A search for the first massive galaxy clusters

We have obtained deep, multi-band imaging observations around three of the most distant known quasars at redshifts z>6. Standard accretion theory predicts that the supermassive black holes present in these quasars were formed at a very early epoch. If a correlation between black hole mass and dark matter halo mass is present at these early times, then these rare supermassive black holes will be located inside the most massive dark matter halos. These are therefore ideal locations to search for the first clusters of galaxies. We use the Lyman-break technique to identify star-forming galaxies at high redshifts. Our observations show no overdensity of star-forming galaxies in the fields of these quasars. The lack of (dust-free) luminous starburst companions indicates that the quasars may be the only massive galaxies in their vicinity undergoing a period of intense activity.Comment: 6 pages, 2 figures, contributed paper to Proceedings of the Conference "Growing Black Holes" held in Garching, Germany, June 21-25, 2004, edited by A. Merloni, S. Nayakshin and R. Sunyaev, Springer-Verlag series of "ESO Astrophysics Symposia

Association Mapping of Insecticide Resistance in Wild Anopheles gambiae Populations: Major Variants Identified in a Low-Linkage Disequilbrium Genome

Background: Association studies are a promising way to uncover the genetic basis of complex traits in wild populations. Data on population stratification, linkage disequilibrium and distribution of variant effect-sizes for different trait-types are required to predict study success but are lacking for most taxa. We quantified and investigated the impacts of these key variables in a large-scale association study of a strongly selected trait of medical importance: pyrethroid resistance in the African malaria vector Anopheles gambiae. Methodology/Principal Findings: We genotyped <1500 resistance-phenotyped wild mosquitoes from Ghana and Cameroon using a 1536-SNP array enriched for candidate insecticide resistance gene SNPs. Three factors greatly impacted study power. (1) Population stratification, which was attributable to co-occurrence of molecular forms (M and S), and cryptic within-form stratification necessitating both a partitioned analysis and genomic control. (2) All SNPs of substantial effect (odds ratio, OR.2) were rare (minor allele frequency, MAF,0.05). (3) Linkage disequilibrium (LD) was very low throughout most of the genome. Nevertheless, locally high LD, consistent with a recent selective sweep, and uniformly high ORs in each subsample facilitated significant direct and indirect detection of the known insecticide target site mutation kdr L1014F (OR<6; P,1026), but with resistance level modified by local haplotypic background. Conclusion: Primarily as a result of very low LD in wild A. Gambiae, LD-based association mapping is challenging, but is feasible at least for major effect variants, especially where LD is enhanced by selective sweeps. Such variants will be of greatest importance for predictive diagnostic screening

Four quasars above redshift 6 discovered by the Canada-France High-z Quasar Survey

The Canada-France High-z Quasar Survey (CFHQS) is an optical survey designed to locate quasars during the epoch of reionization. In this paper we present the discovery of the first four CFHQS quasars at redshift greater than 6, including the most distant known quasar, CFHQS J2329-0301 at z=6.43. We describe the observational method used to identify the quasars and present optical, infrared, and millimeter photometry and optical and near-infrared spectroscopy. We investigate the dust properties of these quasars finding an unusual dust extinction curve for one quasar and a high far-infrared luminosity due to dust emission for another. The mean millimeter continuum flux for CFHQS quasars is substantially lower than that for SDSS quasars at the same redshift, likely due to a correlation with quasar UV luminosity. For two quasars with sufficiently high signal-to-noise optical spectra, we use the spectra to investigate the ionization state of hydrogen at z>5. For CFHQS J1509-1749 at z=6.12, we find significant evolution (beyond a simple extrapolation of lower redshift data) in the Gunn-Peterson optical depth at z>5.4. The line-of-sight to this quasar has one of the highest known optical depths at z~5.8. An analysis of the sizes of the highly-ionized near-zones in the spectra of two quasars at z=6.12 and z=6.43 suggest the IGM surrounding these quasars was substantially ionized before these quasars turned on. Together, these observations point towards an extended reionization process, but we caution that cosmic variance is still a major limitation in z>6 quasar observations.Comment: 15 pages, 9 figures, AJ, in press, minor changes to previous versio

Development of optimised tissue-equivalent materials for proton therapy

OBJECTIVE: In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy. APPROACH: A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence. MAIN RESULTS: Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8 % for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1-2 % for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1-2 % of the experimental RSP, confirming their suitability as clinical phantom materials. SIGNIFICANCE: We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry

Active Galactic Nuclei in Groups and Clusters of Galaxies: Detection and Host Morphology

The incidence and properties of Active Galactic Nuclei (AGN) in the field, groups, and clusters can provide new information about how these objects are triggered and fueled, similar to how these environments have been employed to study galaxy evolution. We have obtained new XMM-Newton observations of seven X-ray selected groups and poor clusters with 0.02 < z < 0.06 for comparison with previous samples that mostly included rich clusters and optically-selected groups. Our final sample has ten groups and six clusters in this low-redshift range (split at a velocity dispersion of $\sigma = 500$ km/s). We find that the X-ray selected AGN fraction increases from $f_A(L_X>10^{41}; M_R<M_R^*+1) = 0.047^{+0.023}_{-0.016}$ in clusters to $0.091^{+0.049}_{-0.034}$ for the groups (85% significance), or a factor of two, for AGN above an 0.3-8keV X-ray luminosity of $10^{41}$ erg/s hosted by galaxies more luminous than $M_R^*+1$. The trend is similar, although less significant, for a lower-luminosity host threshold of $M_R = -20$ mag. For many of the groups in the sample we have also identified AGN via standard emission-line diagnostics and find that these AGN are nearly disjoint from the X-ray selected AGN. Because there are substantial differences in the morphological mix of galaxies between groups and clusters, we have also measured the AGN fraction for early-type galaxies alone to determine if the differences are directly due to environment, or indirectly due to the change in the morphological mix. We find that the AGN fraction in early-type galaxies is also lower in clusters $f_{A,n>2.5}(L_X>10^{41}; M_R<M_R^*+1) = 0.048^{+0.028}_{-0.019}$ compared to $0.119^{+0.064}_{-0.044}$ for the groups (92% significance), a result consistent with the hypothesis that the change in AGN fraction is directly connected to environment.Comment: 18 pages, 9 figures; accepted by The Astrophysical Journal; for higher-resolution versions of some figures, see http://u.arizona.edu/~tjarnold/Arnold09

The biogeography of the caribou lungworm, Varestrongylus eleguneniensis (Nematoda:Protostrongylidae) across northern North America

Varestrongylus eleguneniensis (Nematoda; Protostrongylidae) is a recently described species of lungworm that infects caribou (Rangifer tarandus), muskoxen (Ovibos moschatus) and moose (Alces americanus) across northern North America. Herein we explore the geographic distribution of V. eleguneniensis through geographically extensive sampling and discuss the biogeography of this multi-host parasite. We analyzed fecal samples of three caribou subspecies (n = 1485), two muskox subspecies (n = 159), and two moose subspecies (n = 264) from across northern North America. Protostrongylid dorsal-spined larvae (DSL) were found in 23.8%, 73.6%, and 4.2% of these ungulates, respectively. A portion of recovered DSL were identified by genetic analyses of the ITS-2 region of the nuclear rDNA or the cytochrome oxidase c subunit I (COI) region of the mtDNA. We found V. eleguneniensis widely distributed among caribou and muskox populations across most of their geographic prange in North America but it was rare in moose. Parelaphostrongylus andersoni was present in caribou and moose and we provide new geographic records for this species. This study provides a substantial expansion of the knowledge defining the current distribution and biogeography of protostrongylid nematodes in northern ungulates. Insights about the host and geographic range of V. eleguneniensis can serve as a geographically extensive baseline for monitoring current distribution and in anticipating future biogeographic scenarios under a regime of accelerating climate and anthropogenic perturbation.[Display omitted]•Varestrongylus eleguneniensis is a lungworm whose primary host is the caribou.•The muscleworm, Parelaphostrongylus andersoni, co-infects caribou across its range.•We expand the knowledge on distribution of the caribou lungworm and the muscleworm.•Muskoxen sympatric with caribou are infected with the caribou lungworm.•We discuss the biogeography of V. eleguneniensis and Rangifer across North America

Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules

Evolution in the Disks and Bulges of Group Galaxies since z=0.4

We present quantitative morphology measurements of a sample of optically selected group galaxies at 0.3 < z < 0.55 using the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) and the GIM2D surface brightness--fitting software package. The group sample is derived from the Canadian Network for Observational Cosmology Field Redshift survey (CNOC2) and follow-up Magellan spectroscopy. We compare these measurements to a similarly selected group sample from the Millennium Galaxy Catalogue (MGC) at 0.05 < z < 0.12. We find that, at both epochs, the group and field fractional bulge luminosity (B/T) distributions differ significantly, with the dominant difference being a deficit of disk--dominated (B/T < 0.2) galaxies in the group samples. At fixed luminosity, z=0.4 groups have ~ 5.5 +/- 2 % fewer disk--dominated galaxies than the field, while by z=0.1 this difference has increased to ~ 19 +/- 6 %. Despite the morphological evolution we see no evidence that the group environment is actively perturbing or otherwise affecting the entire existing disk population. At both redshifts, the disks of group galaxies have similar scaling relations and show similar median asymmetries as the disks of field galaxies. We do find evidence that the fraction of highly asymmetric, bulge--dominated galaxies is 6 +/- 3 % higher in groups than in the field, suggesting there may be enhanced merging in group environments. We replicate our group samples at z=0.4 and z=0 using the semi-analytic galaxy catalogues of Bower et al (2006). This model accurately reproduces the B/T distributions of the group and field at z=0.1. However, the model does not reproduce our finding that the deficit of disks in groups has increased significantly since z=0.4.Comment: Accepted for publication in MNRAS. 20 pages, 17 figure

Phase II Open Label Study of Valproic Acid in Spinal Muscular Atrophy

UNLABELLED:Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p<or=0.001); however, significant improvement was almost entirely restricted to participants <5 years of age. Full length SMN levels were unchanged and Delta7SMN levels were significantly reduced for 2 of 3 treatment visits. In contrast, bone mineral density (p<or=0.0036) and maximum ulnar CMAP scores (p<or=0.0001) increased significantly. CONCLUSIONS:While VPA appears safe and well-tolerated in this initial pilot trial, these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials. This study highlights potential strengths and limitations of various candidate outcome measures and underscores the need for additional controlled clinical trials with VPA targeting more restricted cohorts of subjects. TRIAL REGISTRATION:ClinicalTrials.gov

SMA CARNI-VAL Trial Part I: Double-Blind, Randomized, Placebo-Controlled Trial of L-Carnitine and Valproic Acid in Spinal Muscular Atrophy

Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo.Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures.At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007).This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials.Clinicaltrials.gov NCT00227266