Efficient derivation of microglia-like cells from human pluripotent stem cells

Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions. These in vitro pluripotent stem cell-derived microglia-like cells (termed pMGLs) faithfully recapitulate the expected ontogeny and characteristics of their in vivo counterparts, and they resemble primary fetal human and mouse microglia. We generated these cells from multiple disease-specific cell lines and find that pMGLs derived from an hES model of Rett syndrome are smaller than their isogenic controls. We further describe a platform to study the integration and live behavior of pMGLs in organotypic 3D cultures. This modular differentiation system allows for the study of microglia in highly defined conditions as they mature in response to developmentally relevant cues, and it provides a framework in which to study the long-term interactions of microglia residing in a tissue-like environment.Simons Foundation (Grant SFARI 204106)National Institutes of Health (U.S.) (Grant HD 045022)National Institutes of Health (U.S.) (Grant R37-CA084198)National Institutes of Health (U.S.) (Grant NS088538)National Institutes of Health (U.S.) (Grant 1RF1 AG042978

Baryon Acoustic Oscillations in the Ly{\alpha} forest of BOSS DR11 quasars

We report a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly{\alpha} forest of high-redshift quasars with a statistical significance of five standard deviations. The study uses 137,562 quasars in the redshift range $2.1\le z \le 3.5$ from the Data Release 11 (DR11) of the Baryon Oscillation Spectroscopic Survey (BOSS) of SDSS-III. This sample contains three times the number of quasars used in previous studies. The measured position of the BAO peak determines the angular distance, $D_A(z=2.34)$ and expansion rate, $H(z=2.34)$, both on a scale set by the sound horizon at the drag epoch, $r_d$. We find $D_A/r_d=11.28\pm0.65(1\sigma)^{+2.8}_{-1.2}(2\sigma)$ and $D_H/r_d=9.18\pm0.28(1\sigma)\pm0.6(2\sigma)$ where $D_H=c/H$. The optimal combination, $\sim D_H^{0.7}D_A^{0.3}/r_d$ is determined with a precision of $\sim2\%$. For the value $r_d=147.4~{\rm Mpc}$, consistent with the CMB power spectrum measured by Planck, we find $D_A(z=2.34)=1662\pm96(1\sigma)~{\rm Mpc}$ and $H(z=2.34)=222\pm7(1\sigma)~{\rm km\,s^{-1}Mpc^{-1}}$. Tests with mock catalogs and variations of our analysis procedure have revealed no systematic uncertainties comparable to our statistical errors. Our results agree with the previously reported BAO measurement at the same redshift using the quasar-Ly{\alpha} forest cross-correlation. The auto-correlation and cross-correlation approaches are complementary because of the quite different impact of redshift-space distortion on the two measurements. The combined constraints from the two correlation functions imply values of $D_A/r_d$ and $D_H/r_d$ that are, respectively, 7% low and 7% high compared to the predictions of a flat $\Lambda$CDM cosmological model with the best-fit Planck parameters. With our estimated statistical errors, the significance of this discrepancy is $\approx 2.5\sigma$.Comment: Accepted for publication in A&A. 17 pages, 18 figure

Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

<p>Abstract</p> <p>Objective</p> <p>To expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA).</p> <p>Case report</p> <p>Two brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of blood peroxisomal markers strongly suggested a peroxisomal biogenesis disorder. Sequencing of candidate <it>PEX </it>genes revealed a homozygous c.865_866insA mutation in the <it>PEX2 </it>gene leading to a frameshift 17 codons upstream of the stop codon. <it>PEX </it>gene mutations usually result in a severe neurological phenotype (Zellweger spectrum disorders).</p> <p>Conclusions</p> <p>Genetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA.</p

The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations in the distribution of Ly-alpha absorption from the spectra of a sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter distance at z\approx2.5, BOSS will provide the first direct measurement of the expansion rate of the Universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars over 2.2 < z < 3.5, where their colors overlap those of stars. During the first year of the BOSS survey, quasar target selection methods were developed and tested to meet the requirement of delivering at least 15 quasars deg^-2 in this redshift range, out of 40 targets deg^-2. To achieve these surface densities, the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85. While detection of the BAO signature in the Ly-alpha absorption in quasar spectra does not require a uniform target selection, many other astrophysical studies do. We therefore defined a uniformly-selected subsample of 20 targets deg^-2, for which the selection efficiency is just over 50%. This "CORE" subsample will be fixed for Years Two through Five of the survey. In this paper we describe the evolution and implementation of the BOSS quasar target selection algorithms during the first two years of BOSS operations. We analyze the spectra obtained during the first year. 11,263 new z>2.2 quasars were spectroscopically confirmed by BOSS. Our current algorithms select an average of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS imaging. Multi-epoch optical data and data at other wavelengths can further improve the efficiency and completeness of BOSS quasar target selection. [Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars. Submitted to Ap

Approach for Predicting Production Scenarios Focused on Cross Impact Analysis

AbstractOne of the most consistent challenges in business is anticipating what the future holds and what impact it may have on current production systems. The scenario technique is a well-established method for developing and forecasting multiple future development paths for companies. However, this method is mostly employed to develop and to support strategic long-term decisions. The core idea of the approach introduced in this paper is to convey the future impact of today's decisions on production systems to employees involved in production planning processes. With the help of immersive visualization, performed in virtual reality (VR) systems, planning participants can perceive how the factory must adapt to fit future demands.In this paper, the focus is on the fourth phase of the scenario technique – so called scenario development – and, in particular, the cross impact analysis. With this methodology, the interrelations, or cross impacts of the different basic elements are determined. The cross impact analysis results serve as a basis for the development of a standardized tool that can be used to create probable production scenarios out of given production systems. This standardized tool will facilitate the usage of the scenario technique for factory planning projects, as it focuses the immense diversity of future uncertainties companies are faced with on the factory level

The Baryon Oscillation Spectroscopic Survey of SDSS-III

The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large scale structure. BOSS uses 1.5 million luminous galaxies as faint as i=19.9 over 10,000 square degrees to measure BAO to redshifts z<0.7. Observations of neutral hydrogen in the Lyman alpha forest in more than 150,000 quasar spectra (g<22) will constrain BAO over the redshift range 2.15<z<3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Lyman alpha forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance D_A to an accuracy of 1.0% at redshifts z=0.3 and z=0.57 and measurements of H(z) to 1.8% and 1.7% at the same redshifts. Forecasts for Lyman alpha forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate D_A(z) and H^{-1}(z) parameters to an accuracy of 1.9% at z~2.5 when the survey is complete. Here, we provide an overview of the selection of spectroscopic targets, planning of observations, and analysis of data and data quality of BOSS.Comment: 49 pages, 16 figures, accepted by A

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version