Enhancing 3D Autonomous Navigation Through Obstacle Fields: Homogeneous Localisation and Mapping, with Obstacle-Aware Trajectory Optimisation

Small flying robots have numerous potential applications, from quadrotors for search and rescue, infrastructure inspection and package delivery to free-flying satellites for assistance activities inside a space station. To enable these applications, a key challenge is autonomous navigation in 3D, near obstacles on a power, mass and computation constrained platform. This challenge requires a robot to perform localisation, mapping, dynamics-aware trajectory planning and control. The current state-of-the-art uses separate algorithms for each component. Here, the aim is for a more homogeneous approach in the search for improved efficiencies and capabilities. First, an algorithm is described to perform Simultaneous Localisation And Mapping (SLAM) with physical, 3D map representation that can also be used to represent obstacles for trajectory planning: Non-Uniform Rational B-Spline (NURBS) surfaces. Termed NURBSLAM, this algorithm is shown to combine the typically separate tasks of localisation and obstacle mapping. Second, a trajectory optimisation algorithm is presented that produces dynamically-optimal trajectories with direct consideration of obstacles, providing a middle ground between path planners and trajectory smoothers. Called the Admissible Subspace TRajectory Optimiser (ASTRO), the algorithm can produce trajectories that are easier to track than the state-of-the-art for flight near obstacles, as shown in flight tests with quadrotors. For quadrotors to track trajectories, a critical component is the differential flatness transformation that links position and attitude controllers. Existing singularities in this transformation are analysed, solutions are proposed and are then demonstrated in flight tests. Finally, a combined system of NURBSLAM and ASTRO are brought together and tested against the state-of-the-art in a novel simulation environment to prove the concept that a single 3D representation can be used for localisation, mapping, and planning

Racism Is a Life Issue Panel Discussion

Jul 28, 2020 A moderated discussion on racism and the culture of life with distinguished panelists G. Marcus Cole (Dean, Notre Dame Law School), Sen. Katrina Jackson (Louisiana State Senate), Ernest Morrell (University of Notre Dame), Gloria Purvis (EWTN Global Catholic Radio), Jacqueline Rivers (Harvard University), and Benjamin Watson (NFL Legend)

miR-1-5p targets TGF-βR1 and is suppressed in the hypertrophying hearts of rats with pulmonary arterial hypertension.

The microRNA miR-1 is an important regulator of muscle phenotype including cardiac muscle. Down-regulation of miR-1 has been shown to occur in left ventricular hypertrophy but its contribution to right ventricular hypertrophy in pulmonary arterial hypertension are not known. Previous studies have suggested that miR-1 may suppress transforming growth factor-beta (TGF-β) signalling, an important pro-hypertrophic pathway but only indirect mechanisms of regulation have been identified. We identified the TGF-β type 1 receptor (TGF-βR1) as a putative miR-1 target. We therefore hypothesized that miR-1 and TGF-βR1 expression would be inversely correlated in hypertrophying right ventricle of rats with pulmonary arterial hypertension and that miR-1 would inhibit TGF-β signalling by targeting TGF-βR1 expression. Quantification of miR-1 and TGF-βR1 in rats treated with monocrotaline to induce pulmonary arterial hypertension showed appropriate changes in miR-1 and TGF-βR1 expression in the hypertrophying right ventricle. A miR-1-mimic reduced enhanced green fluorescent protein expression from a reporter vector containing the TGF-βR1 3'- untranslated region and knocked down endogenous TGF-βR1. Lastly, miR-1 reduced TGF-β activation of a (mothers against decapentaplegic homolog) SMAD2/3-dependent reporter. Taken together, these data suggest that miR-1 targets TGF-βR1 and reduces TGF-β signalling, so a reduction in miR-1 expression may increase TGF-β signalling and contribute to cardiac hypertrophy

The lysosomal inhibitor, chloroquine, increases cell surface BMPR-II levels and restores BMP9 signalling in endothelial cells harbouring BMPR-II mutations.

Pulmonary arterial hypertension (PAH) is characterized by dysregulated pulmonary artery endothelial cell (PAEC) proliferation, apoptosis and permeability. Loss-of-function mutations in the bone morphogenetic protein receptor type-II (BMPR-II) are the most common cause of heritable PAH, usually resulting in haploinsufficiency. We previously showed that BMPR-II expression is regulated via a lysosomal degradative pathway. Here, we show that the antimalarial drug, chloroquine, markedly increased cell surface expression of BMPR-II protein independent of transcription in PAECs. Inhibition of protein synthesis experiments revealed a rapid turnover of cell surface BMPR-II, which was inhibited by chloroquine treatment. Chloroquine enhanced PAEC expression of BMPR-II following siRNA knockdown of the BMPR-II transcript. Using blood outgrowth endothelial cells (BOECs), we confirmed that signalling in response to the endothelial BMPR-II ligand, BMP9, is compromised in BOECs from patients harbouring BMPR-II mutations, and in BMPR-II mutant PAECs. Chloroquine significantly increased gene expression of BMP9-BMPR-II signalling targets Id1, miR21 and miR27a in both mutant BMPR-II PAECs and BOECs. These findings provide support for the restoration of cell surface BMPR-II with agents such as chloroquine as a potential therapeutic approach for heritable PAH

Targeting translational read-through of premature termination mutations in BMPR2 with PTC124 for pulmonary arterial hypertension

Pulmonary arterial hypertension is a fatal disorder of the lung circulation in which accumulation of vascular cells progressively obliterates the pulmonary arterioles. This results in sustained elevation in pulmonary artery pressure leading eventually to right heart failure. Approximately, 80% of familial and 20% of sporadic idiopathic pulmonary arterial hypertension cases are caused by mutations in the bone morphogenetic protein receptor type 2 (BMPR2). Nonsense mutations in BMPR2 are amongst the most common mutations found, where the insertion of a premature termination codon causes mRNA degradation via activation of the nonsense-mediated decay pathway leading to a state of haploinsufficiency. Ataluren (PTC124), a compound that permits ribosomal read-through of premature stop codons, has been previously reported to increase BMPR2 protein expression in cells derived from pulmonary arterial hypertension patients harbouring nonsense mutations. In this study, we characterised the effects of PTC124 on a range of nonsense BMPR2 mutations, focusing on the R584X mutation both in vitro and in vivo. Treatment with PTC124 partially restored BMPR2 protein expression in blood outgrowth endothelial cells isolated from a patient harbouring the R584X mutation. Furthermore, a downstream bone morphogenetic protein signalling target, Id1, was rescued by PTC124 treatment. Mutant cells also exhibited increased lipopolysaccharide-induced permeability, which was reversed by PTC124 treatment. Increased proliferation and apoptosis in R584X blood outgrowth endothelial cells were also significantly reduced by PTC124. Moreover, oral PTC124 increased lung BMPR2 protein expression in mice harbouring the R584X mutation (Bmpr2+/R584X). Our findings provide support for future experimental medicine studies of PTC124 in pulmonary arterial hypertension patients with specific nonsense BMPR2 mutations

Electromagnetic Evidence that SSS17a is the Result of a Binary Neutron Star Merger

11 hours after the detection of gravitational wave source GW170817 by the Laser Interferometer Gravitational-Wave Observatory and Virgo Interferometers, an associated optical transient SSS17a was discovered in the galaxy NGC 4993. While the gravitational wave data indicate GW170817 is consistent with the merger of two compact objects, the electromagnetic observations provide independent constraints of the nature of that system. Here we synthesize all optical and near-infrared photometry and spectroscopy of SSS17a collected by the One-Meter Two-Hemisphere collaboration. We find that SSS17a is unlike other known transients. The source is best described by theoretical models of a kilonova consisting of radioactive elements produced by rapid neutron capture (the r-process). We find that SSS17a was the result of a binary neutron star merger, reinforcing the gravitational wave result.Comment: 21 pages, 4 figures, accepted to Scienc

Discovery and Early Evolution of ASASSN-19bt, the First TDE Detected by TESS

We present the discovery and early evolution of ASASSN-19bt, a tidal disruption event (TDE) discovered by the All-Sky Automated Survey for Supernovae (ASAS-SN) at a distance of $d\simeq115$ Mpc and the first TDE to be detected by TESS. As the TDE is located in the TESS Continuous Viewing Zone, our dataset includes 30-minute cadence observations starting on 2018 July 25, and we precisely measure that the TDE begins to brighten $\sim8.3$ days before its discovery. Our dataset also includes 18 epochs of Swift UVOT and XRT observations, 2 epochs of XMM-Newton observations, 13 spectroscopic observations, and ground data from the Las Cumbres Observatory telescope network, spanning from 32 days before peak through 37 days after peak. ASASSN-19bt thus has the most detailed pre-peak dataset for any TDE. The TESS light curve indicates that the transient began to brighten on 2019 January 21.6 and that for the first 15 days its rise was consistent with a flux $\propto t^2$ power-law model. The optical/UV emission is well-fit by a blackbody SED, and ASASSN-19bt exhibits an early spike in its luminosity and temperature roughly 32 rest-frame days before peak and spanning up to 14 days that has not been seen in other TDEs, possibly because UV observations were not triggered early enough to detect it. It peaked on 2019 March 04.9 at a luminosity of $L\simeq1.3\times10^{44}$ ergs s$^{-1}$ and radiated $E\simeq3.2\times10^{50}$ ergs during the 41-day rise to peak. X-ray observations after peak indicate a softening of the hard X-ray emission prior to peak, reminiscent of the hard/soft states in X-ray binaries.Comment: 23 pages, 14 figures, 5 tables. A machine-readable table containing the host-subtracted photometry presented in this manuscript is included as an ancillary fil