Integrating planning and environmental protection : an analysis of post-Brexit regulatory styles and practitioner attitudes in the UK

Acknowledgements: We are grateful for the support of the Royal Town Planning Institute, who commissioned the research on which this paper is based, and to the reviewers and editors from Planning Theory and Practice for their helpful comments on an earlier version of the paper.Peer reviewedPostprin

Identification and utilization of arbitrary correlations in models of recombination signal sequences

BACKGROUND: A significant challenge in bioinformatics is to develop methods for detecting and modeling patterns in variable DNA sequence sites, such as protein-binding sites in regulatory DNA. Current approaches sometimes perform poorly when positions in the site do not independently affect protein binding. We developed a statistical technique for modeling the correlation structure in variable DNA sequence sites. The method places no restrictions on the number of correlated positions or on their spatial relationship within the site. No prior empirical evidence for the correlation structure is necessary. RESULTS: We applied our method to the recombination signal sequences (RSS) that direct assembly of B-cell and T-cell antigen-receptor genes via V(D)J recombination. The technique is based on model selection by cross-validation and produces models that allow computation of an information score for any signal-length sequence. We also modeled RSS using order zero and order one Markov chains. The scores from all models are highly correlated with measured recombination efficiencies, but the models arising from our technique are better than the Markov models at discriminating RSS from non-RSS. CONCLUSIONS: Our model-development procedure produces models that estimate well the recombinogenic potential of RSS and are better at RSS recognition than the order zero and order one Markov models. Our models are, therefore, valuable for studying the regulation of both physiologic and aberrant V(D)J recombination. The approach could be equally powerful for the study of promoter and enhancer elements, splice sites, and other DNA regulatory sites that are highly variable at the level of individual nucleotide positions

Prospective Estimation of Recombination Signal Efficiency and Identification of Functional Cryptic Signals in the Genome by Statistical Modeling

The recombination signals (RS) that guide V(D)J recombination are phylogenetically conserved but retain a surprising degree of sequence variability, especially in the nonamer and spacer. To characterize RS variability, we computed the position-wise information, a measure correlated with sequence conservation, for each nucleotide position in an RS alignment and demonstrate that most position-wise information is present in the RS heptamers and nonamers. We have previously demonstrated significant correlations between RS positions and here show that statistical models of the correlation structure that underlies RS variability efficiently identify physiologic and cryptic RS and accurately predict the recombination efficiencies of natural and synthetic RS. In scans of mouse and human genomes, these models identify a highly conserved family of repetitive DNA as an unexpected source of frequent, cryptic RS that rearrange both in extrachromosomal substrates and in their genomic context

Generation of Ultrasound Pulses in Water Using Granular Chains with a Finite Matching Layer

Wave propagation in granular chains is subject to dispersive effects as well as nonlinear effects arising from the Hertzian contact law. This enables the formation of wideband pulses, which is a desirable feature in the context of diagnostic and therapeutic ultrasound applications. However, coupling of the ultrasonic energy from a chain of spheres into biological tissue is a big challenge. In order to improve the energy transfer efficiency into biological materials, a matching layer is required. A prototype device is designed to address this by using six aluminum spheres and a vitreous carbon matching layer. The matching layer and the precompression force are selected specifically to maximize the acoustic pressure in water and its bandwidth. The designed device generates a train of wideband ultrasonic pulses from a narrow-band input with a center frequency of 73 kHz. An analytical model is created to simulate the behavior of a matching layer as a flexible thin plate clamped from the edges. This m odel is then verified using free-field hydrophone measurements in water, which successfully predict the increased bandwidth by generation of harmonics. The shapes of the measured and predicted waveforms are compared by calculating the normalized cross-correlation, which shows 83% similarity between both. Since the generation of harmonics is of interest in this study, the total harmonic distortion (THD) and the -6-dB bandwidth of the signals are used to analyze signal fidelity between the hydrophone measurements and the model predictions. The acoustic signals in water have a root-mean-square THD of 73%, and the model predicts a root-mean-square THD of 78%. The -6-dB bandwidths of individual pulses measured by a hydrophone and predicted with the model are 280 and 252 kHz, respectively. At these high ultrasonic frequencies, it is an experimental demonstration of resonant chains operating in water with a matching layer

VO: Vaccine Ontology

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced vaccine data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO, "http://www.violinet.org/vaccineontology":http://www.violinet.org/vaccineontology) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented.
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