A high resolution, high frame rate detector based on a microchannel plate read out with the Medipix2 counting CMOS pixel chip.

The future of ground-based optical astronomy lies with advancements in adaptive optics (AO) to overcome the limitations that the atmosphere places on high resolution imaging. A key technology for AO systems on future very large telescopes are the wavefront sensors (WFS) which detect the optical phase error and send corrections to deformable mirrors. Telescopes with >30 m diameters will require WFS detectors that have large pixel formats (512x512), low noise (<3 e-/pixel) and very high frame rates (~1 kHz). These requirements have led to the idea of a bare CMOS active pixel device (the Medipix2 chip) functioning in counting mode as an anode with noiseless readout for a microchannel plate (MCP) detector and at 1 kHz continuous frame rate. First measurement results obtained with this novel detector are presented both for UV photons and beta particles

A noiseless kilohertz frame rate imaging detector based on microchannel plates read out with the Medipix2 CMOS pixel chip

A new hybrid optical imaging detector is described that is being developed for the next generation adaptive optics (AO) wavefront sensors (WFS) for ground-based telescopes. The detector consists of a photocathode and proximity focused microchannel plates (MCPs) read out by the Medipix2 CMOS pixel ASIC. Each pixel of the Medipix2 device measures 55x55 um2 and comprises pre-amplifier, a window discriminator and a 14-bit counter. The 256x256 Medipix2 array can be read out noiselessly in 287 us. The readout can be electronically shuttered down to a temporal window of a few us. The Medipix2 is buttable on 3 sides to produce 512x(n*256) pixel devices. Measurements with ultraviolet light yield a spatial resolution of the detector at the Nyquist limit. Sub-pixel resolution can be achieved using centroiding algorithms. For the AO application, very high continuous frame rates of the order of 1 kHz are required for a matrix of 512x512 pixels. The design concepts of a parallel readout board are presented that will allow this fast data throughput. The development status of the optical WFS tube is also explained

Moisture susceptibility of high and low compaction dry process crumb rubber modified asphalt mixtures

The field performance of dry process crumb rubber-modified (CRM) asphalt mixtures has been reported to be inconsistent with stripping and premature cracking on the surfacing. One of the concerns is that, because achieving field compaction of CRM material is difficult due to the inherent resilient nature of the rubber particle, nonuniform field compaction may lead to a deficient bond between rubber and bitumen. To assess the influence of compaction, a series of CRM and control mixtures was produced and compacted at two levels: 4% (low, optimum laboratory compaction) and 8% (high, field experience) air void content. The long-term durability, in regard to moisture susceptibility of the mixtures, was assessed by conducting repeated moisture conditioning cycles. Mechanical properties (stiffness, fatigue, and resistance to permanent deformation) were determined in the Nottingham Asphalt Tester. Results indicated that compared with conventional mixtures, the CRM mixtures, regardless of compaction effort, are more susceptible to moisture with the degree of susceptibility primarily depending on the amount of rubber in the mixture, rather than the difference in compaction. This behavior is different from that of conventional mixtures in which, as expected, poorly compacted mixtures were found to be more susceptible to moisture than were well-compacted mixtures

Examining the Impact of Imputation Errors on Fine-Mapping Using DNA Methylation QTL as a Model Trait

Genetic variants disrupting DNA methylation at CpG dinucleotides (CpG-SNP) provide a set of known causal variants to serve as models for testing fine-mapping methodology. We use 1716 CpG-SNPs to test three fine-mapping approaches (BIMBAM, BSLMM, and the J-test), assessing the impact of imputation errors and the choice of reference panel by using both whole-genome sequence (WGS), and genotype array data on the same individuals (n=1166). The choice of imputation reference panel had a strong effect on imputation accuracy, with the 1000 Genomes Phase 3 (1000G) reference panel (n=2504 from 26 populations) giving a mean non-reference discordance rate between imputed and sequenced genotypes of 3.2% compared to 1.6% when using the Haplotype Reference Consortium (HRC) reference panel (n=32470 Europeans). These imputation errors impacted on whether the CpG-SNP was included in the 95% credible set, with a difference of ∼ 23% and ∼ 7% between the WGS and the 1000G and HRC imputed datasets respectively. All of the fine-mapping methods failed to reach the expected 95% coverage of the CpG-SNP. This is attributed to secondary cis genetic effects that are unable to be statistically separated from the CpG-SNP, and through a masking mechanism where the effect of the methylation disrupting allele at the CpG-SNP is hidden by the effect of a nearby SNP that has strong LD with the CpG-SNP. The reduced accuracy in fine-mapping a known causal variant in a low level biological trait with imputed genetic data has implications for the study of higher order complex traits and disease

Neutral H density at the termination shock: a consolidation of recent results

We discuss a consolidation of determinations of the density of neutral interstellar H at the nose of the termination shock carried out with the use of various data sets, techniques, and modeling approaches. In particular, we focus on the determination of this density based on observations of H pickup ions on Ulysses during its aphelion passage through the ecliptic plane. We discuss in greater detail a novel method of determination of the density from these measurements and review the results from its application to actual data. The H density at TS derived from this analysis is equal to 0.087 \pm 0.022 cm-3, and when all relevant determinations are taken into account, the consolidated density is obtained at 0.09 \pm 0.022 cm-3. The density of H in CHISM based on literature values of filtration factor is then calculated at 0.16 \pm 0.04 cm-3.Comment: Submitted to Space Science Review

Is the Sun Embedded in a Typical Interstellar Cloud?

The physical properties and kinematics of the partially ionized interstellar material near the Sun are typical of warm diffuse clouds in the solar vicinity. The interstellar magnetic field at the heliosphere and the kinematics of nearby clouds are naturally explained in terms of the S1 superbubble shell. The interstellar radiation field at the Sun appears to be harder than the field ionizing ambient diffuse gas, which may be a consequence of the low opacity of the tiny cloud surrounding the heliosphere. The spatial context of the Local Bubble is consistent with our location in the Orion spur.Comment: "From the Outer Heliosphere to the Local Bubble", held at International Space Sciences Institute, October 200

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background: Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. / Methods: We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. / Findings: Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). / Interpretation: These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. / Funding: The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson's disease heritability

Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types

The Cosmic Origins Spectrograph

The Cosmic Origins Spectrograph (COS) is a moderate-resolution spectrograph with unprecedented sensitivity that was installed into the Hubble Space Telescope (HST) in May 2009, during HST Servicing Mission 4 (STS-125). We present the design philosophy and summarize the key characteristics of the instrument that will be of interest to potential observers. For faint targets, with flux F_lambda ~ 1.0E10-14 ergs/s/cm2/Angstrom, COS can achieve comparable signal to noise (when compared to STIS echelle modes) in 1-2% of the observing time. This has led to a significant increase in the total data volume and data quality available to the community. For example, in the first 20 months of science operation (September 2009 - June 2011) the cumulative redshift pathlength of extragalactic sight lines sampled by COS is 9 times that sampled at moderate resolution in 19 previous years of Hubble observations. COS programs have observed 214 distinct lines of sight suitable for study of the intergalactic medium as of June 2011. COS has measured, for the first time with high reliability, broad Lya absorbers and Ne VIII in the intergalactic medium, and observed the HeII reionization epoch along multiple sightlines. COS has detected the first CO emission and absorption in the UV spectra of low-mass circumstellar disks at the epoch of giant planet formation, and detected multiple ionization states of metals in extra-solar planetary atmospheres. In the coming years, COS will continue its census of intergalactic gas, probe galactic and cosmic structure, and explore physics in our solar system and Galaxy.Comment: 17 pages, 15 figure