Persistent mucus plugs in proximal airways are consequential for airflow limitation in asthma

BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments.METHODSCT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow.RESULTSThe length distribution of 778 annotated mucus plugs was multimodal, and a 12 mm length defined short ( stubby , ≤12 mm) and long ( stringy , \u3e12 mm) plug phenotypes. High mucus plug burden was disproportionately attributable to stringy mucus plugs. Mucus plugs localized predominantly to airway generations 6-9, and 47% of plugs in baseline scans persisted in the same airway for 3 years and fluctuated in length and volume. Mucus plugs in larger proximal generations had greater effects on spirometry measures than plugs in smaller distal generations, and a model of airflow that estimates the increased airway resistance attributable to plugs predicted a greater effect for proximal generations and more numerous mucus plugs.CONCLUSIONPersistent mucus plugs in proximal airway generations occur in asthma and demonstrate a stochastic process of formation and resolution over time. Proximal airway mucus plugs are consequential for airflow and are in locations amenable to treatment by inhaled muco-active drugs or bronchoscopy.TRIAL REGISTRATIONClinicaltrials.gov; NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01716494, and NCT01760915.FUNDINGAstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Sanofi-Genzyme-Regeneron, and TEVA provided financial support for study activities at the Coordinating and Clinical Centers beyond the third year of patient follow-up. These companies had no role in study design or data analysis, and the only restriction on the funds was that they be used to support the SARP initiative

Mobile Manipulation Platform for Autonomous Indoor Inspections in Low-Clearance Areas

Mobile manipulators have been used for inspection, maintenance and repair tasks over the years, but there are some key limitations. Stability concerns typically require mobile platforms to be large in order to handle far-reaching manipulators, or for the manipulators to have drastically reduced workspaces to fit onto smaller mobile platforms. Therefore we propose a combination of two widely-used robots, the Clearpath Jackal unmanned ground vehicle and the Kinova Gen3 six degree-of-freedom manipulator. The Jackal has a small footprint and works well in low-clearance indoor environments. Extensive testing of localization, navigation and mapping using LiDAR sensors makes the Jackal a well developed mobile platform suitable for mobile manipulation. The Gen3 has a long reach with reasonable power consumption for manipulation tasks. A wrist camera for RGB-D sensing and a customizable end effector interface makes the Gen3 suitable for a myriad of manipulation tasks. Typically these features would result in an unstable platform, however with a few minor hardware and software modifications, we have produced a stable, high-performance mobile manipulation platform with significant mobility, reach, sensing, and maneuverability for indoor inspection tasks, without degradation of the component robots' individual capabilities. These assertions were investigated with hardware via semi-autonomous navigation to waypoints in a busy indoor environment, and high-precision self-alignment alongside planar structures for intervention tasks.Comment: 5 pages, 7 figures, to be published in IDETC-CIE 202

Mixtures of Local Linear Subspaces for Face Recognition

Traditional subspace methods for face recognition compute a measure of similarity between images after projecting them onto a fixed linear subspace that is spanned by some principal component vectors (a.k.a. "eigenfaces") of a training set of images. By supposing a parametric Gaussian distribution over the subspace and a symmetric Gaussian noise model for the image given a point in the subspace, we can endow this framework with a probabilistic interpretation so that Bayes-optimal decisions can be made. However, we expect that different image clusters (corresponding, say, to different poses and expressions) will be best represented by different subspaces. In this paper, we study the recognition performance of a mixture of local linear subspaces model that can be fit to training data using the expectation maximization algorithm. The mixture model outperforms a nearest-neighbor classifier that operates in a PCA subspace. 1 Introduction Presented at Computer Vision and Pattern Recognitio..

MRacing: Improve Low Speed Cornering

ME450 Capstone Design and Manufacturing Experience: Fall 2020The MRacing team competes in the FSAE competition annually. In past years, MRacing vehicles have struggled in low speed cornering, specifically the Skid pad event. The aim of this project is to improve the low cornering performance of the 2021 MRacing vehicle to increase points achieved at FSAE competitions.MRacing Formula SAE, Wilson Student Team Project Centerhttp://deepblue.lib.umich.edu/bitstream/2027.42/164445/1/MRacing_Improve_Low_Speed_Cornering.pd

Assembly of DNA-Functionalized Gold Nanoparticles with Gaps and Overhangs in Linker DNA

This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry C, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jp111073wDNA-directed assembly of gold nanoparticles (AuNPs) has been extensively studied because of its important applications in analytical chemistry, materials science, and nanomedicine. In a typical system, two DNA-functionalized AuNPs are assembled via a linker DNA to form large aggregates. In the majority of the previous reports, the linker DNA is fully base paired with no gaps or overhangs present. Introducing such nonbase-paired regions in the linker DNA has been recently shown to be important for making stimuli-responsive materials and in crystallization of such AuNPs. In this work, we systematically studied the effect of introducing gaps and overhangs in the linker DNA to understand the kinetics of assembly and the melting transition of these aggregates. We found that the assembly kinetics decreased with increasing linker DNA length. The melting temperature decreased with the loss of base stacking by introducing gaps as well as the steric effect of overhangs. Additional insights were obtained by measuring the melting curves of the free DNAs in the absence of AuNPs. For example, it appeared that DNA base stacking at the nick site was favored in assembled nanoparticles compared to that in free DNA. Our results indicate that, while it is possible to form AuNP assemblies with linker DNAs containing various types of unpaired regions, these kinetic and thermodynamic factors need to be considered when designing related sensors and materials.University of Waterloo || Natural Sciences and Engineering Research Council |

Betaproteobacteria growth and nitrification rates during long-term natural dissolved organic matter decomposition experiments

As a first attempt to relate net nitrification rates with bacterial community structure in the coastal embayment of the Ría de Vigo (NW Spain), a set of 6 long-term (lasting 53 to 74 d) dissolved organic matter decomposition experiments were conducted in the dark and at a constant temperature of 15°C with surface seawater collected in January, February, April, and June 2008. Net nitrification rates were estimated from nitrate concentration changes. Evolution of bacterial community composition was followed using catalyzed reporter deposition-fluorescent in situ hybridization (CARD-FISH) and specific probes for 6 relevant bacterial groups, including Beta- and Gammaproteobacteria. The growth rates of Betaproteobacteria showed a significant linear positive relationship with nitrification rates that explained 82% of the observed variability, which strongly suggests that the main nitrifying microorganisms during the incubations belonged to the Beta subclass of Proteobacteria. A positive relationship was found between net nitrification rates and both ammonium (r2 = 0.92) and phosphate (r2 = 0.97) concentrations, which suggests a tight link among the nitrogen and phosphorus cycles, likely as a result of the role of phosphate as the bacterial growth-limiting nutrient.Peer reviewe