79 research outputs found
Locomotion Policy Guided Traversability Learning using Volumetric Representations of Complex Environments
Despite the progress in legged robotic locomotion, autonomous navigation in
unknown environments remains an open problem. Ideally, the navigation system
utilizes the full potential of the robots' locomotion capabilities while
operating within safety limits under uncertainty. The robot must sense and
analyze the traversability of the surrounding terrain, which depends on the
hardware, locomotion control, and terrain properties. It may contain
information about the risk, energy, or time consumption needed to traverse the
terrain. To avoid hand-crafted traversability cost functions we propose to
collect traversability information about the robot and locomotion policy by
simulating the traversal over randomly generated terrains using a physics
simulator. Thousand of robots are simulated in parallel controlled by the same
locomotion policy used in reality to acquire 57 years of real-world locomotion
experience equivalent. For deployment on the real robot, a sparse convolutional
network is trained to predict the simulated traversability cost, which is
tailored to the deployed locomotion policy, from an entirely geometric
representation of the environment in the form of a 3D voxel-occupancy map. This
representation avoids the need for commonly used elevation maps, which are
error-prone in the presence of overhanging obstacles and multi-floor or
low-ceiling scenarios. The effectiveness of the proposed traversability
prediction network is demonstrated for path planning for the legged robot
ANYmal in various indoor and natural environments.Comment: accepted for 2022 IEEE/RSJ International Conference on Intelligent
Robots and Systems (IROS 2022
Learning Agile Locomotion on Risky Terrains
Quadruped robots have shown remarkable mobility on various terrains through
reinforcement learning. Yet, in the presence of sparse footholds and risky
terrains such as stepping stones and balance beams, which require precise foot
placement to avoid falls, model-based approaches are often used. In this paper,
we show that end-to-end reinforcement learning can also enable the robot to
traverse risky terrains with dynamic motions. To this end, our approach
involves training a generalist policy for agile locomotion on disorderly and
sparse stepping stones before transferring its reusable knowledge to various
more challenging terrains by finetuning specialist policies from it. Given that
the robot needs to rapidly adapt its velocity on these terrains, we formulate
the task as a navigation task instead of the commonly used velocity tracking
which constrains the robot's behavior and propose an exploration strategy to
overcome sparse rewards and achieve high robustness. We validate our proposed
method through simulation and real-world experiments on an ANYmal-D robot
achieving peak forward velocity of >= 2.5 m/s on sparse stepping stones and
narrow balance beams. Video: youtu.be/Z5X0J8OH6z4Comment: 8 pages, 11 figure
PIP3-dependent macropinocytosis is incompatible with chemotaxis
In eukaryotic chemotaxis, the mechanisms connecting external signals to the motile apparatus remain unclear. The role of the lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3) has been particularly controversial. PIP3 has many cellular roles, notably in growth control and macropinocytosis as well as cell motility. Here we show that PIP3 is not only unnecessary for Dictyostelium discoideum to migrate toward folate, but actively inhibits chemotaxis. We find that macropinosomes, but not pseudopods, in growing cells are dependent on PIP3. PIP3 patches in these cells show no directional bias, and overall only PIP3-free pseudopods orient up-gradient. The pseudopod driver suppressor of cAR mutations (SCAR)/WASP and verprolin homologue (WAVE) is not recruited to the center of PIP3 patches, just the edges, where it causes macropinosome formation. Wild-type cells, unlike the widely used axenic mutants, show little macropinocytosis and few large PIP3 patches, but migrate more efficiently toward folate. Tellingly, folate chemotaxis in axenic cells is rescued by knocking out phosphatidylinositide 3-kinases (PI 3-kinases). Thus PIP3 promotes macropinocytosis and interferes with pseudopod orientation during chemotaxis of growing cells
Mammalian Inscuteable Regulates Spindle Orientation and Cell Fate in the Developing Retina
During mammalian neurogenesis, progenitor cells can divide with the mitotic spindle oriented parallel or perpendicular to the surface of the neuroepithelium. Perpendicular divisions are more likely to be asymmetric and generate one progenitor and one neuronal precursor. Whether the orientation of the mitotic spindle actually determines their asymmetric outcome is unclear. Here, we characterize a mammalian homolog of Inscuteable (mInsc), a key regulator of spindle orientation in Drosophila. mInsc is expressed temporally and spatially in a manner that suggests a role in orienting the mitotic spindle in the developing nervous system. Using retroviral RNAi in rat retinal explants, we show that downregulation of mInsc inhibits vertical divisions. This results in enhanced proliferation, consistent with a higher frequency of symmetric divisions generating two proliferating cells. Our results suggest that the orientation of neural progenitor divisions is important for cell fate specification in the retina and determines their symmetric or asymmetric outcome
Mammalian Inscuteable Regulates Spindle Orientation and Cell Fate in the Developing Retina
During mammalian neurogenesis, progenitor cells can divide with the mitotic spindle oriented parallel or perpendicular to the surface of the neuroepithelium. Perpendicular divisions are more likely to be asymmetric and generate one progenitor and one neuronal precursor. Whether the orientation of the mitotic spindle actually determines their asymmetric outcome is unclear. Here, we characterize a mammalian homolog of Inscuteable (mInsc), a key regulator of spindle orientation in Drosophila. mInsc is expressed temporally and spatially in a manner that suggests a role in orienting the mitotic spindle in the developing nervous system. Using retroviral RNAi in rat retinal explants, we show that downregulation of mInsc inhibits vertical divisions. This results in enhanced proliferation, consistent with a higher frequency of symmetric divisions generating two proliferating cells. Our results suggest that the orientation of neural progenitor divisions is important for cell fate specification in the retina and determines their symmetric or asymmetric outcome
Proton Pump Inhibitor Use and Efficacy of Nivolumab and Ipilimumab in Advanced Melanoma
The impact of proton pump inhibitors (PPIs) on clinical outcomes with first-line immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma was previously analyzed in the phase II study, CheckMate 069. This retrospective analysis utilized data from three phase II/III studies of first-line ICI therapy in untreated advanced melanoma: CheckMate 066, 067, and 069. All randomized patients with PPI use ≤ 30 days before initiating study treatment were included in the PPI-use subgroup. Possible associations between baseline PPI use and efficacy were evaluated within each treatment arm of each study using multivariable modeling. Approximately 20% of 1505 randomized patients across the studies reported baseline PPI use. The median follow-up was 52.6–58.5 months. Objective response rate (ORR), progression-free survival (PFS), and overall survival analyses provided insufficient evidence of a meaningful association between PPI use and efficacy outcomes with nivolumab-plus-ipilimumab, nivolumab, or ipilimumab therapy. In five of the six ICI treatment arms, 95% confidence intervals for odds ratios or hazard ratios traversed 1. Significant associations were observed in the CheckMate 069 combination arm between PPI use and poorer ORR and PFS. This multivariable analysis found insufficient evidence to support meaningful associations between PPI use and ICI efficacy in patients with advanced melanoma
A Dual Function for Prickle in Regulating Frizzled Stability during Feedback-Dependent Amplification of Planar Polarity
The core planar polarity pathway coordinates epithelial cell polarity during animal development, and loss of its activity gives rise to a range of defects, from aberrant morphogenetic cell movements to failure to correctly orient structures, such as hairs and cilia. The core pathway functions via a mechanism involving segregation of its protein components to opposite cells ends, where they form asymmetric intracellular complexes that couple cell-cell polarity. This segregation is a self-organizing process driven by feedback interactions between the core proteins themselves. Despite intense efforts, the molecular pathways underlying feedback have proven difficult to elucidate using conventional genetic approaches. Here we investigate core protein function during planar polarization of the Drosophila wing by combining quantitative measurements of protein dynamics with loss-of-function genetics, mosaic analysis, and temporal control of gene expression. Focusing on the key core protein Frizzled, we show that its stable junctional localization is promoted by the core proteins Strabismus, Dishevelled, Prickle, and Diego. In particular, we show that the stabilizing function of Prickle on Frizzled requires Prickle activity in neighboring cells. Conversely, Prickle in the same cell has a destabilizing effect on Frizzled. This destabilizing activity is dependent on the presence of Dishevelled and blocked in the absence of Dynamin and Rab5 activity, suggesting an endocytic mechanism. Overall, our approach reveals for the first time essential in vivo stabilizing and destabilizing interactions of the core proteins required for self-organization of planar polarity
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