Observations of Trip Generation, Route Choice, and Trip Chaining with Private-Sector Probe Vehicle GPS Data

This paper presents an exploratory study of GPS data from a private-sector data provider for analysis of trip generation, route choice, and trip chaining. The study focuses on travel to and from the Indianapolis International Airport. GPS data consisting of nearly 1 billion waypoints for 12 million trips collected over a 6-week period in the state of Indiana. Within this data, there were approximately 10,000 trip records indicating travel to facilities associated with the Indianapolis airport. The analysis is based the matching of waypoints to geographic areas that define the extents of roadways and various destinations. A regional analysis of trip ends finds that travel demand for passenger services at the airport extends across a region spanning about 950 km. Local travel between land uses near the airport is examined by generation of an origin-destination matrix, and route choice between the airport and downtown Indianapolis is studied. Finally, the individual trips are scanned to identify trip chaining behavior. Several observations are made regarding these dynamics from the data. There is some sample bias (types of vehicles) and opportunities to further refine some of the land use definitions, but the study results suggest this type of data will provide a new frontier for characterizing travel demand patterns at a variety of scales

Book Reviews

Creating a Local History Archive at Your Public Library. Faye Phillips. Paper Cadavers: The Archives of Dictatorship in Guatemala. Kirsten Weld. The Silence of the Archives. David Thomas, Simon Fowler, and Valerie Johnson. The Bad-Ass Librarians of Timbuktu and Their Race to Save the World\u27s Most Precious Manuscripts. Joshua Hammer. The International Business Archives Handbook: Understanding and Managing the Historical Records of Business. Edited by Alison Turton. Putting Descriptive Standards to Work. Edited by Kris Kiesling and Christopher J. Prom. Moving Image and Sound Collections for Archivists. Anthony Cocciolo

Enhancement of Adeno-Associated Virus-Mediated Gene Therapy Using Hydroxychloroquine in Murine and Human Tissues.

The therapeutic effects of gene therapy using adeno-associated virus (AAV) vectors are dependent on the efficacy of viral transduction. Currently, we have reached the safe limits of AAV vector dose, beyond which damaging inflammatory responses are seen. To improve the efficacy of AAV transduction, we treated mouse embryonic fibroblasts, primate retinal pigment epithelial cells, and human retinal explants with hydroxychloroquine (HCQ) 1 h prior to transduction with an AAV2 vector encoding GFP driven by a ubiquitous CAG promoter. This led to a consistent increase in GFP expression, up to 3-fold, compared with vector alone. Comparing subretinal injections of AAV2.CAG.GFP vector alone versus co-injection with 18.75 μM HCQ in paired eyes in mice, mean GFP expression was 4.6-fold higher in retinae co-treated with HCQ without retinal toxicity. A comparative 5.9-fold effect was seen with an AAV8(Y733F).GRK1.GFP vector containing the photoreceptor-specific rhodopsin kinase promoter. While the mechanism of action remains to be fully elucidated, our data suggest that a single pulse of adjunctive HCQ could safely improve AAV transduction in vivo, thus providing a novel strategy for enhancing the clinical effects of gene therapy

Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit

Notum is a carboxylesterase that suppresses Wnt signaling through deacylation of an essential palmitoleate group on Wnt proteins. There is a growing understanding of the role Notum plays in human diseases such as colorectal cancer and Alzheimer's disease, supporting the need to discover improved inhibitors, especially for use in models of neurodegeneration. Here, we have described the discovery and profile of 8l (ARUK3001185) as a potent, selective, and brain-penetrant inhibitor of Notum activity suitable for oral dosing in rodent models of disease. Crystallographic fragment screening of the Diamond-SGC Poised Library for binding to Notum, supported by a biochemical enzyme assay to rank inhibition activity, identified 6a and 6b as a pair of outstanding hits. Fragment development of 6 delivered 8l that restored Wnt signaling in the presence of Notum in a cell-based reporter assay. Assessment in pharmacology screens showed 8l to be selective against serine hydrolases, kinases, and drug targets

Camilla: A Centaur reconnaissance and impact mission concept

Centaurs, minor planets with a semi-major axis between the orbits of Jupiter and Neptune (5–30 AU), are thought to be among the most diverse small bodies in the solar system. These important targets for future missions may have recently been Kuiper Belt Objects (KBOs), which are thought to be chemically and physically primitive remnants of the early solar system. While the Kuiper Belt spans distances of 30–50 AU, making direct observations difficult, Centaurs' proximity to the Earth and Sun make them more accessible targets for robotic missions. Thus, we outline a mission concept designed to reconnoiter 10199 Chariklo, the largest Centaur and smallest ringed body yet discovered. Named for a legendary Centaur tamer, the conceptual Camilla mission is designed to fit under the cost cap of the National Aeronautics and Space Administration (NASA) New Frontiers program, leveraging a conservative payload to support a foundational scientific investigation to these primitive bodies. Specifically, the single flyby encounter utilizes a combined high-resolution camera/VIS-IR mapping spectrometer, a sub-mm point spectrometer, and a UV mapping spectrometer. In addition, the mission concept utilizes a kinetic impactor, which would provide the first opportunity to sample the composition of potentially primitive subsurface material beyond Saturn, thus providing key insights into solar system origins. Such a flyby of the Chariklo system would provide a linchpin in the understanding of small body composition, evolution, and transport of materials in the solar system