Gene Sets Net Correlations Analysis (GSNCA): a multivariate differential coexpression test for gene sets

Motivation: To date, Gene Set Analysis (GSA) approaches primarily focus on identifying differentially expressed gene sets (pathways). Methods for identifying differentially coexpressed pathways also exist but are mostly based on aggregated pairwise correlations, or other pairwise measures of coexpression. Instead, we propose Gene Sets Net Correlations Analysis (GSNCA), a multivariate differential coexpression test that accounts for the complete correlation structure between genes.

Results: In GSNCA, weight factors are assigned to genes in proportion to the genes' cross-correlations (intergene correlations). The problem of finding the weight vectors is formulated as an eigenvector problem with a unique solution. GSNCA tests the null hypothesis that for a gene set there is no difference in the weight vectors of the genes between two conditions. In simulation studies and the analyses of experimental data, we demonstrate that GSNCA, indeed, captures changes in the structure of genes' cross-correlations rather than differences in the averaged pairwise correlations. Thus, GSNCA infers differences in coexpression networks, however, bypassing method-dependent steps of network inference. As an additional result from GSNCA, we define hub genes as genes with the largest weights and show that these genes correspond frequently to major and specific pathway regulators, as well as to genes that are most affected by the biological difference between two conditions. In summary, GSNCA is a new approach for the analysis of differentially coexpressed pathways that also evaluates the importance of the genes in the pathways, thus providing unique information that may result in the generation of novel biological hypotheses.

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland

Strains of many infectious diseases differ in parameters that influence epidemic spread, for example virulence, transmissibility, detectability and host specificity. Knowledge of inter-strain variation can be exploited to improve management and decrease disease incidence. Bovine tuberculosis (bTB) is increasingly prevalent among farmed cattle in the UK, exerting a heavy economic burden on the farming industry and government. We aimed to determine whether strains of Mycobacterium bovis (the causative agent of bTB) identified and classified using genetic markers (spoligotyping and multi-locus VNTR analysis) varied in response to the tuberculin skin test; this being the primary method of bTB detection used in the UK. Inter-strain variation in detectability of M. bovis could have important implications for disease control. The skin test is based on a differential delayed type hypersensitivity (DTH) response to intradermal injections of purified protein derivative (PPD) from M. bovis (PPD-B) and Mycobacterium avium (PPD-A). We searched for an association between skin test response (PPD-B skin rise minus PPD-A skin rise) and M. bovis genotype at the disclosing test in culture-confirmed cases using a field dataset consisting of 21,000 isolates belonging to 63 genotypes of M. bovis from cattle in Northern Ireland. We found no substantial variation among genotypes (estimated responses clustered tightly around the mean) controlling for animal sex, breed and test effects. We also estimated the ratio of skin test detected to undetected cases (i.e. cases only detected at abattoir). The skin test detection ratio varied among abattoirs with some detecting a greater proportion of cases than others but this variation was unrelated to the community composition of genotypes within each abattoir catchment. These two lines of evidence indicate that M. bovis genotypes in Northern Ireland have similar detectability using the skin test.

A static test method to assess swivel seat strength in frontal impact

Mechanical swivel seat adaptations are a key aftermarket disability modification to any small-to medium-sized passenger vehicle. However, the crashworthiness of these devices is currently unregulated and the existing 20g dynamic sled testing approach is prohibitively expensive for prototype assessment purposes. In this paper, an alternative quasi-static test method for swivel seat assessment is presented, and two different approaches (free-body diagram and multibody modelling) validated through published experimental data are developed to determine the appropriate loading conditions to apply in the quasi-static testing.Results show the two theoretical approaches can give similar results for estimating the quasi-static loading conditions, and this depends on the seatbelt configuration. Application of the approach to quasi-static testing of both conventional seats and those with integrated seat belts showed the approach to be successful and easy to apply. It is proposed that this method be used by swivel seat designers to assess new prototypes prior to final validation via the traditional 20g sled test.

Evaluation of Corrosion Fatigue Behaviour of Laser-welded NiTi Alloys using Bending Rotation Fatigue Test in Simulated Body Fluid

Shape memory NiTi alloys have been used extensively for medical device applications such as orthopedic, dental, vascular and cardiovascular devices on account of their unique shape memory effect (SME) and super-elasticity (SE). Laser welding is found to be the most suitable method used to fabricate NiTi-based medical components. However, the performance of laser-welded NiTi alloys under corrosive environments is not fully understood and a specific focus on understanding the corrosion fatigue behaviour is not evident in the literature. This study reveals a comparison of corrosion fatigue behaviour of laser-welded and bare NiTi alloys using bending rotation fatigue (BRF) test which was integrated with a specifically designed corrosion cell. The testing environment was Hanks’ solution (simulated body fluid) at 37.5oC. Electrochemical impedance spectroscopic (EIS) measurement was carried out to monitor the change of corrosion resistance at different periods during the BRF test. Experiments indicate that the laser-welded NiTi alloy would be more susceptible to the corrosion fatigue attack than the bare NiTi alloy. This finding can serve as a benchmark for the product designers and engineers to determine the factor of safety of NiTi medical devices fabricated using laser welding.

Synergy Between an Improved Covariate Unit Root Test and Cross-sectionally Dependent Panel Data Unit Root Tests, with two Applications

This paper proposes the use of an improved covariate unit root test which exploits the cross-sectional dependence information when the panel data null hypothesis of a unit root is rejected. More explicitly, to increase the power of the test, we suggest the utilization of more than one covariate and offer several ways to select the ‘best’ covariates from the set of potential covariates represented by the individuals in the panel. Employing our methods, we investigate the Prebish-Singer hypothesis for nine commodity prices. Our results show that this hypothesis holds for all but the price of petroleum.

The Effect of the Secret Ballot on Party System Fragmentation: A Test of Three Competing Arguments

Few studies have examined the impact that the adoption of the secret ballot had on party system fragmentation outside the United States. This article tests arguments maintaining that the adoption of the secret ballot had a negative, positive or nil effect on party system fragmentation. Using time-series cross-sectional data from
several countries adopting the secret ballot around the turn of the twentieth century, the results demonstrate that the adoption of the secret ballot did not hinder – though did not favour, either – the development of multiparty systems.

Conductivity sensor technology application in steady state migration test

In this paper the current development of the steady state migration test was reviewed. Experiments were carried out for a series of concrete mixes with the steady state migration test in which conductivity sensor technology is applied. With the developed steady state migration test, conductivity in anolyte, loop current and temperature can be monitored in real time. The experimental results are conductive to understand the mechanism of chloride migration during both unsteady state and steady state. The conductivity of anolyte could be used to calculate the chloride concentration in anolyte and the theoretical correlation between them was explained. Over all, the developed steady state migration is an effective, convenient, well-defined in theory and plentiful with information method which could be used to determine the chloride diffusion coefficient of cementitious materials.

Vehicle-barrier tracking of a scaled crash test for roadside barrier design

In this paper the tracking system used to perform a scaled vehicle-barrier crash test is reported. The scaled crash test was performed as part of a wider project aimed at designing a new safety barrier making use of natural building materials. The scaled crash test was designed and performed as a proof of concept of the new mass-based safety barriers and the study was composed of two parts: the scaling technique and of a series of performed scaled crash tests. The scaling method was used for 1) setting the scaled test impact velocity so that energy dissipation and momentum transferring, from the car to the barrier, can be reproduced and 2) predicting the acceleration, velocity and displacement values occurring in the full-scale impact from the results obtained in a scaled test. To achieve this goal the vehicle and barrier displacements were to be recorded together with the vehicle accelerations and angular velocities. These quantities were measured during the tests using acceleration sensors and a tracking system. The tracking system was composed of a high speed camera and a set of targets to measure the vehicle linear and angular velocities. A code was developed to extract the target velocities from the videos and the velocities obtained were then compared with those obtained integrating the accelerations provided by the sensors to check the reliability of the method.

The performance of concrete exposed to marine environments: predictive modelling and use of laboratory/on site test methods

This paper reports an approach by which laboratory based testing and numerical modelling can be combined to predict the long term performance of a range of concretes exposed to marine environments. Firstly, a critical review of the test methods for assessing the chloride penetration resistance of concrete is given. The repeatability of the different test results is also included. In addition to the test methods, a numerical simulation model is used to explore the test data further to obtain long-term chloride ingress trends. The combined use of testing and modelling is validated with the help of long-term chloride ingress data from a North Sea exposure site. In summary, the paper outlines a methodology for determining the long term performance of concrete in marine environments.

Do mirrors reflect reality in agonistic encounters? A test of mutual cooperation in displays

Animals frequently engage in mutual displays that may allow or at least help decisions about the outcome of agonistic encounters with mutual benefit to the opponents. In fish these often involve lateral displays, with previous studies finding evidence of population-level lateralization with a marked preference for showing the right side and using the right eye. Because both opponents tend to show this preference a head to tail configuration is formed and is used extensively during the display phase. Here we tested the significance of these lateral displays by comparing displays to a mirror with those to a real opponent behind a transparent barrier. The frequency of displays was lower to a mirror but the individual displays were of greater duration indicating a slower pace of the interaction with a mirror. This suggests that fish respond to initiatives of real opponents but as mirror images do not initiate moves the focal fish only moves when it is ready to change position. However, lateralization was still found with mirrors, indicating that the right-side bias is a feature of the individual and not of the interaction between opponents. We discuss implications for ideas about the evolution of mutual cooperation and information exchange in contests, as well as the utility of the use of mirrors in the study of aggression in fish.

A proposed model membrane and test method for microneedle insertion studies

A commercial polymeric film (Parafilm M (R), a blend of a hydrocarbon wax and a polyolefin) was evaluated as a model membrane for microneedle (MN) insertion studies. Polymeric MN arrays were inserted into Parafilm M (R) (PF) and also into excised neonatal porcine skin. Parafilm M (R) was folded before the insertions to closely approximate thickness of the excised skin. Insertion depths were evaluated using optical coherence tomography (OCT) using either a force applied by a Texture Analyser or by a group of human volunteers. The obtained insertion depths were, in general, slightly lower, especially for higher forces, for PF than for skin. However, this difference was not a large, being less than the 10% of the needle length. Therefore, all these data indicate that this model membrane could be a good alternative to biological tissue for MN insertion studies. As an alternative method to OCT, light microscopy was used to evaluate the insertion depths of MN in the model membrane. This provided a rapid, simple method to compare different MN formulations. The use of Parafilm M (R), in conjunction with a standardised force/time profile applied by a Texture Analyser, could provide the basis for a rapid MN quality control test suitable for in-process use. It could also be used as a comparative test of insertion efficiency between candidate MN formulations. 

A research-based approach to exploring the adoption of novel UK-based concrete test methods in Chinese construction sector

As part of a UK-China science bridge project - a UK government funded initiative linking leading universities and businesses in selective partnering countries in 2009 a collaborative research programme was initiated between Queen's University and the Research Institute of High Performance Concrete (part of the Central Research Institute of Building and Construction) in Beijing.

For further details email b.magee@ulster.ac.uk

The BTA stat test:A tumor marker for the detection of upper tract transitional cell carcinoma

Objectives. To conduct a prospective evaluation to determine the utility of the BTA stat test in the detection of upper tract transitional cell carcinoma (UTTCC). Monitoring for UTTCC currently relies on invasive procedures such as upper tract imaging, ureteral washing cytology (UWC) and/or ureteroscopy, or voided urine cytology (VUC). The BTA stat test is a sensitive qualitative immunoassay that detects human complement factor H-related protein in voided urine.

Methods. A total of 81 patients participated, 27 with histopathologically confirmed UTTCC, 26 with upper tract calculi, and 28 with microscopic hematuria but no evidence of urologic disease. Voided specimens collected before surgery or treatment were tested with the BTA stat test and VUC. UWC was performed in specimens collected by a ureteral catheter.

Results. The BTA stat test was significantly more sensitive and specific than VUC or UWC. The overall sensitivity for each was 82%, 11%, and 48%; the specificity was 89%, 54%, and 33%. The positive predictive value for the BTA stat test was 79% and the negative predictive value was 91%, both the highest of the three tests.

Conclusions. The BTA stat test was superior to VUC and UWC in the detection of UTTCC. These results may support the adoption of a less aggressive follow-up policy when monitoring for UTTCC when the BTA stat result is negative. If cystoscopy is negative and the BTA stat test is positive, upper tract investigations should be expedited and, if the bladder is in place, bladder biopsies performed. (C) 2001, Elsevier Science Inc.