Experimental Investigation of a 16-inch Impulse-type Supersonic-compressor Rotor

Performance data and characteristics of a 16-inch impulse-type supersonic-compressor rotor are presented. The experimental portion of this investigation was conducted in Freon-12. A peak pressure ratio of 3.6 was obtained with an adiabatic efficiency of 0.80 at design conditions. Performance was continuous from impulse operation, at open throttle, to shock-in-rotor operation at the stall condition

Decatransin, a novel natural product inhibiting protein translocation at the Sec61/SecY translocon

A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S. cerevisiae indicated that the Sec61 translocon, the machinery for protein translocation and membrane insertion at the endoplasmic reticulum, is the target. The profiles were similar to those of cyclic heptadepsipeptides of a distinct chemotype (HUN-7293/cotransin) that had previously been shown to inhibit cotranslational translocation at the mammalian Sec61 translocon. Unbiased, genome-wide mutagenesis followed by full-genome sequencing in both fungal and mammalian cells identified dominant mutations in Sec61p/Sec61α1 to confer resistance. Most, but not all, of these mutations affected inhibition by both chemotypes, despite an absence of structural similarity. Biochemical analysis confirmed inhibition of protein translocation into the endoplasmic reticulum of both co- and posttranslationally translocated substrates by both chemotypes, demonstrating a mechanism independent of a translating ribosome. Most interestingly, both chemotypes were found to also inhibit SecYEG, the bacterial Sec61 homolog. We suggest "decatransin" as the name for this novel decadepsipeptide translocation inhibitor

Adapting oecd aquatic toxicity tests for use with manufactured nanomaterials: key issues and consensus recommendations

The unique or enhanced properties of manufactured nanomaterials (MNs) suggest that their use in nanoenabled products will continue to increase. This will result in increased potential for human and environmental exposure to MNs during manufacturing, use, and disposal of nanoenabled products. Scientifically based risk assessment for MNs necessitates the development of reproducible, standardized hazard testing methods such as those provided by the Organisation of Economic Cooperation and Development (OECD). Currently, there is no comprehensive guidance on how best to address testing issues specific to MN particulate, fibrous, or colloidal properties. This paper summarizes the findings from an expert workshop convened to develop a guidance document that addresses the difficulties encountered when testing MNs using OECD aquatic and sediment test guidelines. Critical components were identified by workshop participants that require specific guidance for MN testing: preparation of dispersions, dose metrics, the importance and challenges associated with maintaining and monitoring exposure levels, and the need for reliable methods to quantify MNs in complex media. To facilitate a scientific advance in the consistency of nanoecotoxicology test results, we identify and discuss critical considerations where expert consensus recommendations were and were not achieved and provide specific research recommendations to resolve issues for which consensus was not reached. This process will enable the development of prescriptive testing guidance for MNs. Critically, we highlight the need to quantify and properly interpret and express exposure during the bioassays used to determine hazard values

Reliability of multi-site UK Biobank MRI brain phenotypes for the assessment of neuropsychiatric complications of SARS-CoV-2 infection: The COVID-CNS travelling heads study.

Funder: National Institute for Health Research (NIHR)INTRODUCTION: Magnetic resonance imaging (MRI) of the brain could be a key diagnostic and research tool for understanding the neuropsychiatric complications of COVID-19. For maximum impact, multi-modal MRI protocols will be needed to measure the effects of SARS-CoV-2 infection on the brain by diverse potentially pathogenic mechanisms, and with high reliability across multiple sites and scanner manufacturers. Here we describe the development of such a protocol, based upon the UK Biobank, and its validation with a travelling heads study. A multi-modal brain MRI protocol comprising sequences for T1-weighted MRI, T2-FLAIR, diffusion MRI (dMRI), resting-state functional MRI (fMRI), susceptibility-weighted imaging (swMRI), and arterial spin labelling (ASL), was defined in close approximation to prior UK Biobank (UKB) and C-MORE protocols for Siemens 3T systems. We iteratively defined a comparable set of sequences for General Electric (GE) 3T systems. To assess multi-site feasibility and between-site variability of this protocol, N = 8 healthy participants were each scanned at 4 UK sites: 3 using Siemens PRISMA scanners (Cambridge, Liverpool, Oxford) and 1 using a GE scanner (King's College London). Over 2,000 Imaging Derived Phenotypes (IDPs), measuring both data quality and regional image properties of interest, were automatically estimated by customised UKB image processing pipelines (S2 File). Components of variance and intra-class correlations (ICCs) were estimated for each IDP by linear mixed effects models and benchmarked by comparison to repeated measurements of the same IDPs from UKB participants. Intra-class correlations for many IDPs indicated good-to-excellent between-site reliability. Considering only data from the Siemens sites, between-site reliability generally matched the high levels of test-retest reliability of the same IDPs estimated in repeated, within-site, within-subject scans from UK Biobank. Inclusion of the GE site resulted in good-to-excellent reliability for many IDPs, although there were significant between-site differences in mean and scaling, and reduced ICCs, for some classes of IDP, especially T1 contrast and some dMRI-derived measures. We also identified high reliability of quantitative susceptibility mapping (QSM) IDPs derived from swMRI images, multi-network ICA-based IDPs from resting-state fMRI, and olfactory bulb structure IDPs from T1, T2-FLAIR and dMRI data. CONCLUSION: These results give confidence that large, multi-site MRI datasets can be collected reliably at different sites across the diverse range of MRI modalities and IDPs that could be mechanistically informative in COVID brain research. We discuss limitations of the study and strategies for further harmonisation of data collected from sites using scanners supplied by different manufacturers. These acquisition and analysis protocols are now in use for MRI assessments of post-COVID patients (N = 700) as part of the ongoing COVID-CNS study

STROBE-X: A probe-class mission for x-ray spectroscopy and timing on timescales from microseconds to years

We describe the Spectroscopic Time-Resolving Observatory for Broadband Energy X-rays (STROBE-X), a probeclass mission concept that will provide an unprecedented view of the X-ray sky, performing timing and spectroscopy over both a broad energy band (0.2-30 keV) and a wide range of timescales from microseconds to years. STROBE-X comprises two narrow-field instruments and a wide field monitor. The soft or low-energy band (0.2-12 keV) is covered by an array of lightweight optics (3-m focal length) that concentrate incident photons onto small solid-state detectors with CCD-level (85-175 eV) energy resolution, 100 ns time resolution, and low background rates. This technology has been fully developed for NICER and will be scaled up to take advantage of the longer focal length of STROBE-X. The higher-energy band (2-30 keV) is covered by large-area, collimated silicon drift detectors that were developed for the European LOFT mission concept. Each instrument will provide an order of magnitude improvement in effective area over its predecessor (NICER in the soft band and RXTE in the hard band). Finally, STROBE-X offers a sensitive wide-field monitor (WFM), both to act as a trigger for pointed observations of X-ray transients and also to provide high duty-cycle, high time-resolution, and high spectral-resolution monitoring of the variable X-ray sky. The WFM will boast approximately 20 times the sensitivity of the RXTE All-Sky Monitor, enabling multi-wavelength and multi-messenger investigations with a large instantaneous field of view. This mission concept will be presented to the 2020 Decadal Survey for consideration

Oxygen-Independent Stabilization of Hypoxia Inducible Factor (HIF)-1 during RSV Infection

BACKGROUND: Hypoxia-inducible factor 1 (HIF)-1alpha is a transcription factor that functions as master regulator of mammalian oxygen homeostasis. In addition, recent studies identified a role for HIF-1alpha as transcriptional regulator during inflammation or infection. Based on studies showing that respiratory syncytial virus (RSV) is among the most potent biological stimuli to induce an inflammatory milieu, we hypothesized a role of HIF-1alpha as transcriptional regulator during infections with RSV. METHODOLOGY, PRINCIPAL FINDINGS: We gained first insight from immunohistocemical studies of RSV-infected human pulmonary epithelia that were stained for HIF-1alpha. These studies revealed that RSV-positive cells also stained for HIF-1alpha, suggesting concomitant HIF-activation during RSV infection. Similarly, Western blot analysis confirmed an approximately 8-fold increase in HIF-1alpha protein 24 h after RSV infection. In contrast, HIF-1alpha activation was abolished utilizing UV-treated RSV. Moreover, HIF-alpha-regulated genes (VEGF, CD73, FN-1, COX-2) were induced with RSV infection of wild-type cells. In contrast, HIF-1alpha dependent gene induction was abolished in pulmonary epithelia following siRNA mediated repression of HIF-1alpha. Measurements of the partial pressure of oxygen in the supernatants of RSV infected epithelia or controls revealed no differences in oxygen content, suggesting that HIF-1alpha activation is not caused by RSV associated hypoxia. Finally, studies of RSV pneumonitis in mice confirmed HIF-alpha-activation in a murine in vivo model. CONCLUSIONS/SIGNIFICANCE: Taking together, these studies suggest hypoxia-independent activation of HIF-1alpha during infection with RSV in vitro and in vivo

The Case for Probe-class NASA Astrophysics Missions

Astrophysics spans an enormous range of questions on scales from individual planets to the entire cosmos. To address the richness of 21st century astrophysics requires a corresponding richness of telescopes spanning all bands and all messengers. Much scientific benefit comes from having the multi-wavelength capability available at the same time. Most of these bands,or measurement sensitivities, require space-based missions. Historically, NASA has addressed this need for breadth with a small number of flagship-class missions and a larger number of Explorer missions. While the Explorer program continues to flourish, there is a large gap between Explorers and strategic missions. A fortunate combination of new astrophysics technologies with new, high capacity, low dollar-per-kg to orbit launchers, and new satellite buses allow for cheaper missions with capabilities approaching strategic mission levels. NASA has recognized these developments by calling for Probe-class mission ideas for mission studies, spanning most of the electromagnetic spectrum from GeV gamma-rays to the far infrared, and the new messengers of neutrinos and ultra-high energy cosmic rays. The key insight from the Probes exercise is that order-of-magnitude advances in science performance metrics are possible across the board for initial total cost estimates in the range 500M-1B dollars