new experiment to measure the Am-241(n,gamma) cross section in the thermal region and the first few resonances below 10 eV has been carried out at EAR2 of the n_TOF facility at CERN. Three neutron-insensitive C6D6 detectors have been used to measure the neutron-capture gamma cascade as a function of the neutron time of flight, and then deduce the neutron capture yield. Preliminary results will be presented and compared with previously obtained results at the same facility in EAR1. In EAR1 the gamma-ray background at thermal energies was about 90% of the signal while in EAR2 is up to a 25 factor much more favorable signal to noise ratio. We also extended the low energy limit down to subthermal energies. This measurement will allow a comparison with neutron capture measurements conducted at reactors and using a different experimental technique

First results of the Th-230(n,f) cross section measurements at the CERN n_TOF facility

The study of neutron-induced reactions on actinides is of considerable importance for the design of advanced nuclear systems and alternative fuel cycles. Specifically, Th-230 is produced from the alpha-decay of U-234 as a byproduct of the Th-232/U-233 fuel cycle, thus the accurate knowledge of its fission cross section is strongly required. However, few experimental datasets exist in literature with large deviations among them, covering the energy range between 0.2 to 25 MeV. In addition, the study of the Th-230(n,f) cross-section is of great interest in the research on the fission process related to the structure of the fission barriers. Previous measurements have revealed a large resonance at E-n=715 keV and additional fine structures, but with high discrepancies among the cross-section values of these measurements. This contribution presents preliminary results of the Th-230(n,f) cross-section measurements at the CERN n_TOF facility. The high purity targets of the natural, but very rare isotope Th-230, were produced at JRC-Geel in Belgium. The measurements were performed at both experimental areas (EAR-1 and EAR-2) of the n_TOF facility, covering a very broad energy range from thermal up to at least 100 MeV. The experimental setup was based on Micromegas detectors with the U-235(n,f) and U-238(n,f) reaction cross-sections used as reference

Neutron capture measurement at the n TOF facility of the 204Tl and 205Tl s-process branching points

Neutron capture cross sections are one of the fundamental nuclear data in the study of the s (slow) process of nucleosynthesis. More interestingly, the competition between the capture and the decay rates in some unstable nuclei determines the local isotopic abundance pattern. Since decay rates are often sensible to temperature and electron density, the study of the nuclear properties of these nuclei can provide valuable constraints to the physical magnitudes of the nucleosynthesis stellar environment. Here we report on the capture cross section measurement of two thallium isotopes, $^{204}$Tl and $^{205}$Tl performed by the time-of-flight technique at the n TOF facility at CERN. At some particular stellar s-process environments, the decay of both nuclei is strongly enhanced, and determines decisively the abundance of two s-only isotopes of lead, $^{204}$Pb and $^{205}$Pb. The latter, as a long-lived radioactive nucleus, has potential use as a chronometer of the last s-process events that contributed to final solar isotopic abundances