The Copper-microRNA Pathway Is Integrated with Developmental and Environmental Stress Responses in Arabidopsis thaliana

As an essential nutrient, copper (Cu) scarcity causes a decrease in agricultural production. Cu deficiency responses include the induction of several microRNAs, known as Cu-miRNAs, which are responsible for degrading mRNAs from abundant and dispensable cuproproteins to economize copper when scarce. Cu-miRNAs, such as miR398 and miR408 are conserved, as well as the signal transduction pathway to induce them under Cu deficiency. The Arabidopsis thaliana SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) family member SPL7 binds to the cis-regulatory motifs present in the promoter regions of genes expressed under Cu deficiency, including Cu-miRNAs. The expression of several other SPL transcription factor family members is regulated by miR156. This regulatory miR156-SPL module plays a crucial role in developmental phase transitions while integrating internal and external cues. Here, we show that Cu deficiency also affects miR156 expression and that SPL3 overexpressing plants, resistant to miR156 regulation, show a severe decrease in SPL7-mediated Cu deficiency responses. These include the expression of Cu-miRNAs and their targets and is probably due to competition between SPL7 and miR156-regulated SPL3 in binding to cis-regulatory elements in Cu-miRNA promoters. Thus, the conserved SPL7-mediated Cu-miRNA pathway could generally be affected by the miR156-SPL module, thereby underscoring the integration of the Cu-miRNA pathway with developmental and environmental stress responses in Arabidopsis thaliana.</i

New Limits on Sterile Neutrinos from Suzaku Observations of the Ursa Minor Dwarf Spheroidal Galaxy

We present results of our search for X-ray line emission associated with the radiative decay of the sterile neutrino, a well-motivated dark matter candidate, in Suzaku Observatory spectra of the Ursa Minor dwarf spheroidal galaxy. These data represent the first deep observation of one of these extreme mass-to-light systems and the first dedicated dark matter search using an X-ray telescope. No such emission line is positively detected, and we place new constraints on the combination of the sterile neutrino mass and the active-sterile neutrino oscillation mixing angle. Line flux upper limits are derived using a maximum-likelihood-based approach that, along with the lack of intrinsic X-ray emission, enables us to minimize systematics and account for those that remain. The limits we derive match or approach the best previous results over the entire 1--20 keV mass range from a single Suzaku observation. These are used to place constraints on the existence of sterile neutrinos with given parameters in the general case and in the case where they are assumed to constitute all of the dark matter. The range allowed implies that sterile neutrinos remain a viable candidate to make up some -- or all -- of the dark matter and also explain pulsar kicks and various other astrophysical phenomena.Comment: revised to closely match version to be published in ApJ v. 69

Cost-Utility of Mindfulness-Based Stress Reduction for Fibromyalgia versus a Multicomponent Intervention and Usual Care: A 12-Month Randomized Controlled Trial (EUDAIMON Study)

Fibromyalgia (FM) is a prevalent, chronic, disabling, pain syndrome that implies high healthcare costs. Economic evaluations of potentially effective treatments for FM are needed. The aim of this study was to analyze the cost-utility of Mindfulness-Based Stress Reduction (MBSR) as an add-on to treatment-as-usual (TAU) for patients with FM compared to an adjuvant multicomponent intervention (FibroQoL) and to TAU. We performed an economic evaluation alongside a 12 month, randomized, controlled trial; data from 204 (68 per study arm) of the 225 patients (90.1%) were included in the cost-utility analyses, which were conducted both under the government and the public healthcare system perspectives. The main outcome measures were the EuroQol (EQ-5D-5L) for assessing Quality-Adjusted Life Years (QALYs) and improvements in health-related quality of life, and the Client Service Receipt Inventory (CSRI) for estimating direct and indirect costs. Incremental cost-effectiveness ratios (ICERs) were also calculated. Two sensitivity analyses (intention-to-treat, ITT, and per protocol, PPA) were conducted. The results indicated that MBSR achieved a significant reduction in costs compared to the other study arms (p < 0.05 in the completers sample), especially in terms of indirect costs and primary healthcare services. It also produced a significant incremental effect compared to TAU in the ITT sample (Delta QALYs = 0.053, p < 0.05, where QALYs represents quality-adjusted life years). Overall, our findings support the efficiency of MBSR over FibroQoL and TAU specifically within a Spanish public healthcare context

Fishing in Tidal Streams: New Radial Velocity and Proper Motion Constraints on the Orbit of the Anticenter Stream

We have obtained radial velocity measurements for stars in two, widely-separated fields in the Anticenter Stream. Combined with SDSS/USNO-B proper motions, the new measurements allow us to establish that the stream is on a nearly circular, somewhat inclined, prograde orbit around the Galaxy. While the orbital eccentricity is similar to that previously determined for the Monoceros stream, the sizes, inclinations, and positions of the orbits for the two systems differ significantly. Integrating our best fitting Anticenter Stream orbit forward, we find that it is closely aligned along and lies almost on top of a stream-like feature previously designated the "Eastern Banded Structure". The position of this feature coincides with the apogalacticon of the orbit. We tentatively conclude that this feature is the next wrap of the Anticenter Stream.Comment: 4 pages, 3 figures, 2 tables. Accepted for publication in ApJ Letter

Accurate Stellar Kinematics at Faint Magnitudes::application to the Bootes~I dwarf spheroidal galaxy

We develop, implement and characterise an enhanced data reduction approach which delivers precise, accurate, radial velocities from moderate resolution spectroscopy with the fibre-fed VLT/FLAMES+GIRAFFE facility. This facility, with appropriate care, delivers radial velocities adequate to resolve the intrinsic velocity dispersions of the very faint dSph dwarf galaxies. Importantly, repeated measurements let us reliably calibrate our individual velocity errors ($0.2 \leq \delta_V\leq 5$ km s$^{-1}$) and directly detect stars with variable radial velocities. We show, by application to the Bootes-1 dwarf spheroidal, that the intrinsic velocity dispersion of this system is significantly below 6.5\,km/s reported by previous studies. Our data favor a two-population model of Bootes-1, consisting of a majority `cold' stellar component, with velocity dispersion $2.4^{+0.9}_{-0.5}$\,km/s, and a minority `hot' stellar component, with velocity dispersion $\sim 9$\,km/s, although we can not completely rule out a single component distribution with velocity dispersion $4.6^{0.8}_{-0.6}$\,km/s. We speculate this complex velocity distribution actually reflects the distribution of velocity anisotropy in Bootes-1, which is a measure of its formation processes.Comment: ApJ in press. Anticipated publication July 1, 201

The large-scale structure of the halo of the Andromeda galaxy. I. Global stellar density, morphology and metallicity properties

We present an analysis of the large-scale structure of the halo of the Andromeda galaxy, based on the Pan-Andromeda Archeological Survey (PAndAS), currently the most complete map of resolved stellar populations in any galactic halo. Despite the presence

Annihilation vs. Decay: Constraining dark matter properties from a gamma-ray detection

Most proposed dark matter candidates are stable and are produced thermally in the early Universe. However, there is also the possibility of unstable (but long-lived) dark matter, produced thermally or otherwise. We propose a strategy to distinguish between dark matter annihilation and/or decay in the case that a clear signal is detected in gamma-ray observations of Milky Way dwarf spheroidal galaxies with gamma-ray experiments. The sole measurement of the energy spectrum of an indirect signal would render the discrimination between these cases impossible. We show that by examining the dependence of the intensity and energy spectrum on the angular distribution of the emission, the origin could be identified as decay, annihilation, or both. In addition, once the type of signal is established, we show how these measurements could help to extract information about the dark matter properties, including mass, annihilation cross section, lifetime, dominant annihilation and decay channels, and the presence of substructure. Although an application of the approach presented here would likely be feasible with current experiments only for very optimistic dark matter scenarios, the improved sensitivity of upcoming experiments could enable this technique to be used to study a wider range of dark matter models.Comment: 29 pp, 8 figs; replaced to match published version (minor changes and some new references

Dark Matter Direct Detection Signals inferred from a Cosmological N-body Simulation with Baryons

We extract at redshift z=0 a Milky Way sized object including gas, stars and dark matter (DM) from a recent, high-resolution cosmological N-body simulation with baryons. Its resolution is sufficient to witness the formation of a rotating disk and bulge at the center of the halo potential. The phase-space structure of the central galactic halo reveals the presence of a dark disk component, that is co-rotating with the stellar disk. At the Earth's location, it contributes to around 25% of the total DM local density, whose value is rho_DM ~ 0.37 GeV/cm^3. The velocity distributions also show strong deviations from pure Gaussian and Maxwellian distributions, with a sharper drop of the high velocity tail. We give a detailed study of the impact of these features on the predictions for DM signals in direct detection experiments. In particular, the question of whether the modulation signal observed by DAMA is or is not excluded by limits set by other experiments (CDMS, XENON and CRESST...) is re-analyzed and compared to the case of a standard Maxwellian halo, in both the elastic and the inelastic scattering scenarios. We find that the compatibility between DAMA and the other experiments is improved. In the elastic scenario, the DAMA modulation signal is slightly enhanced in the so-called channeling region, as a result of several effects. For the inelastic scenario, the improvement of the fit is mainly attributable to the departure from a Maxwellian distribution at high velocity.Comment: 39 page

Results of an Early Access Treatment Protocol of Daratumumab Monotherapy in Spanish Patients With Relapsed or Refractory Multiple Myeloma

Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16 mg/kg) was administered to 73 patients who had >= 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03-13.17) months, with a median number of 12 (range: 1-25) infusions. Grade 3/4 treatment-emergent adverse events were reported in 74% of patients and included lymphopenia (28.8%), thrombocytopenia (27.4%), neutropenia (21.9%), leukopenia (19.2%), and anemia (15.1%). Common (>5%) serious treatmentemergent adverse events included respiratory tract infection (9.6%), general physical health deterioration (6.8%), and back pain (5.5%). Infusion-related reactions occurred in 45% of patients. The median change from baseline in all domains of the EQ-5D-5L and EORTC QLQ-C30 was mostly 0. A total of 18 (24.7%) patients achieved a partial response or better, with 10 (13.7%) patients achieving a very good partial response or better. Median progression-free survival was 3.98 months. The results of this early access treatment protocol are consistent with previously reported trials of daratumumab monotherapy and confirm its safety and antitumoral efficacy in Spanish patients with heavily treated relapsed or refractory multiple myeloma

Siriusly, a newly identified intermediate-age Milky Way stellar cluster: a spectroscopic study of Gaia 1

We confirm the reality of the recently discovered Milky Way stellar cluster $\textit{Gaia}$ 1 using spectra acquired with the HERMES and AAOmega spectrographs of the Anglo-Australian Telescope. This cluster had been previously undiscovered due to its close angular proximity to Sirius, the brightest star in the sky at visual wavelengths. Our observations identified 41 cluster members, and yielded an overall metallicity of [Fe/H]$=-0.13\pm0.13$ and barycentric radial velocity of $v_r=58.30\pm0.22$ km/s. These kinematics provide a dynamical mass estimate of $12.9^{+4.6}_{-3.9}\times10^3$ M$_{\odot}$. Isochrone fits to $\textit{Gaia}$, 2MASS, and Pan-STARRS1 photometry indicate that $\textit{Gaia}$ 1 is an intermediate age ($\sim3$ Gyr) stellar cluster. Combining the spatial and kinematic data we calculate $\textit{Gaia}$ 1 has a circular orbit with a radius of about 12~kpc, but with a large out of plane motion: $z_\textrm{max}=1.1^{+0.4}_{-0.3}$ kpc. Clusters with such orbits are unlikely to survive long due to the number of plane passages they would experience.Comment: 9 pages (and 3 pages of appendices), 8 figures. Accepted to MNRA