The cooling steam of the Polar Express : historical origins, properties and implications of performance capture

As the first academically rigorous interrogation of the generation of performance within the global frame of the motion capture volume, this research presents a historical contextualisation and develops and tests a set of first principles through an original series of theoretically informed, practical exercises to guide those working in the emergent space of performance capture. It contributes a new understanding of the framing of performance in The Omniscient Frame, and initiates and positions performance capture as a new and distinct interdisciplinary discourse in the fields of theatre, animation, performance studies and film.

Combining passive sampling and toxicity testing for evaluation of mixtures of polar organic chemicals in sewage treatment plant effluent

Effluent from sewage treatment plants has been associated with a range of pollutant effects. Depending on the influent composition and treatment processes the effluent may contain a myriad of different chemicals which makes monitoring very complex. In this study we aimed to monitor relatively polar organic pollutant mixtures using a combination of passive sampling techniques and a set of biochemistry based assays covering acute bacterial toxicity (Microtox™), phytotoxicity (Max-I-PAM assay) and genotoxicity (umuC assay). The study showed that all of the assays were able to detect effects in the samples and allowed a comparison of the two plants as well as a comparison between the two sampling periods. Distinct improvements in water quality were observed in one of the plants as result of an upgrade to a UV disinfection system, which improved from 24× sample enrichment required to induce a 50% response in the Microtox™ assay to 84×, from 30× sample enrichment to induce a 50% reduction in photosynthetic yield to 125×, and the genotoxicity observed in the first sampling period was eliminated. Thus we propose that biochemical assay techniques in combination with time integrated passive sampling can substantially contribute to the monitoring of polar organic toxicants in STP effluents.

Insertions in the OCL1 locus of Acinetobacter baumannii lead to shortened lipooligosaccharides

Genomes of 82 Acinetobacter baumannii global clones 1 (GC1) and 2 (GC2) isolates were sequenced and different forms of the locus predicted to direct synthesis of the outer core (OC) of the lipooligosaccharide were identified. OCL1 was in all GC2 genomes, whereas GC1 isolates carried OCL1, OCL3 or a new locus, OCL5. Three mutants in which an insertion sequence (ISAba1 or ISAba23) interrupted OCL1 were identified. Isolates with OCL1 intact produced only lipooligosaccharide, while the mutants produced lipooligosaccharide of reduced molecular weight. Thus, the assignment of the OC locus as that responsible for the synthesis of the OC is correct.

Variation in the OC locus of Acinetobacter baumannii genomes predicts extensive structural diversity in the Lipooligosaccharide

Lipooligosaccharide (LOS) is a complex surface structure that is linked to many pathogenic properties of Acinetobacter baumannii. In A. baumannii, the genes responsible for the synthesis of the outer core (OC) component of the LOS are located between ilvE and aspS. The content of the OC locus is usually variable within a species, and examination of 6 complete and 227 draft A. baumannii genome sequences available in GenBank non-redundant and Whole Genome Shotgun databases revealed nine distinct new types, OCL4-OCL12, in addition to the three known ones. The twelve gene clusters fell into two distinct groups, designated Group A and Group B, based on similarities in the genes present. OCL6 (Group B) was unique in that it included genes for the synthesis of L-Rhamnosep. Genetic exchange of the different configurations between strains has occurred as some OC forms were found in several different sequence types (STs). OCL1 (Group A) was the most widely distributed being present in 18 STs, and OCL6 was found in 16 STs. Variation within clones was also observed, with more than one OC locus type found in the two globally disseminated clones, GC1 and GC2, that include the majority of multiply antibiotic resistant isolates. OCL1 was the most abundant gene cluster in both GC1 and GC2 genomes but GC1 isolates also carried OCL2, OCL3 or OCL5, and OCL3 was also present in GC2. As replacement of the OC locus in the major global clones indicates the presence of sub-lineages, a PCR typing scheme was developed to rapidly distinguish Group A and Group B types, and to distinguish the specific forms found in GC1 and GC2 isolates.

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

Investigating the population structure of Queensland invasive Streptococcus pneumoniae isolates in children: Using a modified multi-locus variable number of tandem repeat analysis and a novel minimum SNPs capsular typing method

This research investigated the use of DNA fingerprinting to characterise the bacteria Streptococcus pneumoniae or pneumococcus, and hence gain insight into the development of new vaccines or antibiotics. Different bacterial DNA fingerprinting methods were studied, and a novel method was developed and validated, which characterises different cell coatings that pneumococci produce. This method was used to study the epidemiology of pneumococci in Queensland before and after the introduction of the current pneumococcal vaccine. This study demonstrated that pneumococcal disease is highly prevalent in children under four years, that the bacteria can `switch' its cell coating to evade the vaccine, and that some DNA fingerprinting methods are more discriminatory than others. This has an impact on understanding which strains are more prone to cause invasive disease. Evidence of the excellent research findings have been published in high impact internationally refereed journals.

The interleukin 1 gene cluster contains a major susceptibility locus for ankylosing spondylitis

Ankylosing spondylitis (AS) is a common and highly heritable inflammatory arthropathy. Although the gene HLA-B27 is almost essential for the inheritance of the condition, it alone is not sufficient to explain the pattern of familial recurrence of the disease. We have previously demonstrated suggestive linkage of AS to chromosome 2q13, a region containing the interleukin 1 (IL-1) family gene cluster, which includes several strong candidates for involvement in the disease. In the current study, we describe strong association and transmission of IL-1 family gene cluster single-nucleotide polymorphisms and haplotypes with AS.

Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5×10-8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10-8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98-1.14; p=0.17), displaying high degree of heterogeneity (I2=57%; Qhet p=0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.

The root locus method: application to linear stability analysis and design of cooperative car-following models

A global framework for linear stability analyses of traffic models, based on the dispersion relation root locus method, is presented and is applied taking the example of a broad class of car-following (CF) models. This approach is able to analyse all aspects of the dynamics: long waves and short wave behaviours, phase velocities and stability features. The methodology is applied to investigate the potential benefits of connected vehicles, i.e. V2V communication enabling a vehicle to send and receive information to and from surrounding vehicles. We choose to focus on the design of the coefficients of cooperation which weights the information from downstream vehicles. The coefficients tuning is performed and different ways of implementing an efficient cooperative strategy are discussed. Hence, this paper brings design methods in order to obtain robust stability of traffic models, with application on cooperative CF models

Evaluation of the relationship between Chlamydia pecorum sequence types and disease using a species-specific multi-locus sequence typing scheme (MLST)

Chlamydia pecorum is globally associated with several ovine diseases including keratoconjunctivitis and polyarthritis. The exact relationship between the variety of C. pecorum strains reported and the diseases described in sheep remains unclear, challenging efforts to accurately diagnose and manage infected flocks. In the present study, we applied C. pecorum multi-locus sequence typing (MLST) to C. pecorum positive samples collected from sympatric flocks of Australian sheep presenting with conjunctivitis, conjunctivitis with polyarthritis, or polyarthritis only and with no clinical disease (NCD) in order to elucidate the exact relationships between the infecting strains and the range of diseases. Using Bayesian phylogenetic and cluster analyses on 62 C. pecorum positive ocular, vaginal and rectal swab samples from sheep presenting with a range of diseases and in a comparison to C. pecorum sequence types (STs) from other hosts, one ST (ST 23) was recognised as a globally distributed strain associated with ovine and bovine diseases such as polyarthritis and encephalomyelitis. A second ST (ST 69) presently only described in Australian animals, was detected in association with ovine as well as koala chlamydial infections. The majority of vaginal and rectal C. pecorum STs from animals with NCD and/or anatomical sites with no clinical signs of disease in diseased animals, clustered together in a separate group, by both analyses. Furthermore, 8/13 detected STs were novel. This study provides a platform for strain selection for further research into the pathogenic potential of C. pecorum in animals and highlights targets for potential strain-specific diagnostic test development.

Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10-8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's Esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved.

Genome-wide study of familial juvenile hyperuricaemic (gouty) nephropathy (FJHN) indicates a new locus, FJHN3, linked to chromosome 2p22.1-p21

Familial juvenile hyperuricaemic (gouty) nephropathy (FJHN), is an autosomal dominant disease associated with a reduced fractional excretion of urate, and progressive renal failure. FJHN is genetically heterogeneous and due to mutations of three genes: uromodulin (UMOD), renin (REN) and hepatocyte nuclear factor-1beta (HNF-1β) on chromosomes 16p12, 1q32.1, and 17q12, respectively. However, UMOD, REN or HNF-1β mutations are found in only ~45% of FJHN probands, indicating the involvement of other genetic loci in ~55% of probands. To identify other FJHN loci, we performed a single nucleotide polymorphism (SNP)-based genome-wide linkage analysis, in six FJHN families in whom UMOD, HNF-1β and REN mutations had been excluded. Parametric linkage analysis using a 'rare dominant' model established linkage in five of the six FJHN families, with a LOD score >+3, at 0% recombination, between FJHN and SNPs at chromosome 2p22.1-p21. Analysis of individual recombinants in two unrelated affected individuals defined a ~5.5 Mbp interval, flanked telomerically by SNP RS372139 and centromerically by RS896986 that contained the locus, designated FJHN3. The interval contains 28 genes, and DNA sequence analysis of the most likely candidate, solute carrier family 8 member 1 (SLC8A1), did not identify any abnormalities in the FJHN3 probands. FJHN3 is likely located within a ~5.5 Mbp interval on chromosome 2p22.1-p21, and identifying the genetic abnormality will help to further elucidate mechanisms predisposing to gout and renal failure.