Long-term determination of energetic electron precipitation into the atmosphere from AARDDVARK subionospheric VLF observations

We analyze observations of subionospherically propagating very low frequency (VLF) radio waves to determine outer radiation belt energetic electron precipitation (EEP) flux magnitudes. The radio wave receiver in Sodankylä, Finland (Sodankylä Geophysical Observatory) observes signals from the transmitter with call sign NAA (Cutler, Maine). The receiver is part of the Antarctic-Arctic Radiation-belt Dynamic Deposition VLF Atmospheric Research Konsortia (AARDDVARK). We use a near-continuous data set spanning November 2004 until December 2013 to determine the long time period EEP variations. We determine quiet day curves over the entire period and use these to identify propagation disturbances caused by EEP. Long Wave Propagation Code radio wave propagation modeling is used to estimate the precipitating electron flux magnitudes from the observed amplitude disturbances, allowing for solar cycle changes in the ambient D region and dynamic variations in the EEP energy spectra. Our method performs well during the summer months when the daylit ionosphere is most stable but fails during the winter. From the summer observations, we have obtained 693 days worth of hourly EEP flux magnitudes over the 2004–2013 period. These AARDDVARK-based fluxes agree well with independent satellite precipitation measurements during high-intensity events. However, our method of EEP detection is 10–50 times more sensitive to low flux levels than the satellite measurements. Our EEP variations also show good agreement with the variation in lower band chorus wave powers, providing some confidence that chorus is the primary driver for the outer belt precipitation we are monitoring

Electron multiplication CCD detector technology advancement for the WFIRST-AFTA coronagraph

The WFIRST-AFTA (Wide Field InfraRed Survey Telescope-Astrophysics Focused Telescope Asset) is a NASA space observatory. It will host two major astronomical instruments: a wide-field imager (WFI) to search for dark energy and carry out wide field near infrared (NIR) surveys, and a coronagraph instrument (CGI) to image and spectrally characterize extrasolar planets. In this paper, we discuss the work that has been carried out at JPL in advancing Electron Multiplying CCD (EMCCD) technology to higher flight maturity, with the goal of reaching a NASA technology readiness level of 6 (TRL-6) by early-to-mid 2016. The EMCCD has been baselined for both the coronagraph's imager and integral field spectrograph (IFS) based on its sub-electron noise performance at extremely low flux levels - the regime where the AFTA CGI will operate. We present results from a study that fully characterizes the beginning of life performance of the EMCCD. We also discuss, and present initial results from, a recent radiation test campaign that was designed and carried out to mimic the conditions of the WFIRST-AFTA space environment in an L2 orbit, where we sought to assess the sensor's end of life performance, particularly degradation of its charge transfer efficiency, in addition to other parameters such as dark current, electron multiplication gain, clock induced charge and read noise

Inorganic nitrate as a treatment for acute heart failure: a protocol for a single center, randomized, double-blind, placebo-controlled pilot and feasibility study

Abstract Background Acute heart failure (AHF) is a frequent reason for hospitalization worldwide and effective treatment options are limited. It is known that AHF is a condition characterized by impaired vasorelaxation, together with reduced nitric oxide (NO) bioavailability, an endogenous vasodilatory compound. Supplementation of inorganic sodium nitrate (NaNO3) is an indirect dietary source of NO, through bioconversion. It is proposed that oral sodium nitrate will favorably affect levels of circulating NO precursors (nitrate and nitrite) in AHF patients, resulting in reduced systemic vascular resistance, without significant hypotension. Methods and outcomes We propose a single center, randomized, double-blind, placebo-controlled pilot trial, evaluating the feasibility of sodium nitrate as a treatment for AHF. The primary hypothesis that sodium nitrate treatment will result in increased systemic levels of nitric oxide pre-cursors (nitrate and nitrite) in plasma, in parallel with improved vasorelaxation, as assessed by non-invasively derived systemic vascular resistance index. Additional surrogate measures relevant to the known pathophysiology of AHF will be obtained in order to assess clinical effect on dyspnea and renal function. Discussion The results of this study will provide evidence of the feasibility of this novel approach and will be of interest to the heart failure community. This trial may inform a larger study

Compounds enhancing human sperm motility identified using a high-throughput phenotypic screening platform

STUDY QUESTION: Can a high-throughput screening (HTS) platform facilitate male fertility drug discovery? SUMMARY ANSWER: An HTS platform identified a large number of compounds that enhanced sperm motility. WHAT IS KNOWN ALREADY: Several efforts to find small molecules modulating sperm function have been performed but none have used high-throughput technology. STUDY DESIGN, SIZE, DURATION: Healthy donor semen samples were used and samples were pooled (3–5 donors per pool). Primary screening was performed singly; dose–response screening was performed in duplicate (using independent donor pools). PARTICIPANTS/MATERIALS, SETTING, METHODS: Spermatozoa isolated from healthy donors were prepared by density gradient centrifugation and incubated in 384-well plates with compounds (6.25 μM) to identify those compounds with enhancing effects on motility. Approximately 17 000 compounds from the libraries, ReFRAME, Prestwick, Tocris, LOPAC, CLOUD and MMV Pathogen Box, were screened. Dose–response experiments of screening hits were performed to confirm the enhancing effect on sperm motility. Experiments were performed in a university setting. MAIN RESULTS AND THE ROLE OF CHANCE: From our primary single concentration screening, 105 compounds elicited an enhancing effect on sperm motility compared to dimethylsulphoxide-treated wells. Confirmed enhancing compounds were grouped based on their annotated targets/target classes. A major target class, phosphodiesterase inhibitors, were identified, in particular PDE10A inhibitors as well as number of compounds not previously known to enhance human sperm motility, such as those related to GABA signalling. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Although this approach provides data about the activity of the compound, it is only a starting point. For example, further substantive experiments are necessary to provide a more comprehensive picture of each compound’s activity, the effect on the kinetics of the cell populations and subpopulations, and their potential mechanisms of action. Compounds have been tested with prepared donor spermatozoa, incubated under non-capacitating conditions, and only incubated with compounds for a relatively short period of time. Therefore, the effect of compounds under different conditions, for example in whole semen, for longer incubation times, or using samples from patient groups, may be different and require further study. All experiments were performed in vitro. WIDER IMPLICATIONS OF THE FINDINGS: This phenotypic screening assay identified a large number of compounds that increased sperm motility. In addition to furthering our understanding of human sperm function, for example identifying new avenues for discovery, we highlight potential compounds as promising start-point for a medicinal chemistry programme for potential enhancement of male fertility. Moreover, with disclosure of the results of screening, we present a substantial resource to inform further work in the field. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Bill and Melinda Gates Foundation, Scottish Funding Council and Scottish Universities Life Science Alliance. C.L.R.B. is Editor for RBMO. C.L.R.B. receives funding from Chief Scientists Office (Scotland), ESHRE and Genus PLC, consulting fees from Exscientia and lecture fees from Cooper Surgical and Ferring. S.M.d.S. is an Associate Editor of Human Reproduction, and an Associate Editor of Reproduction and Fertility. S.M.d.S. receives funding from Cooper Surgical and British Dietetic Society. No other authors declared a COI