Cryogenic Propellant Storage and Transfer Technology Demonstration: Prephase A Government Point-of-Departure Concept Study

The primary purpose of this study was to define a point-of-departure prephase A mission concept for the cryogenic propellant storage and transfer technology demonstration mission to be conducted by the NASA Office of the Chief Technologist (OCT). The mission concept includes identification of the cryogenic propellant management technologies to be demonstrated, definition of a representative mission timeline, and definition of a viable flight system design concept. The resulting mission concept will serve as a point of departure for evaluating alternative mission concepts and synthesizing the results of industry- defined mission concepts developed under the OCT contracted studie

Lynx Mission Concept Status

Lynx is a concept under study for prioritization in the 2020 Astrophysics Decadal Survey. Providing orders of magnitude increase in sensitivity over Chandra, Lynx will examine the first black holes and their galaxies, map the large-scale structure and galactic halos, and shed new light on the environments of young stars and their planetary systems. In order to meet the Lynx science goals, the telescope consists of a high-angular resolution optical assembly complemented by an instrument suite that may include a High Definition X-ray Imager, X-ray Microcalorimeter and an X-ray Grating Spectrometer. The telescope is integrated onto the spacecraft to form a comprehensive observatory concept. Progress on the formulation of the Lynx telescope and observatory configuration is reported in this paper

Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder

International audienceGenetic risk factors for autism spectrum disorder (ASD) have yet to be fully elucidated. Postzygotic mosaic mutations (PMMs) have been implicated in several neurodevelopmental disorders and overgrowth syndromes. By leveraging whole-exome sequencing data on a large family-based ASD cohort, the Simons Simplex Collection, we systematically evaluated the potential role of PMMs in autism risk. Initial re-evaluation of published single-nucleotide variant (SNV) de novo mutations showed evidence consistent with putative PMMs for 11% of mutations. We developed a robust and sensitive SNV PMM calling approach integrating complementary callers, logistic regression modeling, and additional heuristics. In our high-confidence call set, we identified 470 PMMs in children, increasing the proportion of mosaic SNVs to 22%. Probands have a significant burden of synonymous PMMs and these mutations are enriched for computationally predicted impacts on splicing. Evidence of increased missense PMM burden was not seen in the full cohort. However, missense burden signal increased in subcohorts of families where probands lacked nonsynonymous germline mutations, especially in genes intolerant to mutations. Parental mosaic mutations that were transmitted account for 6.8% of the presumed de novo mutations in the children. PMMs were identified in previously implicated high-confidence neurodevelopmental disorder risk genes, such as CHD2, CTNNB1, SCN2A, and SYNGAP1, as well as candidate risk genes with predicted functions in chromatin remodeling or neurodevelopment, including ACTL6B, BAZ2B, COL5A3, SSRP1, and UNC79. We estimate that PMMs potentially contribute risk to 3%-4% of simplex ASD case subjects and future studies of PMMs in ASD and related disorders are warranted

Synthesis and reactions of 4-aryloxyflavans

4α-Aryloxyflavans unsubstituted in ring A have been synthesised by the reaction of phenols with flavan-4β-ols in the presence of boron trifluoride in ether. If reaction times are prolonged beyond disappearance of the starting 4β-ols, thermodynamic control leads to 4-arylflavans and the yields of 4-aryloxyflavans are negligible. 4-Arylflavans are the sole products when the catalyst is toluene-p-sulphonic acid. Thermal decomposition of flavan-4β-yl phenol carbonate in the presence of phenols affords a synthesis of 4α-aryloxyflavans free from 4-arylflavans. Syntheses of 7-methoxy-4α-aryloxyflavans have not been successful, nor can 4-aryloxyflavan-3-ols be obtained from 3,4-diols by these methods. The 4-aryloxyflavans react rapidly with acids to yield 4-carbocations which can be trapped by a variety of nucleophiles yielding 4α-ols with water, 4α-alkoxyflavans with alcohols, 4α-arylflavans with phenols, and 4α-sulphides with thiols. 2,3-cis-Flav-3-ene epoxide reacts with phenols to give 2,3-cis-3,4-cis-4-aryloxyflavan-3-ols and with sodium salts of phenols to give 2,3-cis-3,4-trans-4-aryloxyflavan-3-ols. The 2,3-trans-epoxide similarly gives the 2,3-trans-4-aryloxyflavan-3-ols. A biflavonoid containing a 4-aryloxy link has been synthesised from the 2,3-trans-epoxide and 7-hydroxyflavan-4-one. A series of 2,3-trans-4′-methoxy-4-aryloxyflavan-3-ols has been synthesised from crude 2,3-trans-4′-methoxyflav-3-ene epoxide. The substitution of a methoxy group into position 7 of the flavonoid A-ring prevented the preparation of the epoxides, but the action of N-bromosuccinimide and sodium acetate in acetic anhydride and acetic acid on 7,4′-dimethoxyflav-3-ene gave 2,3-cis- and 2,3-trans-4-acetoxy-3-bromo-7,4′-dimethoxy-flavans, the latter of which was converted by the action of sodium salts of phenols into the expected 4-aryloxyflavan-3-ols. 5,7,3′,4′-Tetramethoxyflav-3-ene gave nuclear brominated products even with N-bromosuccinimide; thus the synthesis of 5,7,3′,4′-tetramethoxy-4-aryloxyflavan-3-ols has not been possible by this method