Development of the X-ray camera for the OGRE sub-orbital rocket

Current theories regarding the matter composition of the universe suggest that half of the expected baryonic matter is missing. One region this could be residing in is intergalactic filaments which absorb strongly in the X-ray regime. Present space based technology is limited when it comes to imaging at these wavelengths and so new techniques are required. The Off-Plane Grating Rocket Experiment (OGRE) aims to produce the highest resolution spectrum of the binary star system Capella, a well-known X-ray source, in the soft X-ray range (0.2keV to 2keV). This will be achieved using a specialised payload combining three low technology readiness level components placed on-board a sub-orbital rocket. These three components consist of an array of large format off-plane X-ray diffraction gratings, a Wolter Type 1 mirror made using single crystal silicon, and the use of EM-CCDs to capture soft X-rays. Each of these components have been previously reviewed with OGRE being the first project to utilise them in a space observation mission. This paper focuses on the EM-CCDs (CCD207-40 by e2v) that will be used and their optimisation with a camera purposely designed for OGRE. Electron Multiplying gain curves were produced for the back-illuminated devices at -80 degrees Celsius. Further tests which will need to be carried out are discussed and the impact of the OGRE mission on future projects mentioned

Comparative Genomic Analyses of the Moraxella catarrhalis Serosensitive and Seroresistant Lineages Demonstrate Their Independent Evolution

Contains fulltext : 172169.pdf (publisher's version ) (Open Access)The bacterial speciesMoraxella catarrhalishas been hypothesized as being composed of two distinct lineages (referred to as the seroresistant [SR] and serosensitive [SS]) with separate evolutionary histories based on several molecular typing methods, whereas 16S ribotyping has suggested an additional split within the SS lineage. Previously, we characterized whole-genome sequences of 12 SR-lineage isolates, which revealed a relatively small supragenome when compared with other opportunistic nasopharyngeal pathogens, suggestive of a relatively short evolutionary history. Here, we performed whole-genome sequencing on 18 strains from both ribotypes of the SS lineage, an additional SR strain, as well as four previously identified highly divergent strains based on multilocus sequence typing analyses. All 35 strains were subjected to a battery of comparative genomic analyses which clearly show that there are three lineages-the SR, SS, and the divergent. The SR and SS lineages are closely related, but distinct from each other based on three different methods of comparison: Allelic differences observed among core genes; possession of lineage-specific sets of core and distributed genes; and by an alignment of concatenated core sequences irrespective of gene annotation. All these methods show that the SS lineage has much longer interstrain branches than the SR lineage indicating that this lineage has likely been evolving either longer or faster than the SR lineage. There is evidence of extensive horizontal gene transfer (HGT) within both of these lineages, and to a lesser degree between them. In particular, we identified very high rates of HGT between these two lineages for ss-lactamase genes. The four divergent strains aresui generis, being much more distantly related to both the SR and SS groups than these other two groups are to each other. Based on average nucleotide identities, gene content, GC content, and genome size, this group could be considered as a separate taxonomic group. The SR and SS lineages, although distinct, clearly form a single species based on multiple criteria including a large common core genome, average nucleotide identity values, GC content, and genome size. Although neither of these lineages arose from within the other based on phylogenetic analyses, the question of how and when these lineages split and then subsequently reunited in the human nasopharynx is explored

Precise Estimates of the Physical Parameters for the Exoplanet System HD-17156 Enabled by HST FGS Transit and Asteroseismic Observations

We present observations of three distinct transits of HD 17156b obtained with the Fine Guidance Sensors (FGS) on board the Hubble Space Telescope} (HST). We analyzed both the transit photometry and previously published radial velocities to find the planet-star radius ratio R_p/R_s = 0.07454 +/- 0.00035, inclination i=86.49 +0.24/-0.20 deg, and scaled semi-major axis a/R = 23.19 +0.32/-0.27. This last value translates directly to a mean stellar density determination of 0.522 +0.021/-0.018 g cm^-3. Analysis of asteroseismology observations by the companion paper of Gilliland et al. (2009) provides a consistent but significantly refined measurement of the stellar mean density. We compare stellar isochrones to this density estimate and find M_s = 1.275 +/- 0.018 M_sun and a stellar age of $3.37 +0.20/-0.47 Gyr. Using this estimate of M_s and incorporating the density constraint from asteroseismology, we model both the photometry and published radial velocities to estimate the planet radius R_p= 1.0870 +/- 0.0066 Jupiter radii and the stellar radius R_s = 1.5007 +/- 0.0076 R_sun. The planet radius is larger than that found in previous studies and consistent with theoretical models of a solar-composition gas giant of the same mass and equilibrium temperature. For the three transits, we determine the times of mid-transit to a precision of 6.2 s, 7.6 s, and 6.9 s, and the transit times for HD 17156 do not show any significant departures from a constant period. The joint analysis of transit photometry and asteroseismology presages similar studies that will be enabled by the NASA Kepler Mission.Comment: Accepted for publication to Ap

practice of mechanical ventilation in cardiac arrest patients and effects of targeted temperature management a substudy of the targeted temperature management trial

Aims: Mechanical ventilation practices in patients with cardiac arrest are not well described. Also, the effect of temperature on mechanical ventilation settings is not known. The aims of this study were 1) to describe practice of mechanical ventilation and its relation with outcome 2) to determine effects of different target temperatures strategies (33 °C versus 36 °C) on mechanical ventilation settings. Methods: This is a substudy of the TTM-trial in which unconscious survivors of a cardiac arrest due to a cardiac cause were randomized to two TTM strategies, 33 °C (TTM33) and 36 °C (TTM36). Mechanical ventilation data were obtained at three time points: 1) before TTM; 2) at the end of TTM (before rewarming) and 3) after rewarming. Logistic regression was used to determine an association between mechanical ventilation variables and outcome. Repeated-measures mixed modelling was performed to determine the effect of TTM on ventilation settings. Results: Mechanical ventilation data was available for 567 of the 950 TTM patients. Of these, 81% was male with a mean (SD) age of 64 (12) years. At the end of TTM median tidal volume was 7.7 ml/kg predicted body weight (PBW)(6.4–8.7) and 60% of patients were ventilated with a tidal volume ≤ 8 ml/kg PBW. Median PEEP was 7.7cmH2O (6.4–8.7) and mean driving pressure was 14.6 cmH2O (±4.3). The median FiO2 fraction was 0.35 (0.30–0.45). Multivariate analysis showed an independent relationship between increased respiratory rate and 28-day mortality. TTM33 resulted in lower end-tidal CO2 (Pgroup = 0.0003) and higher alveolar dead space fraction (Pgroup = 0.003) compared to TTM36, while PCO2 levels and respiratory minute volume were similar between groups. Conclusions: In the majority of the cardiac arrest patients, protective ventilation settings are applied, including low tidal volumes and driving pressures. High respiratory rate was associated with mortality. TTM33 results in lower end-tidal CO2 levels and a higher alveolar dead space fraction compared to TTTM36

Design and validation of a supragenome array for determination of the genomic content of Haemophilus influenzae isolates

Abstract Background Haemophilus influenzae colonizes the human nasopharynx as a commensal, and is etiologically associated with numerous opportunistic infections of the airway; it is also less commonly associated with invasive disease. Clinical isolates of H. influenzae display extensive genomic diversity and plasticity. The development of strategies to successfully prevent, diagnose and treat H. influenzae infections depends on tools to ascertain the gene content of individual isolates. Results We describe and validate a Haemophilus influenzae supragenome hybridization (SGH) array that can be used to characterize the full genic complement of any strain within the species, as well as strains from several highly related species. The array contains 31,307 probes that collectively cover essentially all alleles of the 2890 gene clusters identified from the whole genome sequencing of 24 clinical H. influenzae strains. The finite supragenome model predicts that these data include greater than 85% of all non-rare genes (where rare genes are defined as those present in less than 10% of sequenced strains). The veracity of the array was tested by comparing the whole genome sequences of eight strains with their hybridization data obtained using the supragenome array. The array predictions were correct and reproducible for ~ 98% of the gene content of all of the sequenced strains. This technology was then applied to an investigation of the gene content of 193 geographically and clinically diverse H. influenzae clinical strains. These strains came from multiple locations from five different continents and Papua New Guinea and include isolates from: the middle ears of persons with otitis media and otorrhea; lung aspirates and sputum samples from pneumonia and COPD patients, blood specimens from patients with sepsis; cerebrospinal fluid from patients with meningitis, as well as from pharyngeal specimens from healthy persons. Conclusions These analyses provided the most comprehensive and detailed genomic/phylogenetic look at this species to date, and identified a subset of highly divergent strains that form a separate lineage within the species. This array provides a cost-effective and high-throughput tool to determine the gene content of any H. influenzae isolate or lineage. Furthermore, the method for probe selection can be applied to any species, given a group of available whole genome sequences.http://deepblue.lib.umich.edu/bitstream/2027.42/112375/1/12864_2012_Article_5193.pd

Optical design of the Off-plane Grating Rocket Experiment

The Off-plane Grating Rocket Experiment (OGRE) is a soft X-ray spectroscopy suborbital rocket payload scheduled for launch in Q3 2020 from Wallops Flight Facility. The payload will serve as a testbed for several key technologies which can help achieve the desired performance increases for the next generation of X-ray spectrographs and other space-based missions: monocrystalline silicon X-ray mirrors developed at NASA Goddard Space Flight Center, reflection gratings manufactured at The Pennsylvania State University, and electron-multiplying CCDs developed by the Open University and XCAM Ltd. With these three technologies, OGRE hopes to obtain the highest-resolution on-sky soft X-ray spectrum to date. We discuss the optical design of the OGRE payload

The Off-plane Grating Rocket Experiment (OGRE) system overview

The Off-plane Grating Rocket Experiment (OGRE) is a sub-orbital rocket payload that will make the highest spectral resolution astronomical observation of the soft X-ray Universe to date. Capella, OGRE’s science target, has a well-defined line emission spectrum and is frequently used as a calibration source for X-ray observatories such as Chandra. This makes Capella an excellent target to test the technologies on OGRE, many of which have not previously flown. Through the use of state-of-the-art X-ray optics, co-aligned arrays of off-plane reflection gratings, and an X-ray camera based around four Electron Multiplying CCDs, OGRE will act as a proving ground for next generation X-ray spectrometers

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

<i>De Novo</i> and Rare Variants at Multiple Loci Support the Oligogenic Origins of Atrioventricular Septal Heart Defects

Congenital heart disease (CHD) has a complex genetic etiology, and recent studies suggest that high penetrance de novo mutations may account for only a small fraction of disease. In a multi-institutional cohort surveyed by exome sequencing, combining analysis of 987 individuals (discovery cohort of 59 affected trios and 59 control trios, and a replication cohort of 100 affected singletons and 533 unaffected singletons) we observe variation at novel and known loci related to a specific cardiac malformation the atrioventricular septal defect (AVSD). In a primary analysis, by combining developmental coexpression networks with inheritance modeling, we identify a de novo mutation in the DNA binding domain of NR1D2 (p.R175W). We show that p.R175W changes the transcriptional activity of Nr1d2 using an in vitro transactivation model in HUVEC cells. Finally, we demonstrate previously unrecognized cardiovascular malformations in the Nr1d2tm1-Dgen knockout mouse. In secondary analyses we map genetic variation to protein-interaction networks suggesting a role for two collagen genes in AVSD, which we corroborate by burden testing in a second replication cohort of 100 AVSDs and 533 controls (p = 8.37e-08). Finally, we apply a rare-disease inheritance model to identify variation in genes previously associated with CHD (ZFPM2, NSD1, NOTCH1, VCAN, and MYH6), cardiac malformations in mouse models (ADAM17, CHRD, IFT140, PTPRJ, RYR1 and ATE1), and hypomorphic alleles of genes causing syndromic CHD (EHMT1, SRCAP, BBS2, NOTCH2, and KMT2D) in 14 of 59 trios, greatly exceeding variation in control trios without CHD (p = 9.60e-06). In total, 32% of trios carried at least one putatively disease-associated variant across 19 loci,suggesting that inherited and de novo variation across a heterogeneous group of loci may contribute to disease risk