Fine-grained traffic state estimation and visualisation

Tools for visualising the current traffic state are used by local authorities for strategic monitoring of the traffic network and by everyday users for planning their journey. Popular visualisations include those provided by Google Maps and by Inrix. Both employ a traffic lights colour-coding system, where roads on a map are coloured green if traffic is flowing normally and red or black if there is congestion. New sensor technology, especially from wireless sources, is allowing resolution down to lane level. A case study is reported in which a traffic micro-simulation test bed is used to generate high-resolution estimates. An interactive visualisation of the fine-grained traffic state is presented. The visualisation is demonstrated using Google Earth and affords the user a detailed three-dimensional view of the traffic state down to lane level in real time

History of a pummelled landscape

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Defining probability-based rail station catchments for demand modelling

The aggregate models commonly used in the UK to estimate demand for new local rail stations require the station catchment to be defined first, so that inputs into the model, such as the population from which demand will be generated, can be specified. The methods typically used to define the catchment implicitly assume that station choice is a deterministic process, and that stations exist in isolation from each other. However, studies show that pre-defined catchments account for only 50-60 percent of observed trips, choice of station is not homogeneous within zones, catchments overlap, and catchments vary by access mode and station type. This paper describes early work to implement an alternative probability-based approach, through the development of a station choice prediction model. To derive realistic station access journey explanatory variables, a routable multi-modal network, incorporating data from OpenStreetMap, the Traveline National Data Set and National Rail timetable, was built using OpenTripPlanner and queried using an API wrapper developed in R. Results from a series of multinomial logit models are presented and a method for generating probabilistic catchments using estimated parameter values is described. An example probabilistic catchment is found to provide a realistic representation of the observed catchment, and to perform better than deterministic catchments

The future is now: single-cell genomics of bacteria and archaea

Interest in the expanding catalog of uncultivated microorganisms, increasing recognition of heterogeneity among seemingly similar cells, and technological advances in whole-genome amplification and single-cell manipulation are driving considerable progress in single-cell genomics. Here, the spectrum of applications for single-cell genomics, key advances in the development of the field, and emerging methodology for single-cell genome sequencing are reviewed by example with attention to the diversity of approaches and their unique characteristics. Experimental strategies transcending specific methodologies are identified and organized as a road map for future studies in single-cell genomics of environmental microorganisms. Over the next decade, increasingly powerful tools for single-cell genome sequencing and analysis will play key roles in accessing the genomes of uncultivated organisms, determining the basis of microbial community functions, and fundamental aspects of microbial population biology.National Institutes of Health (U.S.) (R01 HG004863)Burroughs Wellcome Fun

Simple Bulk Readout of Digital Nucleic Acid Quantification Assays

Digital assays are powerful methods that enable detection of rare cells and counting of individual nucleic acid molecules. However, digital assays are still not routinely applied, due to the cost and specific equipment associated with commercially available methods. Here we present a simplified method for readout of digital droplet assays using a conventional real-time PCR instrument to measure bulk fluorescence of droplet-based digital assays. We characterize the performance of the bulk readout assay using synthetic droplet mixtures and a droplet digital multiple displacement amplification (MDA) assay. Quantitative MDA particularly benefits from a digital reaction format, but our new method applies to any digital assay. For established digital assay protocols such as digital PCR, this method serves to speed up and simplify assay readout. Our bulk readout methodology brings the advantages of partitioned assays without the need for specialized readout instrumentation. The principal limitations of the bulk readout methodology are reduced dynamic range compared with droplet-counting platforms and the need for a standard sample, although the requirements for this standard are less demanding than for a conventional real-time experiment. Quantitative whole genome amplification (WGA) is used to test for contaminants in WGA reactions and is the most sensitive way to detect the presence of DNA fragments with unknown sequences, giving the method great promise in diverse application areas including pharmaceutical quality control and astrobiology.Burroughs Wellcome Fund (Career Award at the Scientific Interface

Targeting individual cells by barcode in pooled sequence libraries

Transcriptional profiling of thousands of single cells in parallel by RNA-seq is now routine. However, due to reliance on pooled library preparation, targeting analysis to particular cells of interest is difficult. Here, we present a multiplexed PCR method for targeted sequencing of select cells from pooled single-cell sequence libraries. We demonstrated this molecular enrichment method on multiple cell types within pooled single-cell RNA-seq libraries produced from primary human blood cells. We show how molecular enrichment can be combined with FACS to efficiently target ultra-rare cell types, such as the recently identified AXL+SIGLEC6+ dendritic cell (AS DC) subset, in order to reduce the required sequencing effort to profile single cells by 100-fold. Our results demonstrate that DNA barcodes identifying cells within pooled sequencing libraries can be used as targets to enrich for specific molecules of interest, for example reads from a set of target cells.National Institute of Allergy and Infectious Diseases (U.S.) (U24AI11866803)National Human Genome Research Institute (U.S.) (RM1HG00619307)Broad Institute of MIT and HarvardBurroughs Wellcome Fund (Career Award at the Scientific Interface)National Science Foundation (U.S.). Graduate Research FellowshipNational Human Genome Research Institute (U.S.). Centers of Excellence in Genomic Science (RM1HG00619307)Massachusetts Institute of Technolog

Does organisational heritage matter in the development of offshore markets? the case of Australian life insurers

The globalization of financial markets over the past decade has focused the spotlight on the responsiveness of financial firms to international pressures. Insurance markets have traditionally relied on global networks not only to expand the insurers\u27 sphere of influence but also to support domestic business. Until relatively recently, Australian insurance companies have not played a significant role in the development of international markets. However, in the last decade of the twentieth century Australian insurers ventured overseas on a scale without precedence. This article presents an historical perspective on the internationalization of the Australian life-insurance market with a view to understanding why these firms have been classified "late starters" in the internationalization stakes. In a broader capacity it provides insights into the impediments to overseas expansion and the forces encouraging or discouraging the development of cross border networks

Sampling distributions and the bootstrap

The bootstrap can be used to assess uncertainty of sample estimates

Combinatorial drug discovery in nanoliter droplets

Combinatorial drug treatment strategies perturb biological networks synergistically to achieve therapeutic effects and represent major opportunities to develop advanced treatments across a variety of human disease areas. However, the discovery of new combinatorial treatments is challenged by the sheer scale of combinatorial chemical space. Here, we report a high-throughput system for nanoliter-scale phenotypic screening that formulates a chemical library in nanoliter droplet emulsions and automates the construction of chemical combinations en masse using parallel droplet processing. We applied this system to predict synergy between more than 4,000 investigational and approved drugs and a panel of 10 antibiotics against Escherichia coli, a model gram-negative pathogen. We found a range of drugs not previously indicated for infectious disease that synergize with antibiotics. Our validated hits include drugs that synergize with the antibiotics vancomycin, erythromycin, and novobiocin, which are used against gram-positive bacteria but are not effective by themselves to resolve gram-negative infections. Keywords: high-throughput screening; nanoliter droplet; drug synergy; antibiotics; small molecule