No abstract

No abstract

Autoimmune polyglandular syndrome type I (APS 1, also called APECED) is an autosomal-recessive disorder that maps to human chromosome 21q22.3 between markers D21S49 and D21S171 by linkage studies. We have isolated a novel gene from this region, AIRE (autoimmune regulator), which encodes a protein containing motifs suggestive of a transcription factor including two zinc-finger (PHD-finger) motifs, a proline-rich region and three LXXLL motifs. Two mutations, a C-->T substitution that changes the Arg 257 (CGA) to a stop codon (TGA) and an A-->G substitution that changes the Lys 83 (AAG) to a Glu codon (GAG), were found in this novel gene in Swiss and Finnish APECED patients. The Arg257stop (R257X) is the predominant mutation in Finnish APECED patients, accounting for 10/12 alleles studied. These results indicate that this gene is responsible for the pathogenesis of APECED. The identification of the gene defective in APECED should facilitate the genetic diagnosis and potential treatment of the disease and further enhance our general understanding of the mechanisms underlying autoimmune diseases.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Combing the three‐dimensional radiative transfer (RT) calculation and cosmological smoothed particle hydrodynamics (SPH) simulations, we study the escape fraction of ionizing photons (fesc) of high‐redshift galaxies at z= 3–6. Our simulations cover the halo mass range of Mh= 109–1012 M⊙. We post‐process several hundred simulated galaxies with the Authentic Radiative Transfer (art) code to study the halo mass dependence of fesc. In this paper, we restrict ourselves to the transfer of stellar radiation from local stellar population in each dark matter halo. We find that the average fesc steeply decreases as the halo mass increases, with a large scatter for the lower‐mass haloes. The low‐mass haloes with Mh∼ 109 M⊙ have large values of fesc (with an average of ∼0.4), whereas the massive haloes with Mh∼ 1011 M⊙ show small values of fesc (with an average of ∼0.07). This is because in our simulations, the massive haloes show more clumpy structure in gas distribution, and the star‐forming regions are embedded inside these clumps, making it more difficult for the ionizing photons to escape. On the other hand, in low‐mass haloes, there are often conical regions of highly ionized gas due to the shifted location of young star clusters from the centre of dark matter halo, which allows the ionizing photons to escape more easily than in the high‐mass haloes. By counting the number of escaped ionizing photons, we show that the star‐forming galaxies can ionize the intergalactic medium at z= 3–6. The main contributor to the ionizing photons is the haloes with Mh≲ 1010 M⊙ owing to their high fesc. The large dispersion in fesc suggests that there may be various sizes of H ii bubbles around the haloes even with the same mass in the early stages of reionization. We also examine the effect of UV background radiation field on fesc using simple, four different treatments of UV background.

No abstract

We compare two cosmological hydrodynamic simulation codes in the context of hierarchical galaxy formation: the Lagrangian smoothed particle hydrodynamics (SPH) code 'GADGET', and the Eulerian adaptive mesh refinement (AMR) code 'Enzo'. Both codes represent dark matter with the N-body method but use different gravity solvers and fundamentally different approaches for baryonic hydrodynamics. The SPH method in GADGET uses a recently developed 'entropy conserving' formulation of SPH, while for the mesh-based Enzo two different formulations of Eulerian hydrodynamics are employed: the piecewise parabolic method (PPM) extended with a dual energy formulation for cosmology, and the artificial viscosity-based scheme used in the magnetohydrodynamics code ZEUS. In this paper we focus on a comparison of cosmological simulations that follow either only dark matter, or also a non-radiative ('adiabatic') hydrodynamic gaseous component. We perform multiple simulations using both codes with varying spatial and mass resolution with identical initial conditions.The dark matter-only runs agree generally quite well provided Enzo is run with a comparatively fine root grid and a low overdensity threshold for mesh refinement, otherwise the abundance of low-mass halos is suppressed. This can be readily understood as a consequence of the hierarchical particle-mesh algorithm used by Enzo to compute gravitational forces, which tends to deliver lower force resolution than the tree-algorithm of GADGET at early times before any adaptive mesh refinement takes place. At comparable force resolution we find that the latter offers substantially better performance and lower memory consumption than the present gravity solver in Enzo. In simulations that include adiabatic gas dynamics we find general agreement in the distribution functions of temperature, entropy, and density for gas of moderate to high overdensity, as found inside dark matter halos. However, there are also some significant differences in the same quantities for gas of lower overdensity. For example, at z = 3 the fraction of cosmic gas that has temperature log T > 0.5 is ∼ 80% for both Enzo/ZEUS and GADGET, while it is 40 − 60% for Enzo/PPM. We argue that these discrepancies are due to differences in the shock-capturing abilities of the different methods. In particular, we find that the ZEUS implementation of artificial viscosity in Enzo leads to some unphysical heating at early times in preshock regions. While this is apparently a significantly weaker effect in GADGET, its use of an artificial viscosity technique may also make it prone to some excess generation of entropy which should be absent in ENZO/PPM. Overall, the hydrodynamical results for GADGET are bracketed by those for Enzo/ZEUS and Enzo/PPM, but are closer to Enzo/ZEUS.

Taking three independent approaches, we investigate the simultaneous constraints set on the cosmic star formation history from various observations, including stellar mass density and extragalactic background light (EBL). We compare results based on: 1) direct observations of past light-cone, 2) a model using local fossil evidence constrained by SDSS observations at z ∼ 0 (the 'Fossil' model), and 3) theoretical ab initio models from three calculations of cosmic star formation history: (a) new (1024) 3 Total Variation Diminishing (TVD) cosmological hydrodynamic simulation, (b) analytic expression of Hernquist & Springel based on cosmological Smoothed Particle Hydrodynamics (SPH) simulations, and (c) semi-analytic model of Cole et al.We find good agreement among the three independent approaches up to the order of observational errors, except that all the models predict bolometric EBL of I tot ≃ 37 − 52 nW m −2 sr −1 , which is at the lower edge of the the observational estimate by Hauser & Dwek (2001). We emphasize that the Fossil model that consists of two componentsspheroids and disks -, when normalized to the local observations, provides a surprisingly simple but accurate description of the cosmic star formation history and other observable quantities. Our analysis suggests that the consensus global parameters at z = 0 are: Ω ⋆ = 0.0023 ± 0.0004, I EBL = 43 ± 7 nW m −2 sr −1 , ρ ⋆ = (1.06 ± 0.22) × 10 −2 M ⊙ yr −1 Mpc −3 , j bol = (3.1 ± 0.2) × 10 8 L ⊙ Mpc −3 .