Proto-clusters in the Lambda CDM Universe

We compare the highly clustered populations of very high redshift galaxies with proto-clusters identified numerically in a standard $\Lambda$CDM universe ($\Omega_0=0.3, \lambda_0=0.7$) simulation. We evolve 256^3 dark matter particles in a comoving box of side 150h^{-1}Mpc. By the present day there are 63 cluster sized objects of mass in excess of 10^{14}h^{-1}Mo in this box. We trace these clusters back to higher redshift finding that their progenitors at z=4--5 are extended regions of typically 20--40 Mpc (comoving) in size, with dark halos of mass in excess of 10^{12}h^{-1}Mo and are overdense by typically 1.3--13 times the cosmological mean density. Comparison with the observation of Lyman alpha emitting (LAEs) galaxies at z=4.86 and at z=4.1 indicates that the observed excess clustering is consistent with that expected for a proto-cluster region if LAEs typically correspond to massive dark halos of more than 10^{12}h^{-1}Mo. We give a brief discussion on the relation between high redshift concentration of massive dark halos and present day rich clusters of galaxies.Comment: 4 pages, 5 figures, Accepted for publication in ApJ Letter

Structure based development of novel specific inhibitors for cathepsin L and cathepsin S in vitro and in vivo

AbstractSpecific inhibitors for cathepsin L and cathepsin S have been developed with the help of computer-graphic modeling based on the stereo-structure. The common fragment, N-(L-trans-carbamoyloxyrane-2-carbonyl)-phenylalanine-dimethylamide, is required for specific inhibition of cathepsin L. Seven novel inhibitors of the cathepsin L inhibitor Katunuma (CLIK) specifically inhibited cathepsin L at a concentration of 10−7 M in vitro, while almost no inhibition of cathepsins B, C, S and K was observed. Four of the CLIKs are stable, and showed highly selective inhibition for hepatic cathepsin L in vivo. One of the CLIK inhibitors contains an aldehyde group, and specifically inhibits cathepsin S at 10−7 M in vitro

Dust Destruction in the High-Velocity Shocks Driven by Supernovae in the Early Universe

We investigate the destruction of dust grains by sputtering in the high-velocity interstellar shocks driven by supernovae (SNe) in the early universe to reveal the dependence of the time-scale of dust destruction on the gas density $n_{{\rm H}, 0}$ in the interstellar medium (ISM) as well as on the progenitor mass $M_{\rm pr}$ and explosion energy $E_{\rm 51}$ of SN. The sputtering yields for the combinations of dust and ion species of interest to us are evaluated by applying the so-called universal relation with a slight modification. The dynamics of dust grains and their destruction by sputtering in shock are calculated by taking into account the size distribution of each dust species, together with the time evolution of temperature and density of gas in spherically symmetric shocks. The results of calculations show that the efficiency of dust destruction depends not only on the sputtering yield but also on the initial size distribution of each grain species. The efficiency of dust destruction increases with increasing $E_{\rm 51}$ and/or increasing $n_{{\rm H}, 0}$, but is almost independent of $M_{\rm pr}$ as long as $E_{\rm 51}$ is the same. The mass of gas swept up by shock is the increasing function of $E_{\rm 51}$ and the decreasing function of $n_{{\rm H}, 0}$. Combining these results, we present the approximation formula for the time-scale of destruction for each grain species in the early universe as a function of $E_{\rm 51}$ and $n_{{\rm H}, 0}$. This formula is applicable for investigating the evolution of dust grains at the early epoch of the universe with the metallicity of Z \la 10^{-3} $Z_\odot$. The effects of the cooling processes of gas on the destruction of dust are briefly discussed.Comment: 49 pages including 7 tables and 25 figures, accepted for publication in Ap

The amphioxus genome and the evolution of the chordate karyotype

Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approx520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution

Clinical efficacy and safety of monthly oral ibandronate 100 mg versus monthly intravenous ibandronate 1 mg in Japanese patients with primary osteoporosis

Summary: The MOVEST study evaluated the efficacy and safety of monthly oral ibandronate versus licensed monthly IV ibandronate in Japanese osteoporotic patients. Relative BMD gains after 12 months were 5.22 % oral and 5.34 % IV, showing non-inferiority of oral to IV ibandronate (primary endpoint). No new safety concerns were identified. Introduction: The randomized, phase 3, double-blind MOVEST (Monthly Oral VErsus intravenouS ibandronaTe) study evaluated the efficacy and safety of monthly oral ibandronate versus the licensed monthly intravenous (IV) ibandronate regimen in Japanese patients with osteoporosis. Methods: Ambulatory patients aged ?55 years with primary osteoporosis were randomized to receive oral ibandronate 100 mg/month plus monthly IV placebo, or IV ibandronate 1 mg/month plus monthly oral placebo. The primary endpoint was non-inferiority of oral versus IV ibandronate with respect to bone mineral density (BMD) gains at the lumbar spine after 12 months of treatment. Results: Four hundred twenty-two patients were enrolled with 372 patients in the per-protocol set (183 and 189 in the oral and IV ibandronate groups, respectively). The relative change from baseline in lumbar spine BMD values for the oral and IV ibandronate groups, respectively, was 5.22 % (95 % confidence interval [CI] 4.65, 5.80) and 5.34 % (95 % CI 4.78, 5.90). The least squares mean difference between the two groups was ?0.23 % (95 % CI ?0.97, 0.51), showing non-inferiority of oral ibandronate to IV ibandronate (non-inferiority limit = ?1.60). Changes in BMD values at other sites, and bone turnover marker levels in the oral ibandronate group, were comparable with those of the IV group. The safety profile was similar to that previously demonstrated; no new safety concerns were identified. Conclusions: This study demonstrated the non-inferiority of oral ibandronate 100 mg/month to IV ibandronate 1 mg/month (licensed dose in Japan) in increasing lumbar spine BMD in Japanese patients with primary osteoporosis

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution