4MOST Consortium Survey 3: Milky Way Disc and Bulge Low-Resolution Survey (4MIDABLE-LR)

The mechanisms of the formation and evolution of the Milky Way are encoded in the orbits, chemistry and ages of its stars. With the 4MOST MIlky way Disk And BuLgE Low-Resolution Survey (4MIDABLE-LR) we aim to study kinematic and chemical substructures in the Milky Way disc and bulge region with samples of unprecedented size out to larger distances and greater precision than conceivable with Gaia alone or any other ongoing or planned survey. Gaia gives us the unique opportunity for target selection based almost entirely on parallax and magnitude range, hence increasing the efficiency in sampling larger Milky Way volumes with well-defined and effective selection functions. Our main goal is to provide a detailed chrono-chemo-kinematical extended map of our Galaxy and the largest Gaia follow-up down to $G = 19$ magnitudes (Vega). The complex nature of the disc components (for example, large target densities and highly structured extinction distribution in the Milky Way bulge and disc area), prompted us to develop a survey strategy with five main sub-surveys that are tailored to answer the still open questions about the assembly and evolution of our Galaxy, while taking full advantage of the Gaia data.Comment: Part of the 4MOST issue of The Messenger, published in preparation of 4MOST Community Workshop, see http://www.eso.org/sci/meetings/2019/4MOST.htm

The Pristine Inner Galaxy Survey (PIGS) VII: a discovery of the first inner Galaxy CEMP-r/s star

Well-studied very metal-poor (VMP, [Fe/H] < -2 ) stars in the inner Galaxy are few in number, and they are of special interest because they are expected to be among the oldest stars in the MilkyWay. We present high-resolution spectroscopic follow-up of the carbon-enhanced metal-poor (CEMP) star Pristine_184237.56-260624.5 (hereafter Pr184237) identified in the Pristine Inner Galaxy Survey. This star has an apocentre of about 2 kpc. Its atmospheric parameters (Teff = 5100 K, log g = 2.0, [Fe/H] = -2.60) were derived based on the non-local thermodynamic equilibrium (NLTE) line formation. We determined abundances for 32 elements, including 15 heavy elements beyond the iron group. The NLTE abundances were calculated for 13 elements from Na to Pb. Pr184237 is strongly enhanced in C, N, O, and both s- and r-process elements from Ba to Pb; it reveals a low carbon isotope ratio of 12C/13C = 7. The element abundance pattern in the Na-Zn range is typical of halo stars. With [Ba/Eu] = 0.32, Pr184237 is the first star of the CEMP-r/s subclass identified in the inner Galaxy. Variations in radial velocity suggest binarity. We tested whether a pollution by the s- or i-process material produced in the more massive and evolved companion can form the observed abundance pattern and find that an i-process in the asymptotic giant branch star with a progenitor mass of 1.0-2.0 Msun can be the solution.Comment: 15 pages, 11 figures, 5 tables, MNRAS, accepte

Modelling simple stellar populations in the near-ultraviolet to near-infrared with the X-shooter Spectral Library (XSL)

We present simple stellar population models based on the empirical X-shooter Spectral Library (XSL) from NUV to NIR wavelengths. The unmatched characteristics of relatively high resolution and extended wavelength coverage ($350-2480$ nm, $R\sim10\,000$) of the XSL population models bring us closer to bridging optical and NIR studies of intermediate and old stellar populations. It is now common to find good agreement between observed and predicted NUV and optical properties of stellar clusters due to our good understanding of the main-sequence and early giant phases of stars. However, NIR spectra of intermediate-age and old stellar populations are sensitive to cool K and M giants. The asymptotic giant branch, especially the thermally pulsing asymptotic giant branch, shapes the NIR spectra of $0.5-2$ Gyr old stellar populations; the tip of the red giant branch defines the NIR spectra of populations with ages larger than that. We construct sequences of the average spectra of static giants, variable-rich giants, and C-rich giants to include in the models separately. The models span the metallicity range $-2.2<[Fe/H]<+0.2$ and ages above 50 Myr, a broader range in the NIR than in other models based on empirical spectral libraries. Our models can reproduce the integrated optical colours of the Coma cluster galaxies at the same level as other semi-empirical models found in the literature. In the NIR, there are notable differences between the colours of the models and Coma cluster galaxies. The XSL models expand the range of predicted values of NIR indices compared to other models based on empirical libraries. Our models make it possible to perform in-depth studies of colours and spectral features consistently throughout the optical and the NIR range to clarify the role of evolved cool stars in stellar populations.Comment: 30 pages, 26 figures, accepted to Astronomy & Astrophysics, models will be available on http://xsl.astro.unistra.fr/ upon publishin

Patient satisfaction in treatment of non-complex fractures and dislocations in general practice in the Netherlands:prospective cohort study protocol

INTRODUCTION: Diagnosis and treatment of fractures and dislocations are mostly performed in hospital settings. However, equal care for patients with non--complex fractures or dislocations ('minor trauma care') may be provided in general practice. While substitution of care from secondary to primary care settings is stimulated by governments and insurers, it is unknown what the effects are on patient satisfaction level. Therefore, our primary objective is to determine the effect of minor trauma care delivered in a general practice as compared with a hospital on patient satisfaction. Secondary objectives are to assess the effects on treatment outcomes, cost-effectiveness and time consumption. METHODS AND ANALYSIS: In a prospective cohort study, we will include 200 patients aged 12 and over with an X-ray confirmed diagnosis of a non--complex fracture or dislocation out of whom 100 treated in a general practice and 100 in a secondary care hospital, both located in the Netherlands. All treatment procedures and follow-up will be done in accordance to the hospital's standards of trauma care. Study assessments will be performed pre-treatment, and 1, 6 and 12 weeks after treatment. Data collected include demographics, patient satisfaction and patient-reported outcomes including physical functioning, complications, pain scores and treatment-related costs. The primary outcome patient satisfaction measured at 12 weeks will be compared between the settings and additionally multivariable regression will be performed to assess potential confounding effects of unbalanced prognostic factors. Treatment outcomes and time consumption will be analysed following the same approach while cost-effectiveness will be assessed using an incremental cost-effectiveness ratio. Subsequently, results will be discussed using focus groups consisting of patients (n=15) and healthcare providers. ETHICS AND DISSEMINATION: The Medical Ethics Committee from the University Medical Center Groningen reviewed this study protocol and granted exemption from ethical approval (METc UMCG 2017/277). Study results will be presented at (inter)national conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03506958; Pre-results

Molecular data show conserved DNA locations distinguishing lung cancer subtypes and regulation of immune genes

Introduction: Non-small-cell lung cancer exhibits a range of transcriptional and epigenetic patterns that not only define distinct phenotypes, but may also govern immune related genes, which have a major impact on survival. Methods: We used open-source RNA expression and DNA methylation data of the Cancer Genome Atlas with matched non-cancerous tissue to evaluate whether these pretreatment molecular patterns also influenced genes related to the immune system and overall survival. Results: The distinction between lung adenocarcinoma and squamous c

Molecular targets for the protodynamic action of cis-urocanic acid in human bladder carcinoma cells

<p>Abstract</p> <p>Background</p> <p>cis-urocanic acid (cis-UCA) is an endogenous amino acid metabolite capable of transporting protons from the mildly acidic extracellular medium into the cell cytosol. The resulting intracellular acidification suppresses many cellular activities. The current study was aimed at characterizing the molecular mechanisms underlying cis-UCA-mediated cytotoxicity in cultured cancer cells.</p> <p>Methods</p> <p>5367 bladder carcinoma cells were left untreated or treated with cis-UCA. Cell death was assessed by measuring caspase-3 activity, mitochondrial membrane polarization, formation and release of cytoplasmic histone-associated DNA fragments, and cellular permeabilization. Cell viability and metabolic activity were monitored by colorimetric assays. Nuclear labelling was used to quantify the effects of cis-UCA on cell cycle. The activity of the ERK and JNK signalling pathways was studied by immunoblotting with specific antibodies. Phosphatase activity in cis-UCA-treated cells was determined by assay kits measuring absorbance resulting from the dephosphorylation of an artificial substrate. All statistical analyses were performed using the two-way Student's t-test (p < 0.05).</p> <p>Results</p> <p>Here we report that treatment of the 5637 human bladder carcinoma cells with 2% cis-UCA induces both apoptotic and necrotic cell death. In addition, metabolic activity of the 5637 cells is rapidly impaired, and the cells arrest in cell cycle in response to cis-UCA. Importantly, we show that cis-UCA promotes the ERK and JNK signalling pathways by efficiently inhibiting the activity of serine/threonine and tyrosine phosphatases.</p> <p>Conclusions</p> <p>Our studies elucidate how cis-UCA modulates several cellular processes, thereby inhibiting the proliferation and survival of bladder carcinoma cells. These anti-cancer effects make cis-UCA a potential candidate for the treatment of non-muscle invasive bladder carcinoma.</p

The Pristine Dwarf-Galaxy survey - II. In-depth observational study of the faint Milky Way satellite Sagittarius II

We present an extensive study of the Sagittarius II (Sgr II) stellar system using MegaCam g and i photometry, narrow-band, metallicity-sensitive calcium H&K doublet photometry and Keck II/DEIMOS multiobject spectroscopy. We derive and refine the Sgr II structural and stellar properties inferred at the time of its discovery. The colour–magnitude diagram implies Sgr II is old (12.0 ± 0.5 Gyr) and metal poor. The CaHK photometry confirms the metal-poor nature of the satellite ([Fe/H] CaHK = −2.32 ± 0.04 dex) and suggests that Sgr II hosts more than one single stellar population (σ CaHK [FeH] = 0.11+0.05 −0.03 dex). Using the Ca infrared triplet measured from our highest signal-to-noise spectra, we confirm the metallicity and dispersion inferred from the Pristine photometric metallicities ([Fe/H]spectro = −2.23 ± 0.05 dex, σspectro [Fe/H] = 0.10+0.06 −0.04 dex). The velocity dispersion of the system is found to be σv = 2.7+1.3 −1.0 km s−1 after excluding two potential binary stars. Sgr II’s metallicity and absolute magnitude (MV = −5.7 ± 0.1 mag) place the system on the luminosity–metallicity relation of the Milky Way dwarf galaxies despite its small size. The low but resolved metallicity and velocity dispersions paint the picture of a slightly dark-matter-dominated satellite (M/L = 23.0+32.8 −23.0 M L−1 ). Furthermore, using the Gaia Data Release 2, we constrain the orbit of the satellite and find an apocentre of 118.4+28.4 −23.7 kpc and a pericentre of 54.8+3.3 −6.1 kpc. The orbit of Sgr II is consistent with the trailing arm of the Sgr stream and indicates that it is possibly a satellite of the Sgr dSph that was tidally stripped from the dwarf’s influence.ES, KY, and AA gratefully acknowledge funding by the Emmy Noether programme from the Deutsche Forschungsgemeinschaft (DFG). This work has been published under the framework of the IdEx Unistra and benefits from a funding from the state managed by theFrench National Research Agency as part of the investments for the future program. NFM, RI, and NL gratefully acknowledge support from the French National Research Agency (ANR) funded project ‘Pristine’ (ANR-18-CE31-0017) along with funding from CNRS/INSU through the Programme National Galaxies et Cosmologie and through the CNRS grant PICS07708. The authors thank the International Space Science Institute (ISSI), Berne, Switzerland for providing financial support and meeting facilities to the international team ‘Pristine’. JIGH acknowledges financial support from the Spanish Ministry project MINECO AYA2017- 86389-P, and from the Spanish MINECO under the 2013 Ramon y ´ Cajal program MINECO RYC-2013-14875. BPML gratefully acknowledges support from FONDECYT postdoctoral fellowship No. 316051

GHOST Commissioning Science Results II: a very metal-poor star witnessing the early Galactic assembly

This study focuses on Pristine$\_180956.78$$-$$294759.8$ (hereafter P180956, [Fe/H] $=-1.95\pm0.02$), a star selected from the Pristine Inner Galaxy Survey (PIGS), and followed-up with the recently commissioned Gemini High-resolution Optical SpecTrograph (GHOST) at the Gemini South telescope. The GHOST spectrograph's high efficiency in the blue spectral region ($3700-4800$~\AA) enables the detection of elemental tracers of early supernovae (e.g. Al, Mn, Sr, Eu), which were not accessible in the previous analysis of P180956. The star exhibits chemical signatures resembling those found in ultra-faint dwarf systems, characterised by very low abundances of neutron-capture elements (Sr, Ba, Eu), which are uncommon among stars of comparable metallicity in the Milky Way. Our analysis suggests that P180956 bears the chemical imprints of a small number (2 or 4) of low-mass hypernovae (\sim10-15\msun), which are needed to reproduce the abundance pattern of the light-elements (e.g. [Si, Ti/Mg, Ca] $\sim0.6$), and one fast-rotating intermediate-mass supernova (\sim300\kms, \sim80-120\msun). Both types of supernovae explain the high [Sr/Ba] of P180956 ($\sim1.2$). The small pericentric (\sim0.7\kpc) and apocentric (\sim13\kpc) distances and its orbit confined to the plane (\lesssim 2\kpc), indicate that this star was likely accreted during the early Galactic assembly phase. Its chemo-dynamical properties suggest that P180956 formed in a system similar to an ultra-faint dwarf galaxy accreted either alone, as one of the low-mass building blocks of the proto-Galaxy, or as a satellite of Gaia-Sausage-Enceladus. The combination of Gemini's large aperture with GHOST's high efficiency and broad spectral coverage makes this new spectrograph one of the leading instruments for near-field cosmology investigations.Comment: Submitted to MNRAS. 8 figures, 15page