Executive Summary of Propulsion on the Orion Abort Flight-Test Vehicles

The National Aeronautics and Space Administration Orion Flight Test Office was tasked with conducting a series of flight tests in several launch abort scenarios to certify that the Orion Launch Abort System is capable of delivering astronauts aboard the Orion Crew Module to a safe environment, away from a failed booster. The first of this series was the Orion Pad Abort 1 Flight-Test Vehicle, which was successfully flown on May 6, 2010 at the White Sands Missile Range in New Mexico. This report provides a brief overview of the three propulsive subsystems used on the Pad Abort 1 Flight-Test Vehicle. An overview of the propulsive systems originally planned for future flight-test vehicles is also provided, which also includes the cold gas Reaction Control System within the Crew Module, and the Peacekeeper first stage rocket motor encased within the Abort Test Booster aeroshell. Although the Constellation program has been cancelled and the operational role of the Orion spacecraft has significantly evolved, lessons learned from Pad Abort 1 and the other flight-test vehicles could certainly contribute to the vehicle architecture of many future human-rated space launch vehicle

The Alliance for Cellular Signaling Plasmid Collection: A Flexible Resource for Protein Localization Studies and Signaling Pathway Analysis

Cellular responses to inputs that vary both temporally and spatially are determined by complex relationships between the components of cell signaling networks. Analysis of these relationships requires access to a wide range of experimental reagents and techniques, including the ability to express the protein components of the model cells in a variety of contexts. As part of the Alliance for Cellular Signaling, we developed a robust method for cloning large numbers of signaling ORFs into Gateway® entry vectors, and we created a wide range of compatible expression platforms for proteomics applications. To date, we have generated over 3000 plasmids that are available to the scientific community via the American Type Culture Collection. We have established a website at www.signaling-gateway.org/data/plasmid/ that allows users to browse, search, and blast Alliance for Cellular Signaling plasmids. The collection primarily contains murine signaling ORFs with an emphasis on kinases and G protein signaling genes. Here we describe the cloning, databasing, and application of this proteomics resource for large scale subcellular localization screens in mammalian cell lines

Molecular epidemiology of pneumococci obtained from Gambian children aged 2–29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine

BACKGROUND: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children METHODS: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2-29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. RESULTS: Twenty-nine different serotypes were identified; serotypes 14, 19A, 12F, 5, 23F, and 1 were common and accounted for 58.3% of all serotypes overall. MLST analysis showed 72 sequence types (STs) of which 46 are novel. eBURST analysis using the stringent 6/7 identical loci definition, grouped the isolates into 17 clonal complexes and 32 singletons. The population structure of the 8 serotype 1 isolates obtained from 4 vaccinated and 2 unvaccinated children were the same (ST 618) except that one (ST3336) of the isolates from an unvaccinated child had a novel ST which is a single locus variant of ST 618. CONCLUSION: We provide the first background data on the genetic structure of S. pneumoniae causing IPD prior to PC7V use in The Gambia. This data will be important for assessing the impact of PC7V in post-vaccine surveillance from The Gambia

Conceptual Art

Providing a re-examination of what Osborne identifies as a major turning point in contemporary art, this monograph takes a chronological and stylistic look at conceptual art from its “pre-history” (1950-1960) to contemporary practices that use conceptual strategies. Osborne surveys the development of the movement in relation to the social, cultural and political contexts within which it evolved. With extended captions, key works are compiled according to ten themes that also serve to present a collection of critical texts, artists’ statements, interviews and commentaries. Includes biographical notes on artists (6 p.) and authors (2 p.), a bibliography (2 p.) and an onomastic index (4 p.) Circa 150 bibl. ref

Infrared Studies of Epsilon Aurigae in Eclipse

We report here on a series of medium resolution spectro-photometric observations of the enigmatic long period eclipsing binary epsilon Aurigae, during its eclipse interval of 2009-2011, using near-infrared spectra obtained with SpeX on the Infrared Telescope Facility (IRTF), mid-infrared spectra obtained with BASS on AOES and IRTF, MIRSI on IRTF, and MIRAC4 on the MMT, along with mid-infrared photometry using MIRSI on IRTF and MIRAC4 on the MMT, plus 1995-2000 timeframe published photometry and data obtained with Denver's TNTCAM2 at WIRO. The goals of these observations included: (1) comparing eclipse depths with prior eclipse data, (2) confirming the re-appearance of CO absorption bands at and after mid-eclipse, associated with sublimation in the disk, (3) seeking evidence for any mid-infrared solid state spectral features from particles in the disk, and (4) providing evidence that the externally irradiated disk has azimuthal temperature differences. IR eclipse depths appear similar to those observed during the most recent (1983) eclipse, although evidence for post-mid-eclipse disk temperature increase is present, due to F star heated portions of the disk coming into view. Molecular CO absorption returned 57 days after nominal mid-eclipse, but was not detected at mid-eclipse plus 34 days, narrowing the association with differentially heated sub-regions in the disk. Transient He I 10830A absorption was detected at mid-eclipse, persisting for at least 90 days thereafter, providing a diagnostic for the hot central region. The lack of solid-state features in Spitzer Infrared Spectrograph, BASS, and MIRAC spectra to date suggests the dominance of large particles (micron-sized) in the disk. Based on these observations, mid-infrared studies out of eclipse can directly monitor and map the disk thermal changes, and better constrain disk opacity and thermal conductivity

Activity-Induced Remodeling of Olfactory Bulb Microcircuits Revealed by Monosynaptic Tracing

The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits

Structural and non-coding variants increase the diagnostic yield of clinical whole genome sequencing for rare diseases

BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome.METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants.RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving.CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.</p