TREX-DM: a low background Micromegas-based TPC for low mass WIMP detection

Dark Matter experiments are recently focusing their detection techniques in low-mass WIMPs, which requires the use of light elements and low energy threshold. In this context, we present the TREX-DM experiment, a low background Micromegas-based TPC for low-mass WIMP detection. Its main goal is the operation of an active detection mass $\sim$0.300 kg, with an energy threshold below 0.4 keVee and fully built with previously selected radiopure materials. This article describes the actual setup, the first results of the comissioning in Ar+2\%iC$_4$H$_{10}$ at 1.2 bar and the future updates for a possible physics run at the Canfranc Underground Laboratory in 2016. A first background model is also presented, based on Geant4 simulations and a muon/electron discrimination method. In a conservative scenario, TREX-DM could be sensitive to DAMA/LIBRA and other hints of positive WIMPs signals, with some space for improvement with a neutron/electron discrimination method or the use of other light gases.Comment: Proceedings of the 7th Symposium on Large TPCs for Low-Energy Rare Event Detectio

Tunable Graphene Electronics with Local Ultrahigh Pressure

We achieve fine tuning of graphene effective doping by applying ultrahigh pressures (> 10 GPa) using Atomic Force Microscopy (AFM) diamond tips. Specific areas in graphene flakes are irreversibly flattened against a SiO2 substrate. Our work represents the first demonstration of local creation of very stable effective p-doped graphene regions with nanometer precision, as unambiguously verified by a battery of techniques. Importantly, the doping strength depends monotonically on the applied pressure, allowing a controlled tuning of graphene electronics. Through this doping effect, ultrahigh pressure modifications include the possibility of selectively modifying graphene areas to improve their electrical contact with metal electrodes, as shown by Conductive AFM. Density Functional Theory calculations and experimental data suggest that this pressure level induces the onset of covalent bonding between graphene and the underlying SiO2 substrate. Our work opens a convenient avenue to tuning the electronics of 2D materials and van der Waals heterostructures through pressure with nanometer resolution

Nucleotides in neuroregeneration and neuroprotection

AbstractBrain injury generates the release of a multitude of factors including extracellular nucleotides, which exhibit bi-functional properties and contribute to both detrimental actions in the acute phase and also protective and reparative actions in the later recovery phase to allow neuroregeneration. A promising strategy toward restoration of neuronal function is based on activation of endogenous adult neural stem/progenitor cells. The implication of purinergic signaling in stem cell biology, including regulation of proliferation, differentiation, and cell death has become evident in the last decade. In this regard, current strategies of acute transplantation of ependymal stem/progenitor cells after spinal cord injury restore altered expression of P2X4 and P2X7 receptors and improve functional locomotor recovery. The expression of both receptors is transcriptionally regulated by Sp1 factor, which plays a key role in the startup of the transcription machinery to induce regeneration-associated genes expression. Finally, general signaling pathways triggered by nucleotide receptors in neuronal populations converge on several intracellular kinases, such as PI3K/Akt, GSK3 and ERK1,2, as well as the Nrf-2/heme oxigenase-1 axis, which specifically link them to neuroprotection. In this regard, regulation of dual specificity protein phosphatases can become novel mechanism of actions for nucleotide receptors that associate them to cell homeostasis regulation.This article is part of the Special Issue entitled ‘Purines in Neurodegeneration and Neuroregeneration’

Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity

Among the main complications associated with obesity are insulin resistance and altered glucose and lipid metabolism within the liver. It has previously been described that insulin receptor isoform A (IRA) favors glucose uptake and glycogen storage in hepatocytes compared with isoform B (IRB), improving glucose homeostasis in mice lacking liver insulin receptor. Thus, we hypothesized that IRA could also improve glucose and lipid metabolism in a mouse model of high-fatdiet-induced obesity. We addressed the role of insulin receptor isoforms in glucose and lipid metabolism in vivo. We expressed IRA or IRB specifically in the liver by using adeno-associated viruses (AAVs) in a mouse model of diet-induced insulin resistance and obesity. IRA, but not IRB, expression induced increased glucose uptake in the liver and muscle, improving insulin tolerance. Regarding lipid metabolism, we found that AAV-mediated IRA expression also ameliorated hepatic steatosis by decreasing the expression of Fasn, Pgc1a, Acaca and Dgat2 and increasing Scd-1 expression. Taken together, our results further unravel the role of insulin receptor isoforms in hepatic glucose and lipid metabolism in an insulin-resistant scenario. Our data strongly suggest that IRA is more efficient than IRB at favoring hepatic glucose uptake, improving insulin tolerance and ameliorating hepatic steatosis. Therefore, we conclude that a gene therapy approach for hepatic IRA expression could be a safe and promising tool for the regulation of hepatic glucose consumption and lipid metabolism, two key processes in the development of non-alcoholic fatty liver disease associated with obesity

Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA

Objective: To use deep sequencing to identify novel microRNAs in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate microRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3’-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. Results: We identified 990 known microRNAs and 1621 potential novel microRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate microRNAs were analysed further, of which 6 remained after northern blot analysis. Three novel microRNAs were regulated across models of chondrogenesis, chondrocyte differentiation or cartilage injury. One sequence (novel #11), annotated in rodents as microRNA-3085-3p, was preferentially expressed in cartilage, dependent on chondrocyte differentiation and, in man, is located in an intron of the cartilage-expressed gene CRTAC-1. This microRNA was shown to target the ITGA5 gene directly (which encodes integrin alpha5) and inhibited adhesion to fibronectin (dependent on alpha5beta1 integrin). Conclusion: Deep sequencing has uncovered many potential microRNA candidates expressed in human cartilage. At least three of these show potential functional interest in cartilage homeostasis and osteoarthritis. Particularly, novel #11 (microRNA-3085-3p) which has been identified for the first time in man

Neutrino Masses and Mixings from Supersymmetry with Bilinear R--Parity Violation: A Theory for Solar and Atmospheric Neutrino Oscillations

The simplest unified extension of the MSSM with bi-linear R--Parity violation naturally predicts a hierarchical neutrino mass spectrum, in which one neutrino acquires mass by mixing with neutralinos, while the other two get mass radiatively. We have performed a full one-loop calculation of the neutralino-neutrino mass matrix in the bi-linear \rp MSSM, taking special care to achieve a manifestly gauge invariant calculation. Moreover we have performed the renormalization of the heaviest neutrino, needed in order to get meaningful results. The atmospheric mass scale and maximal mixing angle arise from tree-level physics, while solar neutrino scale and oscillations follow from calculable one-loop corrections. If universal supergravity assumptions are made on the soft-supersymmetry breaking terms then the atmospheric scale is calculable as a function of a single \rp violating parameter by the renormalization group evolution due to the non-zero bottom quark Yukawa coupling. The solar neutrino problem must be accounted for by the small mixing angle (SMA) MSW solution. If these assumptions are relaxed then one can implement large mixing angle solutions, either MSW or just-so. The theory predicts the lightest supersymmetic particle (LSP) decay to be observable at high-energy colliders, despite the smallness of neutrino masses indicated by experiment. This provides an independent way to test this solution of the atmospheric and solar neutrino anomalies.Comment: 46 pages, references added + several misprints correcte

The spatial distribution of star and cluster formation in M51

Aims. We study the connection between spatially resolved star formation and young star clusters across the disc of M51. Methods. We combine star cluster data based on B, V, and I-band Hubble Space Telescope ACS imaging, together with new WFPC2 U-band photometry to derive ages, masses, and extinctions of 1580 resolved star clusters using SSP models. This data is combined with data on the spatially resolved star formation rates and gas surface densities, as well as Halpha and 20cm radio-continuum (RC) emission, which allows us to study the spatial correlations between star formation and star clusters. Two-point autocorrelation functions are used to study the clustering of star clusters as a function of spatial scale and age. Results. We find that the clustering of star clusters among themselves decreases both with spatial scale and age, consistent with hierarchical star formation. The slope of the autocorrelation functions are consistent with projected fractal dimensions in the range of 1.2-1.6, which is similar to other galaxies, therefore suggesting that the fractal dimension of hierarchical star formation is universal. Both star and cluster formation peak at a galactocentric radius of 2.5 and 5 kpc, which we tentatively attribute to the presence of the 4:1 resonance and the co-rotation radius. The positions of the youngest (<10 Myr) star clusters show the strongest correlation with the spiral arms, Halpha, and the RC emission, and these correlations decrease with age. The azimuthal distribution of clusters in terms of kinematic age away from the spiral arms indicates that the majority of the clusters formed 5-20 Myr before their parental gas cloud reached the centre of the spiral arm.Comment: 14 pages, 21 figures, accepted for publication in A&