Robustness to systematics for future dark energy probes

We extend the Figure of Merit formalism usually adopted to quantify the statistical performance of future dark energy probes to assess the robustness of a future mission to plausible systematic bias. We introduce a new robustness Figure of Merit which can be computed in the Fisher Matrix formalism given arbitrary systematic biases in the observable quantities. We argue that robustness to systematics is an important new quantity that should be taken into account when optimizing future surveys. We illustrate our formalism with toy examples, and apply it to future type Ia supernova (SNIa) and baryonic acoustic oscillation (BAO) surveys. For the simplified systematic biases that we consider, we find that SNIa are a somewhat more robust probe of dark energy parameters than the BAO. We trace this back to a geometrical alignement of systematic bias direction with statistical degeneracy directions in the dark energy parameter space.Comment: Added clarifications following referee report, main results unchanged. Matched version accepted by MNRA

GREAT3 results I: systematic errors in shear estimation and the impact of real galaxy morphology

We present first results from the third GRavitational lEnsing Accuracy Testing (GREAT3) challenge, the third in a sequence of challenges for testing methods of inferring weak gravitational lensing shear distortions from simulated galaxy images. GREAT3 was divided into experiments to test three specific questions, and included simulated space- and ground-based data with constant or cosmologically-varying shear fields. The simplest (control) experiment included parametric galaxies with a realistic distribution of signal-to-noise, size, and ellipticity, and a complex point spread function (PSF). The other experiments tested the additional impact of realistic galaxy morphology, multiple exposure imaging, and the uncertainty about a spatially-varying PSF; the last two questions will be explored in Paper II. The 24 participating teams competed to estimate lensing shears to within systematic error tolerances for upcoming Stage-IV dark energy surveys, making 1525 submissions overall. GREAT3 saw considerable variety and innovation in the types of methods applied. Several teams now meet or exceed the targets in many of the tests conducted (to within the statistical errors). We conclude that the presence of realistic galaxy morphology in simulations changes shear calibration biases by $\sim 1$ per cent for a wide range of methods. Other effects such as truncation biases due to finite galaxy postage stamps, and the impact of galaxy type as measured by the S\'{e}rsic index, are quantified for the first time. Our results generalize previous studies regarding sensitivities to galaxy size and signal-to-noise, and to PSF properties such as seeing and defocus. Almost all methods' results support the simple model in which additive shear biases depend linearly on PSF ellipticity.Comment: 32 pages + 15 pages of technical appendices; 28 figures; submitted to MNRAS; latest version has minor updates in presentation of 4 figures, no changes in content or conclusion

GREAT3 results - I. Systematic errors in shear estimation and the impact of real galaxy morphology

We present first results from the third GRavitational lEnsing Accuracy Testing (GREAT3) challenge, the third in a sequence of challenges for testing methods of inferring weak gravitational lensing shear distortions from simulated galaxy images. GREAT3 was divided into experiments to test three specific questions, and included simulated space- and ground-based data with constant or cosmologically varying shear fields. The simplest (control) experiment included parametric galaxies with a realistic distribution of signal-to-noise, size, and ellipticity, and a complex point spread function (PSF). The other experiments tested the additional impact of realistic galaxy morphology, multiple exposure imaging, and the uncertainty about a spatially varying PSF; the last two questions will be explored in Paper II. The 24 participating teams competed to estimate lensing shears to within systematic error tolerances for upcoming Stage-IV dark energy surveys, making 1525 submissions overall. GREAT3 saw considerable variety and innovation in the types of methods applied. Several teams now meet or exceed the targets in many of the tests conducted (to within the statistical errors). We conclude that the presence of realistic galaxy morphology in simulations changes shear calibration biases by ∼1percent for a wide range of methods. Other effects such as truncation biases due to finite galaxy postage stamps, and the impact of galaxy type as measured by the Sérsic index, are quantified for the first time. Our results generalize previous studies regarding sensitivities to galaxy size and signal-to-noise, and to PSF properties such as seeing and defocus. Almost all methods' results support the simple model in which additive shear biases depend linearly on PSF ellipticit

The Phoenix stream : a cold stream in the southern hemisphere

We report the discovery of a stellar stream in the Dark Energy Survey Year 1 (Y1A1) data. The discovery was made through simple color–magnitude filters and visual inspection of the Y1A1 data. We refer to this new object as the Phoenix stream, after its resident constellation. After subtraction of the background stellar population we detect a clear signal of a simple stellar population. By fitting the ridge line of the stream in color–magnitude space, we find that a stellar population with age τ=11.5±0.5 Gyr and [Fe/H]<−1.6, located 17.5±0.9 kpc from the Sun, gives an adequate description of the stream stellar population. The stream is detected over an extension of 8°.1 (2.5 kpc) and has a width of ∼54 pc assuming a Gaussian profile, indicating that a globular cluster (GC) is a probable progenitor. There is no known GC within 5 kpc that is compatible with being the progenitor of the stream, assuming that the stream traces its orbit. We examined overdensities (ODs) along the stream, however, no obvious counterpart-bound stellar system is visible in the coadded images. We also find ODs along the stream that appear to be symmetrically distributed—consistent with the epicyclic OD scenario for the formation of cold streams—as well as a misalignment between the northern and southern part of stream. Despite the close proximity we find no evidence that this stream and the halo cluster NGC 1261 have a common accretion origin linked to the recently found EriPhe OD

Systemic and Local Hypoxia Synergize Through HIF1 to Compromise the Mitochondrial Metabolism of Alzheimer's Disease Microglia

Microglial cells are key contributors to Alzheimer’s disease (AD), constituting the first cellular line against Aß plaques. Local hypoxia and hypoperfusion, which are typically present in peripheral inflammatory foci, are also common in the AD brain. We describe here that Aß deposits are hypoxic and hypoperfused and that Aß plaque-associated microglia (AßAM) are characterized by the expression of hypoxia-inducible factor 1 (HIF1)-regulated genes. Notably, AßAM simultaneously upregulate the expression of genes involved in anaerobic glycolysis and oxidative mitochondrial metabolism, show elongated mitochondria surrounded by rough endoplasmic reticulum, and blunt the HIF1-mediated exclusion of pyruvate from the mitochondria through the pyruvate dehydrogenase kinase 1 (PDK1). Overstabilization of HIF1 –by genetic (von Hippel-Lindau deficient microglia) or systemic hypoxia (an AD risk factor)– induces PDK1 in microglia and reduces microglial clustering in AD mouse models. The human AD brain exhibits increased HIF1 activity and a hypoxic brain area shows reduced microglial clustering. The loss of the microglial barrier associates with augmented Aß neuropathology both in the chronic hypoxia AD mouse model and the human AD brain. Thus, the synergy between local and systemic AD risk factors converges with genetic susceptibility to cause microglial dysfunction.Peer reviewe

Searching for dark matter annihilation in recently discovered Milky Way satellites with Fermi-LAT

We search for excess γ-ray emission coincident with the positions of confirmed and candidate Milky Way satellite galaxies using six years of data from the Fermi Large Area Telescope (LAT). Our sample of 45 stellar systems includes 28 kinematically confirmed dark-matter-dominated dwarf spheroidal galaxies (dSphs) and 17 recently discovered systems that have photometric characteristics consistent with the population of known dSphs. For each of these targets, the relative predicted γ-ray flux due to dark matter annihilation is taken from kinematic analysis if available, and estimated from a distance-based scaling relation otherwise, assuming that the stellar systems are DM-dominated dSphs. LAT data coincident with four of the newly discovered targets show a slight preference (each ~2σ local) for γ-ray emission in excess of the background. However, the ensemble of derived γ-ray flux upper limits for individual targets is consistent with the expectation from analyzing random blank-sky regions, and a combined analysis of the population of stellar systems yields no globally significant excess (global significance 1 TeV and mDM,t+t-> 70 GeV) and weakening by a factor of ~1.5 at lower masses relative to previously observed limits

Redshift distributions of galaxies in the Dark Energy Survey Science Verification shear catalogue and implications for weak lensing

We present photometric redshift estimates for galaxies used in the weak lensing analysis of the Dark Energy Survey Science Verification (DES SV) data. Four model- or machine learning-based photometric redshift methods—ANNZ2, BPZ calibrated against BCC-Ufig simulations, SKYNET, and TPZ—are analyzed. For training, calibration, and testing of these methods, we construct a catalogue of spectroscopically confirmed galaxies matched against DES SV data. The performance of the methods is evaluated against the matched spectroscopic catalogue, focusing on metrics relevant for weak lensing analyses, with additional validation against COSMOS photo-z’s. From the galaxies in the DES SV shear catalogue, which have mean redshift 0.72 0.01 over the range 0.3 < z < 1.3, we construct three tomographic bins with means of z ¼ f0.45; 0.67; 1.00g. These bins each have systematic uncertainties δz ≲ 0.05 in the mean of the fiducial SKYNET photo-z nðzÞ. We propagate the errors in the redshift distributions through to their impact on cosmological parameters estimated with cosmic shear, and find that they cause shifts in the value of σ8 of approximately 3%. This shift is within the one sigma statistical errors on σ8 for the DES SV shear catalogue. We further study the potential impact of systematic differences on the critical surface density, Σcrit, finding levels of bias safely less than the statistical power of DES SV data. We recommend a final Gaussian prior for the photo-z bias in the mean of nðzÞ of width 0.05 for each of the three tomographic bins, and show that this is a sufficient bias model for the corresponding cosmology analysis

Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1

Genetic Alzheimer’s disease (AD) risk factors associate with reduced defensive amyloid β plaque-associated microglia (AβAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AβAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AβAM clustering and proliferation and increases Aβ neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aβ plaque microglial coverage and an increase of Aβ plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.R.M.-D. was the recipient of a Sara Borrell fellowship from Instituto de Salud Carlos III (ISCIII) (CD09/0007). N.L.-U., C.O.-d.S.L., C.R.-M. and M.I.A.-V. were the recipients of FPU fellowships from Spanish Ministry of Education, Culture and Sport (FPU14/02115, AP2010‐1598, FPU16/02050 and FPU15/02898, respectively). A.H.-G. was the recipient of an FPI fellowship from the Spanish Ministry of Education, Culture and Sport (BES-2010-033886). This work was supported by grants from the Spanish MINEICO, ISCIII and FEDER (European Union) (SAF2012‐33816, SAF2015‐64111‐R, SAF2017-90794-REDT and PIE13/0004 to A.P.); by the Regional Government of Andalusia co-funded by CEC and FEDER funds (European Union) (‘Proyectos de Excelencia’; P12‐CTS‐2138 and P12‐CTS‐2232 to A.P.); by the ‘Ayuda de Biomedicina 2018’, Fundación Domingo Martínez (to A.P.) ; by the ISCIII of Spain, co-financed by FEDER funds (European Union) through grants PI18/01556 (to J.V.) and PI18/01557 (to A. Gutierrez); by Junta de Andalucía, co-financed by FEDER funds (grants UMA18-FEDERJA-211 (to A. Gutierrez) and US‐1262734 (to J.V.)); and by Spanish MINEICO (BFU2016-76872-R and BES-2011-047721 to E.B.).Peer reviewe

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist