Integrated Debugging of Large Modular Robot Ensembles

Abstract — Creatively misquoting Thomas Hobbes, the process of software debugging is nasty, brutish, and all too long. This holds all the more true in robotics, which frequently involves concurrency, extensive nondeterminisism, event-driven components, complex state machines, and difficult platform limitations. Inspired by the challenges we have encountered while attempting to debug software on simulated ensembles of tens of thousands of modular robots, we have developed a new debugging tool particularly suited to the characteristics of highly parallel, event- and state-driven robotics software. Our state capture and introspection system also provides data that may be used in higher-level debugging tools as well. We report on the design of this promising debugging system, and on our experiences with it so far. I

PIM1 inhibition effectively enhances Plerixafor-induced HSC mobilization

The CXCL12/CXCR4 axis regulates the interaction of hematopoietic stem cells (HSCs) with the niche and interruption of this pathway mobilizes HSCs from the bone marrow. Therefore CXCR4 antagonists like plerixafor are clinically used to collect HSCs from patients who fail to mobilize HSCs in response to G-CSF. Nevertheless plerixafor mobilization fails in 30% of the patients and the collection window lasts only 4-6h. As the CXCR4 surface expression on HSCs is regulated by the serine/threonine kinase PIM1, we aimed to improve HSC mobilization by combining CXCR4 and PIM1 inhibition. We found that CXCR4 inhibition using plerixafor leads to a compensatory upregulation of CXCR4 surface expression on HSCs. This effect can be reverted by deficiency or inhibition of PIM1. Consequently, HSC mobilization using plerixafor is strongly enhanced in Pim1-deficient mice. Likewise, treatment of WT animals with plerixafor in combination with the pan-PIM-inhibitor LGB321 leads to increased HSC mobilization. Furthermore, Cxcl-12 expression as well as CXCR4 surface expression in CXCL12-abundant reticular (CAR) cells is dramatically decreased in Pim1- deficient mice, resulting in impaired retention of HSCs. Targeting PIM kinases in combination with CXCR4 inhibition could thus improve the collection of stem cells in patients at risk for poor mobilization

The neural substrate of spectral preference in Drosophila

Drosophila vision is mediated by inputs from three types of photoreceptor neurons; R1–R6 mediate achromatic motion detection, while R7 and R8 constitute two chromatic channels. Neural circuits for processing chromatic information are not known. Here, we identified the first-order interneurons downstream of the chromatic channels. Serial EM revealed that small-field projection neurons Tm5 and Tm9 receive direct synaptic input from R7 and R8, respectively, and indirect input from R1–R6, qualifying them to function as color-opponent neurons. Wide-field Dm8 amacrine neurons receive input from 13–16 UV-sensing R7s and provide output to projection neurons. Using a combinatorial expression system to manipulate activity in different neuron subtypes, we determined that Dm8 neurons are necessary and sufficient for flies to exhibit phototaxis toward ultraviolet instead of green light. We propose that Dm8 sacrifices spatial resolution for sensitivity by relaying signals from multiple R7s to projection neurons, which then provide output to higher visual centers

PRG-1 regulates synaptic plasticity via intracellular PP2A/β1-integrin signaling

Alterations in dendritic spine numbers are linked to deficits in learning and memory. While we previously revealed that postsynaptic plasticity-related gene 1 (PRG-1) controls lysophosphatidic acid (LPA) signaling at glutamatergic synapses via presynaptic LPA receptors, we now show that PRG-1 also affects spine density and synaptic plasticity in a cell-autonomous fashion via protein phosphatase 2A (PP2A)/β1-integrin activation. PRG-1 deficiency reduces spine numbers and β1-integrin activation, alters long-term potentiation (LTP), and impairs spatial memory. The intracellular PRG-1 C terminus interacts in an LPA-dependent fashion with PP2A, thus modulating its phosphatase activity at the postsynaptic density. This results in recruitment of adhesome components src, paxillin, and talin to lipid rafts and ultimately in activation of β1-integrins. Consistent with these findings, activation of PP2A with FTY720 rescues defects in spine density and LTP of PRG-1-deficient animals. These results disclose a mechanism by which bioactive lipid signaling via PRG-1 could affect synaptic plasticity and memory formation