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Supplementary Table 1 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

Supplementary Figure 5 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

Supplementary Figure 3 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

Supplementary Figure 4 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

Supplementary Table 3 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

Supplementary Table 2 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

Sustained activation of extracellular signal-regulated kinase (ERK) has been detected previously in numerous tumors in the absence of RAS-activating mutations. However, the molecular mechanisms responsible for ERK-unrestrained activity independent of RAS mutations remain unknown. Here, we evaluated the effects of the functional interactions of ERK proteins with dual-specificity phosphatase 1 (DUSP1), a specific inhibitor of ERK, and S-phase kinase-associated protein 2 (SKP2)/CDC28 protein kinase 1b (CKS1) ubiquitin ligase complex in human hepatocellular carcinoma (HCC). Levels of DUSP1, as assessed by real-time reverse transcription–PCR and Western blot analysis, were significantly higher in tumors with better prognosis (as defined by the length of patients' survival) when compared with both normal and nontumorous surrounding livers, whereas DUSP1 protein expression sharply declined in all HCC with poorer prognosis. In the latter HCC subtype, DUSP1 inactivation was due to either ERK/SKP2/CKS1-dependent ubiquitination or promoter hypermethylation associated with loss of heterozygosity at the DUSP1 locus. Noticeably, expression levels of DUSP1 inversely correlated with those of activated ERK, as well as with proliferation index and microvessel density, and directly with apoptosis and survival rate. Subsequent functional studies revealed that DUSP1 reactivation led to suppression of ERK, CKS1, and SKP2 activity, inhibition of proliferation and induction of apoptosis in human hepatoma cell lines. Taken together, the present data indicate that ERK achieves unrestrained activity during HCC progression by triggering ubiquitin-mediated proteolysis of its specific inhibitor DUSP1. Thus, DUSP1 may represent a valuable prognostic marker and ERK, CKS1, or SKP2 potential therapeutic targets for human HCC. [Cancer Res 2008;68(11):4192–200]

Supplementary Figure 2 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

Supplementary Figure 1 from Dual-Specificity Phosphatase 1 Ubiquitination in Extracellular Signal-Regulated Kinase–Mediated Control of Growth in Human Hepatocellular Carcinoma

The 130Te(20Ne,20O)130Xe double charge exchange reaction was measured for the first time at very forward angles with the MAGNEX magnetic spectrometer at INFN-LNS. The study, performed at beam energy of 306 MeV, is part of a systematic exploration promoted by the NUMEN project. The last aims to measure specific reaction cross sections to provide experimentally driven information about nuclear matrix elements of interest in the context of neutrinoless double beta decay.

Comparing populations across temperature gradients can inform how global warming will impact the structure and function of ecosystems. Shoot density, morphometry and productivity of the seagrass Posidonia oceanica to temperature variation was quantified at eight locations in Sardinia (western Mediterranean Sea) along a natural sea surface temperature (SST) gradient. The locations are spanned for a narrow range of latitude (1.5°), allowing the minimization of the effect of eventual photoperiod variability. Mean SST predicted P. oceanica meadow structure, with increased temperature correlated with higher shoot density, but lower leaf and rhizome width, and rhizome biomass. Chlorophyll a (Chl-a) strongly impacted seagrass traits independent of SST. Disentangling the effects of SST and Chl-a on seagrass meadow density revealed that they work independently, but in the same direction with potential synergism.Space-for-time substitution predicts that global warming will trigger denser seagrass meadows with slender shoots, fewer leaves, and strongly impact seagrass ecosystem. Future investigations should evaluate if global warming will erode the ecosystem services provided by seagrass meadows.

International audience; The possibility to use a special class of heavy-ion induced direct reactions, such as double charge exchange reactions, is discussed in view of their application to extract information that may be helpful to determinate the nuclear matrix elements entering in the expression of neutrinoless double beta decay half-life. The strategies adopted in the experimental campaigns performed at INFN - Laboratori Nazionali del Sud are briefly described, emphasizing the advantages of the multi-channel approach to nuclear reaction data analysis.

In this work, the consequences of a local gorgonian coral mortality on the whole coralligenous assemblage were studied. A Before/After-Control/Impact sampling design was used: the structure of the coralligenous assemblage was compared before and after the gorgonian mortality event at the mortality site and two control sites. At the mortality site, a relevant decrease in alpha and beta diversity occurred, with a shift from a stratified assemblage characterized by gorgonians and other invertebrates to an assemblage dominated by algal turfs, conversely, neither significant variations of the structure nor decrease in biodiversity were observed at the control sites. The assemblage shift involved the main taxa in different times: in autumn 2018, a large proportion of the plexaurid coral Paramuricea clavata died, but no significant changes were observed in the structure of the remaining assemblage. Then, in autumn 2019, algal turfs increased significantly and, one year later, the abundance of the gorgonian Eunicella cavolini and bryozoans collapsed. Although the mechanisms of the assemblage shift following gorgonian loss will remain uncertain and a cause-effect relationship cannot be derived, results suggest the need for detecting signs of gorgonian forests stress in monitoring programs, which should be considered early indicators of their condition. in the coralligenous monitoring programs for detecting any sign of gorgonian forests stress which should be considered an early indicator of the assemblage condition.

The search for neutrinoless double-beta (0νββ) decay is currently a key topic in physics, due to its possible wide implications for nuclear physics, particle physics, and cosmology. The NUMEN project aims to provide experimental information on the nuclear matrix elements (NMEs) that are involved in the expression of 0νββ decay half-life by measuring the cross section of nuclear double-charge exchange (DCE) reactions. NUMEN has already demonstrated the feasibility of measuring these tiny cross sections for some nuclei of interest for the 0νββ using the superconducting cyclotron (CS) and the MAGNEX spectrometer at the Laboratori Nazionali del Sud (LNS.) Catania, Italy. However, since the DCE cross sections are very small and need to be measured with high sensitivity, the systematic exploration of all nuclei of interest requires major upgrade of the facility. R&amp, D for technological tools has been completed. The realization of new radiation-tolerant detectors capable of sustaining high rates while preserving the requested resolution and sensitivity is underway, as well as the upgrade of the CS to deliver beams of higher intensity. Strategies to carry out DCE cross-section measurements with high-intensity beams were developed in order to achieve the challenging sensitivity requested to provide experimental constraints to 0νββ NMEs.

International audience; The NUMEN experimental activity with accelerated beams is performed at INFN–Laboratori Nazionali del Sud (LNS) in Catania using the Superconducting Cyclotron and the MAGNEX magnetic spectrometer. The scientific motivation of NUMEN is to extract experiment-driven information on the nuclear matrix elements entering in the expression of the 0νββ decay half-life. The reaction cross sections involved, especially for the double charge exchange process, are very low, thus limiting the present exploration to a few selected isotopes of interest in the context of typically low-yield experimental runs. In order to make feasible a systematic study of all the candidate nuclei, a major upgrade of the LNS facility is foreseen to increase the experimental yield by more than two orders of magnitude. To this purpose, frontier technologies are being developed for the accelerator and the detection systems. An updated description of the choices derived from the recent R&D activity on the target system and MAGNEX focal plane detector is given.

The40Ca(18O,18F)40K single charge exchange (SCE) reaction is explored at an incident energy of 275 MeV and analyzed consistently by collecting the elastic scattering and inelastic scattering data under the same experimental conditions. Full quantum-mechanical SCE calculations of the direct mechanism are performed by including microscopic nuclear structure inputs and adopting either a bare optical potential or a coupled channel equivalent polarization potential (CCEP) constrained by the elastic and inelastic data. The direct SCE mechanism describes the magnitude and shape of the angular distributions rather well, thus suggesting the suppression of sequential multi-nucleon transfer processes.

NUMEN proposes an innovative technique to access the nuclear matrix elements entering the expression of the lifetime of the double beta decay by cross-section measurements of heavy-ion induced Double Charge Exchange (DCE) reactions. Despite the fact that the two processes, namely neutrinoless double beta decay and DCE reactions, are triggered by the weak and strong interaction respectively, important analogies are suggested. The basic point is the coincidence of the initial and final state many-body wave functions in the two types of processes and the formal similarity of the transition operators. The main experimental tools for this project are the K800 Superconducting Cyclotron and MAGNEX spectrometer at the INFN-LNS laboratory. However, the tiny values of DCE cross-sections and the resolution requirements demand beam intensities much higher than those manageable with the present facility. The on-going upgrade of the INFN-LNS facilities promoted by the POTLNS a project in this perspective is intimately connected to the NUMEN project. This paper describes the solutions proposed as a result of the R&D activity performed during the recent years. The goal is to develop suitable technologies allowing for the measurements of DCE cross-section under extremely high beam intensities. a PIR01_00005 — potenziamento dell’infrastruttura di ricerca Laboratori Nazionali del Sud per la produzione di fasci di ioni ad alta intensitá.

To search for the production of a dark photon ($A^{\prime} $) in the process ${e}^{+}{e}^{-}\to A^{\prime} \gamma $, the PADME apparatus has been built athe INFN Laboratori Nazionali di Frascati. It is a small-scale detector consisting of an active target, a beam monitor system, a spectrometer to measure charged particle momenta in the range 50–400 MeV, a dipole magnet to deflect the primary positron beam out of the spectrometer and allow charged particle momentum analysis and an electromagnetic calorimetric system to detect signal and background photons produced in the annihilations with high accuracy. Each element has specific requirements that are stringent and sometimes at the limit of present technology. This proceeding will give an overview of each component and a description of the technical solutions implemented to accomplish the experiment needs. Results of the commissioning data taking, performed from October 2018 to February 2019, will be illustrated.

The 18O+48Ti reaction was studied at the energy of 275 MeV for the first time under the NUMEN and NURE experimental campaigns with the aim to investigate the complete net of reaction channels potentially involved in the 48Ca→48Ti double charge exchange transition. Such a transition is of great interest because of its relevance to the extraction of 48Ca→48Ti double beta decay nuclear matrix element. The relevant experiment was carried out at the MAGNEX facility of INFN-LNS in Catania. Angular distribution measurements for the various reaction products were performed by using the MAGNEX large acceptance magnetic spectrometer. The present contribution is focused on the analysis of the one-proton transfer channel with emphasis on the particle identification technique and the estimation of background contaminations.

Double charge exchange (DCE) reactions could provide experimentally driven information about nuclear matrix elements of interest in the context of neutrinoless double-β decay. To achieve this goal, a detailed description of the reaction mechanism is mandatory. This requires the full characterization of the initial and final-state interactions, which are poorly known for many of the projectile-target systems involved in future DCE studies. Among these, we intend to study the 20Ne + 130Te and 18O + 116Sn systems at 15.3 AMeV, which are particularly relevant due to their connection with the 130Te→130Xe and 116Cd→116Sn double-β decays. We measure the elastic and inelastic scattering cross-section angular distributions and compare them with theoretical calculations performed in the optical model, one-step distorted wave Born approximation, and coupled-channel approaches using the São Paulo double-folding optical potential. A good description of the experimental data in the whole explored range of transferred momenta is obtained provided that couplings with the 21+ states of the projectile and target are explicitly included within the coupled-channel approach. These results are relevant also in the analysis of other quasi-elastic reaction channels in these systems, in which the same couplings should be included.

Background: Heavy-ion induced two-nucleon transfer reactions are powerful tools to reveal peculiar aspects of the atomic nucleus, such as pairing correlations, single-particle and collective degrees of freedom, and more. Also, these processes are in competition with the direct meson exchange in the double charge exchange reactions, which have recently attracted great interest due to their possible connection to neutrinoless double-beta decay. In this framework, the exploration of two-nucleon transfer reactions in the 20Ne+116Cd collision at energies above the Coulomb barrier is particularly relevant since the 116Cd nucleus is a candidate for the double-beta decay. Methods: We measured the excitation energy spectra and absolute cross sections for the two reactions using the MAGNEX large acceptance magnetic spectrometer to detect the ejectiles. We performed direct coupled reaction channels and sequential distorted wave Born approximation calculations using the double folding S\~ao Paulo potential to model the initial and final state interactions. The spectroscopic amplitudes for two- and singleparticle transitions were derived by different nuclear structure approaches: microscopic large-scale shell model, interacting boson model-2 and quasiparticle random phase approximation. Results: The calculations are able to reproduce the experimental cross sections for both two-neutron and twoproton transfer reactions. The role of couplings with the inelastic channels are found to be important in the two-proton transfer case. A competition between the direct and the sequential process is found in the reaction mechanism. For the two-proton transfer case, the inclusion of the 1g7/2 and 2d5/2 orbitals in the model space is crucial.

Predicting community-level responses to seawater warming is a pressing goal of global change ecologists. How far such predictions can be derived from a fine gradient of thermal environments needs to be explored, even if ignoring water climatology does not allow estimating subtidal marine heat waves. In this study insights about the influence of the thermal environment on the coralligenous community structure were gained by considering sites (Sardinia, Italy) at different temperature conditions. Heating events were measured (by loggers at 18 m, 23 m, 28 m, 33 m and 38 m deep) and proxies for their duration (the maximum duration of events warmer than the 90th percentile temperature), intensity (the median temperature) and variability (the number of daily ΔT larger than the mean daily ΔT, and the number of heating events larger in ΔT than the 90th percentile ΔT) were selected by GAM models. Reliable predictions of decrease in coralligenous richness of taxa/morphological groups, with relevant increment in turfs and encrusting coralline algae abundance at the expenses of bryozoans were made. Associations to the different types of heating descriptor have highlighted the aspect (intensity, duration or variability) of the heating events and the threshold for each of them responsible for the trajectories of change.

The NUMEN project at Laboratori Nazionali del Sud of INFN studies the nuclear matrix elements of Double Charge Exchange reactions between some particular nuclei. This information will be helpful in studying the Neutrinoless Double Beta decay. Because of the very low cross-sections of such reactions, high statistics must be acquired using very intense ion beams coupled with thin targets in order to get a good resolution in energy measurements. Since the target is irradiated with low energy and intense ion beams the crucial problems are the large amount of released heat and the activation of the material. To cope with the first problem isotopes are evaporated on a graphite substrate with high thermal conductivity that will be cooled down using a cryocooler. The second issue demands for an automatic system for the target handling during the data taking of the experiment. Positioning of the target-holder with appropriate precision and contact force is a special requirement, while all materials have to be selected to suit both the large temperature range and the foreseen radiation level. This work focuses on the automatic system for target manipulation, describing its design characteristics to cope with such particular working condition and to be integrated in the experiment.

International audience; In the NUMEN Experiment, Double Charge Exchange (DCE) reactions will be studied to get very precise measurements of their cross sections and final state levels. The interest for these reactions lies in the possibility for some nuclides to have DCE with initial and final states identical to those of the Neutrinoless Double β-Decay. To reach a good precision in the energy measurements, high statistics is needed and severe constraints about the target thickness must be satisfied. A 50 μA intense ion beam will provide the desired statistics, while posing the problem of dissipating the massive heat generated in the target. It is therefore necessary to design a suitable cooling system, which must affect the particles’ energy as little as possible. Said energy is already influenced by the current setup. The Superconducting Cyclotron (SC) and the MAGNEX Spectrometer introduce an error on the particles’ energy by 1/1000th (FWHM value) of its average energy. In the target, the main sources of error are straggling of projectiles and reaction products, and the dispersion effect. Both closely depend on the target thickness, which must be of the order of few hundred nanometres. In addition, the two effects are worsened if the target thickness is not uniform. The solution to these problems has been found by backing the target isotope with relatively thin substrate of Highly Oriented Pyrolytic Graphite (HOPG). Its thermodynamic properties fit the cooling requirements and can be as thin as 450 μg cm−2. The further straggling suffered by the ejectiles is tolerable, falling within the resolution requirements. Samples are deposited by using Electron Beam Evaporation: results obtained for Sn and Te are checked by Scanning Electron Microscopy (SEM). A quantitative evaluation of the samples’ thickness has been performed by Alpha-Particle Transmission (APT) and Rutherford Backscattering Spectrometry (RBS) measurements. A Monte Carlo code has been implemented to estimate the ejectiles energy distribution using the experimental measurements as input. Results from characterization and simulations help in optimizing the target thickness and the energy resolution of reaction products.

The great success of the Standard Model has reached its maximum with the Higgs boson discovery. However, several anomalies observed in the universe when applying the gravitational theory, lead to believe that the visible matter is not the only constituent of the universe. A new matter component, called dark matter, must be introduced through an extension of the Standard Model. A simple scenario consisting in adding a new gauge symmetry U D (1) and, as a consequence, a new (massive) gauge boson, the dark photon A′. PADME is a new experiment of the Laboratori Nazionali di Frascati searching for the A′, decaying invisibly, produced in the fixed target annihilation e+e − → γA′. The technique used by the experiment to probe the dark photon hypothesis is the missing mass method. The PADME experiment took data in two runs. Some preliminary highlights from the ongoing data analysis effort are presented.

Estimating spatial patterns of variability in coastal marine priority habitats may allow to plan monitoring programs and impact evaluation studies and to optimize sampling designs in environmental investigations. In this study the spatial variability of the vertical distribution (18 m, 23 m, 28 m, 33 m, and 38 m of depth) of coralligenous cliff assemblages was estimated in three marine biogeographic areas of the Mediterranean Sea: the Sardinia Sea, the Tyrrhenian Sea and the Bonifacio Strait. Sampling sites were selected in the West, North, and East coast of Sardinia, all in pristine conditions (far from any anthropogenic sources of influence and in highly oligothrophic water). Important variations among areas in the vertical zonation of the coralligenous cliffs have emerged, especially at the shallower depths, and the dominant taxa have been highlighted. Despite these unconsistencies, a common increase in the number of taxa/groups per sample was found with depth. Thermal environment and hydrodynamics have been discussed as the most likely important drivers of such variability. Overall, these data support the hypothesis that coralligenous cliff assemblages unaffected by local anthropogenic disturbance may be relevantly different in structure and indicate that the lack of gorgonians and bryozoans (commonly used as ecological indicators) is not necessarily a sign of local human impact, as it may be the result of biogeographic patterns.

The present study aims at contributing to the knowledge of the spatial variability of coralligenous reefs through the evaluation of patterns ranging from local to biogeographic scale around the island of Sardinia. The coralligenous reef assemblages of six areas were studied through a hierarchical sampling design: three sites per area were selected, in each site three plots were sampled and in each plot ten photographic samples were collected. The structure of coralligenous reefs across closed biogeographic regions is described, highlighting that nearly pristine assemblages, although characterized by similar high diversity, can be either dominated by animals, such as gorgonians and bryozoans, or macroalgae. The observed variations seem largely related to biogeographic patterns rather than spatial distance, supporting the need to identify specific reference conditions to assess the ecological quality of this habitat depending on the biogeographic area to be monitored.

Results of the study of structural and optical properties of Cu2ZnSn(S,Se)4 thin films obtained by sulfitation (selenization) of Cu2ZnSn films which were sputtered by target direct current magnetron sputtering using a stoichiometric Cu2ZnSn (99.99%) target are presented. It has been found that Cu2ZnSn(S,Se)4 thin films are polycrystalline with a grain size of ~60 nm. The optical bandgap of Cu2ZnSnS4 (E op = 1.65 eV) and Cu2ZnSnSe4 (R op = 1.2 eV) thin films have been determined.

Optical properties of thin Cu2ZnSnS4 films produced by RF magnetron sputtering of preliminarily synthesized material are studied. Transmission and reflection coefficients are studied in a range from 0.4 to 26 μm. The optical band-gap width depending on substrate temperature is estimated; in optimal modes, it is equal to 1.47 eV. The study of electrical properties shows that Cu2ZnSnS4 possesses low charge-carrier mobility, μ = 1.9 cm2/(V s), at room temperature and hole concentration р = 5 × 1018 cm–3. Electron microscopy shows that the film possesses a polycrystalline structure with a crystallite size on the order of 100 nm.