The Flying Monkey: a Mesoscale Robot that can Run, Fly, and Grasp

The agility and ease of control make a quadrotor aircraft an attractive platform for studying swarm behavior, modeling, and control. The energetics of sustained flight for small aircraft, however, limit typical applications to only a few minutes. Adding payloads – and the mechanisms used to manipulate them – reduces this flight time even further. In this paper we present the flying monkey, a novel robot platform having three main capabilities: walking, grasping, and flight. This new robotic platform merges one of the world’s smallest quadrotor aircraft with a lightweight, single-degree-of-freedom walking mechanism and an SMA-actuated gripper to enable all three functions in a 30 g package. The main goal and key contribution of this paper is to design and prototype the flying monkey that has increased mission life and capabilities through the combination of the functionalities of legged and aerial roots.National Science Foundation (U.S.) (IIS-1138847)National Science Foundation (U.S.) (EFRI-124038)National Science Foundation (U.S.) (CCF-1138967)United States. Army Research Laboratory (W911NF-08-2-0004)Wyss Institute for Biologically Inspired Engineerin

Mutant SOD1 impairs axonal transport of choline acetyltransferase and acetylcholine release by sequestering KAP3

Mutations in the superoxide dismutase 1 (sod1) gene cause familial amyotrophic lateral sclerosis (FALS), likely due to the toxic properties of misfolded mutant SOD1 protein. Here we demonstrated that, starting from the pre-onset stage of FALS, misfolded SOD1 species associates specifically with kinesin-associated protein 3 (KAP3) in the ventral white matter of SOD1G93A-transgenic mouse spinal cord. KAP3 is a kinesin-2 subunit responsible for binding to cargos including choline acetyltransferase (ChAT). Motor axons in SOD1G93A-Tg mice also showed a reduction in ChAT transport from the pre-onset stage. By employing a novel FALS modeling system using NG108-15 cells, we showed that microtubule-dependent release of acetylcholine was significantly impaired by misfolded SOD1 species. Furthermore, such impairment was able to be normalized by KAP3 overexpression. KAP3 was incorporated into SOD1 aggregates in human FALS cases as well. These results suggest that KAP3 sequestration by misfolded SOD1 species and the resultant inhibition of ChAT transport play a role in the dysfunction of ALS

Nicotine exploits a COPI-mediated process for chaperone-mediated up-regulation of its receptors

Chronic exposure to nicotine up-regulates high sensitivity nicotinic acetylcholine receptors (nAChRs) in the brain. This up-regulation partially underlies addiction and may also contribute to protection against Parkinson’s disease. nAChRs containing the α6 subunit (α6* nAChRs) are expressed in neurons in several brain regions, but comparatively little is known about the effect of chronic nicotine on these nAChRs. We report here that nicotine up-regulates α6* nAChRs in several mouse brain regions (substantia nigra pars compacta, ventral tegmental area, medial habenula, and superior colliculus) and in neuroblastoma 2a cells. We present evidence that a coat protein complex I (COPI)-mediated process mediates this up-regulation of α6* or α4* nAChRs but does not participate in basal trafficking. We show that α6β2β3 nAChR up-regulation is prevented by mutating a putative COPI-binding motif in the β3 subunit or by inhibiting COPI. Similarly, a COPI-dependent process is required for up-regulation of α4β2 nAChRs by chronic nicotine but not for basal trafficking. Mutation of the putative COPI-binding motif or inhibition of COPI also results in reduced normalized Förster resonance energy transfer between α6β2β3 nAChRs and εCOP subunits. The discovery that nicotine exploits a COPI-dependent process to chaperone high sensitivity nAChRs is novel and suggests that this may be a common mechanism in the up-regulation of nAChRs in response to chronic nicotine

Evolutionary history of Pacific salmon in dynamic environments

Contemporary evolution of Pacific salmon (Oncorhynchus spp.) is best viewed in the context of the evolutionary history of the species and the dynamic ecosystems they inhabit. Speciation was complete by the late Miocene, leaving c. six million years for intraspecific diversification. Following the most recent glacial maximum, large areas became available for recolonization. Current intraspecific diversity is thus the product of recent evolution overlaid onto divergent historical lineages forged during recurrent episodes of Pleistocene glaciation. In northwestern North America, dominant habitat features have been relatively stable for the past 5000 years, but salmon ecosystems remain dynamic because of disturbance regimes (volcanic eruptions, landslides, wildfires, floods, variations in marine and freshwater productivity) that occur on a variety of temporal and spatial scales. These disturbances both create selective pressures for adaptive responses by salmon and inhibit long-term divergence by periodically extirpating local populations and creating episodic dispersal events that erode emerging differences. Recent anthropogenic changes are replicated pervasively across the landscape and interrupt processes that allow natural habitat recovery. If anthropogenic changes can be shaped to produce disturbance regimes that more closely mimic (in both space and time) those under which the species evolved, Pacific salmon should be well-equipped to deal with future challenges, just as they have throughout their evolutionary history

Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer's disease: a longitudinal observational study

BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer's pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer's disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer's disease. METHODS: We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer's disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR>0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models. FINDINGS: In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF Aβ42 (β=–4·28 × 10^{–2} [SE 0·013], p=0·0012), but not high cortical uptake in PiB-PET (β=–5·51 × 10^{–3} [0·011], p=0·63), was the only predictor of an augmented annual rate of subsequent increase in soluble TREM2. Augmented annual rates of increase in soluble TREM2 were associated with a diminished rate of decrease in amyloid deposition, as measured by Aβ42 in CSF (r=0·56 [0·22], p=0·011), in presymptomatic carriers of pathogenic variants, and with diminished annual rate of increase in PiB-PET (r=–0·67 [0·25], p=0·0060) in symptomatic carriers of pathogenic variants. Presymptomatic carriers of pathogenic variants with annual rates of increase in soluble TREM2 lower than the median showed a correlation between enhanced annual rates of increase in p-tau in CSF and augmented annual rates of increase in PiB-PET signal (r=0·45 [0·21], p=0·035), that was not observed in those with rates of increase in soluble TREM2 higher than the median. Furthermore, presymptomatic carriers of pathogenic variants with rates of increase in soluble TREM2 above or below the median had opposite associations between Aβ42 in CSF and PiB-PET uptake when assessed longitudinally. Augmented annual rates of increase in soluble TREM2 in presymptomatic carriers of pathogenic variants correlated with decreased cortical shrinkage in the precuneus (r=0·46 [0·22]), p=0·040) and diminished cognitive decline (r=0·67 [0·22], p=0·0020). INTERPRETATION: Our findings in autosomal dominant Alzheimer's disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in Aβ aggregation and further support the role of TREM2 on Aβ plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing

The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition

Design and control of miniature air-and-ground vehicles

Thesis: S.M., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2017.Cataloged from PDF version of thesis.Includes bibliographical references (pages 89-92).The ability to both fly and drive is a superpower that few robots have. This thesis describes the design and control of two miniature air-and-ground vehicles, the "Flying Monkey" and the "Flying Car." The Flying Monkey was developed to demonstrate the viability and utility of miniature air-and-ground vehicles. The final design weighs 30g yet is capable of crawling, grasping, and flying. It features a novel crawling and grasping mechanism that consists of 66 linkages yet weighs only 5.1 grams. Although the crawler is capable of only forward and backward motion, we designed a controller that uses the yaw torque of the propellers to give the Flying Monkey two degrees of freedom on the ground. In experiments we demonstrated that the Flying Monkey is able to grasp small objects, fly over obstacles, and crawl through narrow pipes. The Flying Car was designed as a swarm vehicle to test multi-robot path planning. We therefore made the Flying Car as simple and robust as possible, built a small swarm of them, and tested them in a miniature town. We present two of the first algorithms for multi-robot path planning for air-and-ground vehicles, one based on priority planning and the other based on multi-commodity network flow. Thus, by designing and testing robots, controllers, and algorithms for miniature air-and-ground vehicles, this thesis hopes to serve as a starting point for future research in this promising area of study.by Minoru Brandon Araki.S.M

Learning to Plan by Learning Rules

Many environments involve following rules and tasks; for example, a chef cooking a dish follows a recipe, and a person driving follows rules of the road. People are naturally fluent with rules: we can learn rules efficiently; we can follow rules; we can interpret rules and explain them to others; and we can rapidly adjust to modified rules such as a new recipe without needing to relearn everything from scratch. By contrast, deep reinforcement learning (DRL) algorithms are ill-suited to learning policies in rule-based environments, as satisfying rules often involves executing lengthy tasks with sparse rewards. Furthermore, learned DRL policies are difficult if not impossible to interpret and are not composable. The aim of this thesis is to develop a reinforcement learning framework for rule-based environments that can efficiently learn policies that are interpretable, satisfying, and composable. We achieve interpretability by representing rules as automata or Linear Temporal Logic (LTL) formulas in a hierarchical Markov Decision Process (MDP). We achieve satisfaction by planning over the hierarchical MDP using a modified version of value iteration. We achieve composability by building off of a hierarchical reinforcement learning (HRL) framework called the options framework, in which low-level options can be composed arbitrarily. And lastly, we achieve data-efficient learning by integrating our HRL framework into a Bayesian model that can infer a distribution over LTL formulas given a low-level environment and a set of expert trajectories. We demonstrate the effectiveness of our approach via a number of rule-learning and planning experiments in both simulated and real-world environments.Ph.D

Safe Local Navigation for Visually Impaired Users with a Time-of-Flight and Haptic Feedback Device

This paper presents ALVU (Array of Lidars and Vibrotactile Units), a contactless, intuitive, hands-free, and discreet wearable device that allows visually impaired users to detect low- and high-hanging obstacles, as well as physical boundaries in their immediate environment. The solution allows for safe local navigation in both confined and open spaces by enabling the user to distinguish free space from obstacles. The device presented is composed of two parts: a sensor belt and a haptic strap. The sensor belt is an array of time-of-flight distance sensors worn around the front of a user’s waist, and the pulses of infrared light provide reliable and accurate measurements of the distances between the user and surrounding obstacles or surfaces. The haptic strap communicates the measured distances through an array of vibratory motors worn around the user’s upper abdomen, providing haptic feedback. The linear vibration motors are combined with a point-loaded pretensioned applicator to transmit isolated vibrations to the user. We validated the device’s capability in an extensive user study entailing 162 trials with 12 blind users. Users wearing the device successfully walked through hallways, avoided obstacles, and detected staircases. Keywords: haptic interfaces; navigation; robot sensing systems; vibrations; belts; sensor arrays; cameras; assistive device; sightless navigation; human-robot interaction; perception; haptic feedback arrayNational Science Foundation (U.S.) (Grant IIS1226883