Sparse aperture masking interferometry survey of transitional discs: Search for substellar-mass companions and asymmetries in their parent discs

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Context. Transitional discs are a class of circumstellar discs around young stars with extensive clearing of dusty material within their inner regions on 10s of au scales. One of the primary candidates for this kind of clearing is the formation of planet(s) within the disc that then accrete or clear their immediate area as they migrate through the disc. Aims. The goal of this survey was to search for asymmetries in the brightness distribution around a selection of transitional disc targets. We then aimed to determine whether these asymmetries trace dynamically-induced structures in the disc or the gap-opening planets themselves. Methods. Our sample included eight transitional discs. Using the Keck/NIRC2 instrument we utilised the Sparse Aperture Masking (SAM) interferometry technique to search for asymmetries indicative of ongoing planet formation. We searched for close-in companions using both model fitting and interferometric image reconstruction techniques. Using simulated data, we derived diagnostics that helped us to distinguish between point sources and extended asymmetric disc emission. In addition, we investigated the degeneracy between the contrast and separation that appear for marginally resolved companions. Results. We found FP Tau to contain a previously unseen disc wall, and DM Tau, LkHα330, and TW Hya to contain an asymmetric signal indicative of point source-like emission. We placed upper limits on the contrast of a companion in RXJ1842.9-3532 and V2246 Oph. We ruled the asymmetry signal in RXJ1615.3-3255 and V2062 Oph to be false positives. In the cases where our data indicated a potential companion we computed estimates for the value of McM˙ c and found values in the range of 10−5 − 10−3M2 J yr−1 . Conclusions. We found significant asymmetries in four targets. Of these, three were consistent with companions. We resolved a previously unseen gap in the disc of FP Tau extending inwards from approximately 10 au.We acknowledge support from a STFC Rutherford Fellowship and Grant (ST/J004030/1, ST/K003445/1), Marie Sklodowska-Curie CIG grant (Ref. 618910), and Philip Leverhulme Prize (PLP-2013-110). We additionally acknowledge support from NASA KPDA grants (JPL-1452321, 1474717, 1485953, 1496788). The authors wish to recognise and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundatio

Sparse aperture masking interferometry survey of transitional discs. Search for substellar-mass companions and asymmetries in their parent discs

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Context. Transitional discs are a class of circumstellar discs around young stars with extensive clearing of dusty material within their inner regions on 10s of au scales. One of the primary candidates for this kind of clearing is the formation of planet(s) within the disc that then accrete or clear their immediate area as they migrate through the disc. Aims. The goal of this survey was to search for asymmetries in the brightness distribution around a selection of transitional disc targets. We then aimed to determine whether these asymmetries trace dynamically-induced structures in the disc or the gap-opening planets themselves. Methods. Our sample included eight transitional discs. Using the Keck/NIRC2 instrument we utilised the Sparse Aperture Masking (SAM) interferometry technique to search for asymmetries indicative of ongoing planet formation. We searched for close-in companions using both model fitting and interferometric image reconstruction techniques. Using simulated data, we derived diagnostics that helped us to distinguish between point sources and extended asymmetric disc emission. In addition, we investigated the degeneracy between the contrast and separation that appear for marginally resolved companions. Results. We found FP Tau to contain a previously unseen disc wall, and DM Tau, LkHα330, and TW Hya to contain an asymmetric signal indicative of point source-like emission. We placed upper limits on the contrast of a companion in RXJ 1842.9-3532 and V2246 Oph. We ruled the asymmetry signal in RXJ 1615.3-3255 and V2062 Oph to be false positives. In the cases where our data indicated a potential companion we computed estimates for the value of McṀc and found values in the range of 10−5−10−3 M2J yr−1. Conclusions. We found significant asymmetries in four targets. Of these, three were consistent with companions. We resolved a previously unseen gap in the disc of FP Tau extending inwards from approximately 10 au.We acknowledge support from a STFC Rutherford Fellowship and Grant (ST/J004030/1, ST/K003445/1), Marie Sklodowska-Curie CIG grant (Ref. 618910), and Philip Leverhulme Prize (PLP-2013-110). We additionally acknowledge support from NASA KPDA grants (JPL-1452321, 1474717, 1485953, 1496788). The authors wish to recognise and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation

A Sensitive Branched DNA HIV-1 Signal Amplification Viral Load Assay with Single Day Turnaround

Branched DNA (bDNA) is a signal amplification technology used in clinical and research laboratories to quantitatively detect nucleic acids. An overnight incubation is a significant drawback of highly sensitive bDNA assays. The VERSANT® HIV-1 RNA 3.0 Assay (bDNA) (“Versant Assay”) currently used in clinical laboratories was modified to allow shorter target incubation, enabling the viral load assay to be run in a single day. To dramatically reduce the target incubation from 16–18 h to 2.5 h, composition of only the “Lysis Diluent” solution was modified. Nucleic acid probes in the assay were unchanged. Performance of the modified assay (assay in development; not commercially available) was evaluated and compared to the Versant Assay. Dilution series replicates (>950 results) were used to demonstrate that analytical sensitivity, linearity, accuracy, and precision for the shorter modified assay are comparable to the Versant Assay. HIV RNA-positive clinical specimens (n = 135) showed no significant difference in quantification between the modified assay and the Versant Assay. Equivalent relative quantification of samples of eight genotypes was demonstrated for the two assays. Elevated levels of several potentially interfering endogenous substances had no effect on quantification or specificity of the modified assay. The modified assay with drastically improved turnaround time demonstrates the viability of signal-amplifying technology, such as bDNA, as an alternative to the PCR-based assays dominating viral load monitoring in clinical laboratories. Highly sensitive bDNA assays with a single day turnaround may be ideal for laboratories with especially stringent cost, contamination, or reliability requirements

Methylation of hMLH1 promoter correlates with the gene silencing with a region-specific manner in colorectal cancer

Microsatellite instability is present in over 80% of the hereditary non-polyposis colorectal carcinoma and about 15–20% of the sporadic cancer. Microsatellite instability is caused by the inactivation of the mismatch repair genes, such as primarily hMLH1, hMSH2. To study the mechanisms of the inactivation of mismatch repair genes in colorectal cancers, especially the region-specific methylation of hMLH1 promoter and its correlation with gene expression, we analysed microsatellite instability, expression and methylation of hMLH1 and loss of heterozygosity at hMLH1 locus in these samples. Microsatellite instability was present in 17 of 71 primary tumours of colorectal cancer, including 14 of 39 (36%) mucinous cancer and three of 32 (9%) non-mucinous cancer. Loss of hMLH1 and hMSH2 expression was detected in nine and three of 16 microsatellite instability tumours respectively. Methylation at CpG sites in a proximal region of hMLH1 promoter was detected in seven of nine tumours that showed no hMLH1 expression, while no methylation was present in normal mucosa and tumours which express hMLH1. However, methylation in the distal region was observed in all tissues including normal mucosa and hMLH1 expressing tumours. This observation indicates that methylation of hMLH1 promoter plays an important role in microsatellite instability with a region-specific manner in colorectal cancer. Loss of heterozygosity at hMLH1 locus was present in four of 17 cell lines and 16 of 54 tumours with normal hMLH1 status, while loss of heterozygosity was absent in all nine cell lines and nine tumours with abnormal hMLH1 status (mutation or loss of expression), showing loss of heterozygosity is not frequently involved in the inactivation of hMLH1 gene in sporadic colorectal cancer

Worms take to the slo lane: a perspective on the mode of action of emodepside

The cyclo-octapdepsipeptide anthelmintic emodepside exerts a profound paralysis on parasitic and free-living nematodes. The neuromuscular junction is a significant determinant of this effect. Pharmacological and electrophysiological analyses in the parasitic nematode Ascaris suum have resolved that emodepside elicits a hyperpolarisation of body wall muscle, which is dependent on extracellular calcium and the efflux of potassium ions. The molecular basis for emodepside’s action has been investigated in forward genetic screens in the free-living nematode Caenorhabditis elegans. Two screens for emodepside resistance, totalling 20,000 genomes, identified several mutants of slo-1, which encodes a calcium-activated potassium channel homologous to mammalian BK channels. Slo-1 null mutants are more than 1000-fold less sensitive to emodepside than wild-type C. elegans and tissue-specific expression studies show emodepside acts on SLO-1 in neurons regulating feeding and motility as well as acting on SLO-1 in body wall muscle. These genetic data, combined with physiological measurements in C. elegans and the earlier physiological analyses on A. suum, define a pivotal role for SLO-1 in the mode of action of emodepside. Additional signalling pathways have emerged as determinants of emodepside’s mode of action through biochemical and hypothesis-driven approaches. Mutant analyses of these pathways suggest a modulatory role for each of them in emodepside’s mode of action; however, they impart much more modest changes in the sensitivity to emodepside than mutations in slo-1. Taken together these studies identify SLO-1 as the major determinant of emodepside’s anthelmintic activity. Structural information on the BK channels has advanced significantly in the last 2 years. Therefore, we rationalise this possibility by suggesting a model that speculates on the nature of the emodepside pharmacophore within the calcium-activated potassium channels

Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding

Peroxisome proliferator activated receptors (PPARs δ, α and γ) are closely related transcription factors that exert distinct effects on fatty acid and glucose metabolism, cardiac disease, inflammatory response and other processes. Several groups developed PPAR subtype specific modulators to trigger desirable effects of particular PPARs without harmful side effects associated with activation of other subtypes. Presently, however, many compounds that bind to one of the PPARs cross-react with others and rational strategies to obtain highly selective PPAR modulators are far from clear. GW0742 is a synthetic ligand that binds PPARδ more than 300-fold more tightly than PPARα or PPARγ but the structural basis of PPARδ:GW0742 interactions and reasons for strong selectivity are not clear. Here we report the crystal structure of the PPARδ:GW0742 complex. Comparisons of the PPARδ:GW0742 complex with published structures of PPARs in complex with α and γ selective agonists and pan agonists suggests that two residues (Val312 and Ile328) in the buried hormone binding pocket play special roles in PPARδ selective binding and experimental and computational analysis of effects of mutations in these residues confirms this and suggests that bulky substituents that line the PPARα and γ ligand binding pockets as structural barriers for GW0742 binding. This analysis suggests general strategies for selective PPARδ ligand design

Egg Production in a Coastal Seabird, the Glaucous-Winged Gull (Larus glaucescens), Declines during the Last Century

Seabirds integrate information about oceanic ecosystems across time and space, and are considered sensitive indicators of marine conditions. To assess whether hypothesized long-term foodweb changes such as forage fish declines may be reflected in a consumer's life history traits over time, I used meta-regression to evaluate multi-decadal changes in aspects of egg production in the glaucous-winged gull (Larus glaucescens), a common coastal bird. Study data were derived from literature searches of published papers and unpublished historical accounts, museum egg collections, and modern field studies, with inclusion criteria based on data quality and geographic area of the original study. Combined historical and modern data showed that gull egg size declined at an average of 0.04 cc y−1 from 1902 (108 y), equivalent to a decline of 5% of mean egg volume, while clutch size decreased over 48 y from a mean of 2.82 eggs per clutch in 1962 to 2.25 in 2009. There was a negative relationship between lay date and mean clutch size in a given year, with smaller clutches occurring in years where egg laying commenced later. Lay date itself advanced over time, with commencement of laying presently (2008–2010) 7 d later than in previous studies (1959–1986). This study demonstrates that glaucous-winged gull investment in egg production has declined significantly over the past ∼50–100 y, with such changes potentially contributing to recent population declines. Though gulls are generalist feeders that should readily be able to buffer themselves against food web changes, they are likely nutritionally constrained during the early breeding period, when egg production requirements are ideally met by consumption of high-quality prey such as forage fish. This study's results suggest a possible decline in the availability of such prey, and the incremental long-term impoverishment of a coastal marine ecosystem bordering one of North America's rapidly growing urban areas

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

Elevational Gradients in Bird Diversity in the Eastern Himalaya: An Evaluation of Distribution Patterns and Their Underlying Mechanisms

BACKGROUND: Understanding diversity patterns and the mechanisms underlying those patterns along elevational gradients is critically important for conservation efforts in montane ecosystems, especially those that are biodiversity hotspots. Despite recent advances, consensus on the underlying causes, or even the relative influence of a suite of factors on elevational diversity patterns has remained elusive. METHODS AND PRINCIPAL FINDINGS: We examined patterns of species richness, density and range size distribution of birds, and the suite of biotic and abiotic factors (primary productivity, habitat variables, climatic factors and geometric constraints) that governs diversity along a 4500-m elevational gradient in the Eastern Himalayan region, a biodiversity hotspot within the world's tallest mountains. We used point count methods for sampling birds and quadrats for estimating vegetation at 22 sites along the elevational gradient. We found that species richness increased to approximately 2000 m, then declined. We found no evidence that geometric constraints influenced this pattern, whereas actual evapotranspiration (a surrogate for primary productivity) and various habitat variables (plant species richness, shrub density and basal area of trees) accounted for most of the variation in bird species richness. We also observed that ranges of most bird species were narrow along the elevation gradient. We find little evidence to support Rapoport's rule for the birds of Sikkim region of the Himalaya. CONCLUSIONS AND SIGNIFICANCE: This study in the Eastern Himalaya indicates that species richness of birds is highest at intermediate elevations along one of the most extensive elevational gradients ever examined. Additionally, primary productivity and factors associated with habitat accounted for most of the variation in avian species richness. The diversity peak at intermediate elevations and the narrow elevational ranges of most species suggest important conservation implications: not only should mid-elevation areas be conserved, but the entire gradient requires equal conservation attention