Nimbus-7 ERB Solar Analysis Tape (ESAT) user's guide

Seven years and five months of Nimbus-7 Earth Radiation Budget (ERB) solar data are available on a single ERB Solar Analysis Tape (ESAT). The period covered is November 16, 1978 through March 31, 1986. The Nimbus-7 satellite performs approximately 14 orbits per day and the ERB solar telescope observes the sun once per orbit as the satellite crosses the southern terminator. The solar data were carefully calibrated and screened. Orbital and daily mean values are given for the total solar irradiance plus other spectral intervals (10 solar channels in all). In addition, selected solar activity indicators are included on the ESAT. The ESAT User's Guide is an update of the previous ESAT User's Guide (NASA TM 86143) and includes more detailed information on the solar data calibration, screening procedures, updated solar data plots, and applications to solar variability. Details of the tape format, including source code to access ESAT, are included

Demonstration of on sky contrast improvement using the Modified Gerchberg-Saxton algorithm at the Palomar Observatory

We have successfully demonstrated significant improvements in the high contrast detection limit of the Well-Corrected Subaperture (WCS) using a number of steps aimed at reducing non-common path (NCP) wavefront errors, including the Autonomous Phase Retrieval Calibration (APRC) software package developed at the Jet Propulsion Laboratory (JPL) for the Palomar adaptive optics instrument (PALAO). APRC utilizes the Modified Gerchberg-Saxton (MGS) wavefront sensing algorithm, also developed at JPL. The WCS delivers such excellent correction of the atmosphere that NCP wavefront errors not sensed by PALAO but present at the coronagraphic image plane begin to factor heavily as a limit to contrast. The APRC program was implemented to reduce these NCP wavefront errors from 110 nm to 35 nm (rms) in the lab, and now these exceptional results have been extended to targets on the sky for the first time, leading to a significant suppression of speckle noise. Consequently we now report a contrast level of very nearly 1×10^(-4) at separations of 2λ/D before the data is post processed, and 1×10^(-5) after post processing. We describe here the major components of our instrument, the work done to improve the NCP wavefront errors, and the ensuing excellent on sky results, including the detection of the three exoplanets orbiting the star HR8799

Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum

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Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease

A GPBAR1 (TGR5) small molecule agonist shows specific inhibitory effects on myeloid cell activation in vitro and reduces experimental autoimmune encephalitis (EAE) in vivo.

GPBAR1 is a G protein-coupled receptor that is activated by certain bile acids and plays an important role in the regulation of bile acid synthesis, lipid metabolism, and energy homeostasis. Recent evidence suggests that GPBAR1 may also have important effects in reducing the inflammatory response through its expression on monocytes and macrophages. To further understand the role of GPBAR1 in inflammation, we generated a novel, selective, proprietary GPBAR1 agonist and tested its effectiveness at reducing monocyte and macrophage activation in vitro and in vivo. We have used this agonist, together with previously described agonists to study agonism of GPBAR1, and shown that they can all induce cAMP and reduce TLR activation-induced cytokine production in human monocytes and monocyte-derived macrophages in vitro. Additionally, through the usage of RNA sequencing (RNA-Seq), we identified a select set of genes that are regulated by GPBAR1 agonism during LPS activation. To further define the in vivo role of GPBAR1 in inflammation, we assessed GPBAR1 expression and found high levels on circulating mouse monocytes. Agonism of GPBAR1 reduced LPS-induced cytokine production in mouse monocytes ex vivo and serum cytokine levels in vivo. Agonism of GPBAR1 also had profound effects in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, where monocytes play an important role. Mice treated with the GPBAR1 agonist exhibited a significant reduction in the EAE clinical score which correlated with reduced monocyte and microglial activation and reduced trafficking of monocytes and T cells into the CNS. These data confirm the importance of GPBAR1 in controlling monocyte and macrophage activation in vivo and support the rationale for selective agonists of GPBAR1 in the treatment of inflammatory diseases