Information-Theoretic Active Perception for Multi-Robot Teams

Multi-robot teams that intelligently gather information have the potential to transform industries as diverse as agriculture, space exploration, mining, environmental monitoring, search and rescue, and construction. Despite large amounts of research effort on active perception problems, there still remain significant challenges. In this thesis, we present a variety of information-theoretic control policies that enable teams of robots to efficiently estimate different quantities of interest. Although these policies are intractable in general, we develop a series of approximations that make them suitable for real time use. We begin by presenting a unified estimation and control scheme based on Shannon\u27s mutual information that lets small teams of robots equipped with range-only sensors track a single static target. By creating approximate representations, we substantially reduce the complexity of this approach, letting the team track a mobile target. We then scale this approach to larger teams that need to localize a large and unknown number of targets. We also examine information-theoretic control policies to autonomously construct 3D maps with ground and aerial robots. By using Cauchy-Schwarz quadratic mutual information, we show substantial computational improvements over similar information-theoretic measures. To map environments faster, we adopt a hierarchical planning approach which incorporates trajectory optimization so that robots can quickly determine feasible and locally optimal trajectories. Finally, we present a high-level planning algorithm that enables heterogeneous robots to cooperatively construct maps

Organic indoor location : infrastructure and applications

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2010.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (p. 55-57).We describe OIL, a system that uses the existing wireless infrastructure of a building to enable a mobile device to discover its indoor location. One of the main goals behind OIL is to enable non-expert users to contribute the data that is required for localization. Toward this we have developed (1) a server-client architecture for aggregating and distributing data; (2) a caching scheme that enables client devices to estimate indoor location; (3) a simple user interface for contributing data; and (4) a way to indicate how uncertain localization estimates are. We evaluate our system with a nine-day, nineteen-person user study that took place on campus as well as a deployment of the system at an off-campus long-term specialized care facility. We also describe how to use a person's indoor location trace (i.e. the rooms they had visited and the times of each visit) to build a content-based recommendation system for academic seminars. Such a system would learn about a user's preferences implicitly, placing no burden on the user. We evaluate a prototype recommendation system based on data gathered from a user study in which participants ranked seminars.by Benjamin W. Charrow.M.Eng

In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models

Gaucher disease is a lysosomal storage disease caused by mutations in acid β-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers—verapamil and diltiazem—have been reported to modulate endoplasmic reticulum (ER) folding, trafficking, and activity of GCase in human Gaucher disease fibroblasts. Similarly, these LTCC blockers were tested with cultured skin fibroblasts from homozygous point-mutated GCase mice (V394L, D409H, D409V, and N370S) with the effect of enhancing of GCase activity. Correspondingly, diltiazem increased GCase protein and facilitated GCase trafficking to the lysosomes of these cells. The in vivo effects of diltiazem on GCase were evaluated in mice homozygous wild-type (WT), V394L and D409H. In D409H homozygotes diltiazem (10 mg/kg/d via drinking water or 50–200 mg/kg/d intraperitoneally) had minor effects on increasing GCase activity in brain and liver (1.2-fold). Diltiazem treatment (10 mg/kg/d) had essentially no effect on WT and V394L GCase protein or activity levels (<1.2-fold) in liver. These results show that LTCC blockers had the ex vivo effects of increasing GCase activity and protein in the mouse fibroblasts, but these effects did not translate into similar changes in vivo even at very high drug doses

Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat

Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes

Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat

BACKGROUND Fabry's disease, an X-linked disorder of lysosomal alpha-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of alpha-galactosidase, increasing enzyme trafficking to lysosomes. METHODS The initial assay of mutant alpha-galactosidase forms that we used to categorize 67 patients with Fabry's disease for randomization to 6 months of double-blind migalastat or placebo (stage 1), followed by open-label migalastat from 6 to 12 months (stage 2) plus an additional year, had certain limitations. Before unblinding, a new, validated assay showed that 50 of the 67 participants had mutant alpha-galactosidase forms suitable for targeting by migalastat. The primary end point was the percentage of patients who had a response (>= 50\% reduction in the number of globotriaosylceramide inclusions per kidney interstitial capillary) at 6 months. We assessed safety along with disease substrates and renal, cardiovascular, and patient-reported outcomes. RESULTS The primary end-point analysis, involving patients with mutant alpha-galactosidase forms that were suitable or not suitable for migalastat therapy, did not show a significant treatment effect: 13 of 32 patients (41\%) who received migalastat and 9 of 32 patients (28\%) who received placebo had a response at 6 months (P = 0.30). Among patients with suitable mutant alpha-galactosidase who received migalastat for up to 24 months, the annualized changes from baseline in the estimated glomerular filtration rate (GFR) and measured GFR were -0.30 +/- 0.66 and -1.51 +/- 1.33 ml per minute per 1.73 m(2) of body-surface area, respectively. The left-ventricular-mass index decreased significantly from baseline (-7.7 g per square meter; 95\% confidence interval {[}CI], -15.4 to -0.01), particularly when left ventricular hypertrophy was present (-18.6 g per square meter; 95\% CI, -38.2 to 1.0). The severity of diarrhea, reflux, and indigestion decreased. CONCLUSIONS Among all randomly assigned patients (with mutant alpha-galactosidase forms that were suitable or not suitable for migalastat therapy), the percentage of patients who had a response at 6 months did not differ significantly between the migalastat group and the placebo group. (Funded by Amicus Therapeutics; ClinicalTrials.gov numbers, NCT00925301 {[}study AT1001-011] and NCT01458119 {[}study AT1001-041].

Structural aspects of therapeutic enzymes to treat metabolic disorders

10.1002/humu.21111Human Mutation30121591-1610HUMU