Simulating Fleet Noise for Notional UAM Vehicles and Operations in New York

This paper presents the results of systems-level simulations using Metrosim that were conducted for notional Urban Air Mobility (UAM)-style vehicles analyzed for two different scenarios for New York (NY). UAM is an aviation industry term for passenger or cargo-carrying air transportation services, which are often automated, operating in an urban/city environment. UAM-style vehicles are expected to use vertical takeoff and landing with fixed wing cruise flight. Metrosim is a metroplex-wide route and airport planning tool that can also be used in standalone mode as a simulation tool. The scenarios described and reported in this paper were used to evaluate a fleet noise prediction capability for this tool. The work was a collaborative effort between the National Aeronautics and Space Administration (NASA), Intelligent Automation, Inc (IAI), and the Port Authority of New York and New Jersey (PANYNJ). One scenario was designed to represent an expanded air-taxi operation from existing helipads around Manhattan to the major New York airports. The other case represented a farther term vision case with commuters using personal air vehicles to hub locations just outside New York, with an air-taxi service running frequent connector trips to a few key locations inside Manhattan. For both scenarios, the trajectories created for the entire fleet were passed to the Aircraft Environmental Design Tool (AEDT) to generate Day-Night Level (DNL) noise contours for inspection. Without data for actual UAM vehicles available, surrogate AEDT empirical Noise-Power-Distance (NPD) tables used a similar sized current day helicopter as the Baseline, and a version of that same data linearly scaled as a first guess at possible UAM noise data. Details are provided for each of the two scenario configurations, and the output noise contours are presented for the Baseline and reduced noise DNL cases

De Novo Pathogenic Variants in N-cadherin Cause a Syndromic Neurodevelopmental Disorder with Corpus Callosum, Axon, Cardiac, Ocular, and Genital Defects

International audienceCadherins constitute a family of transmembrane proteins that mediate calcium-dependent cell-cell adhesion. The extracellular domain of cadherins consists of extracellular cadherin (EC) domains, separated by calcium binding sites. The EC interacts with other cadherin molecules in cis and in trans to mechanically hold apposing cell surfaces together. CDH2 encodes N-cadherin, whose essential roles in neural development include neuronal migration and axon pathfinding. However, CDH2 has not yet been linked to a Mendelian neurodevelopmental disorder. Here, we report de novo heterozygous pathogenic variants (seven missense, two frameshift) in CDH2 in nine individuals with a syndromic neurodevelopmental disorder characterized by global developmental delay and/or intellectual disability, variable axon pathfinding defects (corpus callosum agenesis or hypoplasia, mirror movements, Duane anomaly), and ocular, cardiac, and genital anomalies. All seven missense variants (c.1057G>A [p.Asp353Asn]; c.1789G>A [p.Asp597Asn]; c.1789G>T [p.Asp597Tyr]; c.1802A>C [p.Asn601Thr]; c.1839C>G [p.Cys613Trp]; c.1880A>G [p.Asp627Gly]; c.2027A>G [p.Tyr676Cys]) result in substitution of highly conserved residues, and six of seven cluster within EC domains 4 and 5. Four of the substitutions affect the calcium-binding site in the EC4-EC5 interdomain. We show that cells expressing these variants in the EC4-EC5 domains have a defect in cell-cell adhesion; this defect includes impaired binding in trans with N-cadherin-WT expressed on apposing cells. The two frameshift variants (c.2563_2564delCT [p.Leu855Valfs∗4]; c.2564_2567dupTGTT [p.Leu856Phefs∗5]) are predicted to lead to a truncated cytoplasmic domain. Our study demonstrates that de novo heterozygous variants in CDH2 impair the adhesive activity of N-cadherin, resulting in a multisystemic developmental disorder, that could be named ACOG syndrome (agenesis of corpus callosum, axon pathfinding, cardiac, ocular, and genital defects)