Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand

Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.

A unique isolate of beak and feather disease virus isolated from budgerigars (Melopsittacus undulatus) in South Africa

Beak and feather disease virus (BFDV), the causative agent of psittacine beak and feather disease (PBFD) infects psittaciformes worldwide. We provide an annotated sequence record of three full-length unique genomes of BFDV isolates from budgerigars (Melopsittacus undulatus) from a breeding farm in South Africa. The isolates share >99% nucleotide sequence identity with each other and ~96% nucleotide sequence identity to two recent isolates (Melopsittacus undulatus) from Thailand but only between 91. 6 and 86. 6% identity with all other full-length BFDV sequences. Maximum-likelihood analysis and recombination analysis suggest that the South African budgerigar BFDV isolates are unique to budgerigars, are non-recombinant in origin, and represent a new genotype of BFDV. © 2010 Springer-Verlag.

Critical timescales and time intervals for coupled linear processes

In 1991, McNabb introduced the concept of mean action time (MAT) as a finite measure of the time required for a diffusive process to effectively reach steady state. Although this concept was initially adopted by others within the Australian and New Zealand applied mathematics community, it appears to have had little use outside this region until very recently, when in 2010 Berezhkovskii and coworkers rediscovered the concept of MAT in their study of morphogen gradient formation. All previous work in this area has been limited to studying single–species differential equations, such as the linear advection–diffusion–reaction equation. Here we generalise the concept of MAT by showing how the theory can be applied to coupled linear processes. We begin by studying coupled ordinary differential equations and extend our approach to coupled partial differential equations. Our new results have broad applications including the analysis of models describing coupled chemical decay and cell differentiation processes, amongst others.

Public, private, or hybrid? What the upstream oil and gas industry can learn from other sectors about ‘the cloud’

Despite the compelling case for moving towards cloud computing, the upstream oil & gas industry faces several technical challenges—most notably, a pronounced emphasis on data security, a reliance on extremely large data sets, and significant legacy investments in information technology (IT) infrastructure—that make a full migration to the public cloud difficult at present. Private and hybrid cloud solutions have consequently emerged within the industry to yield as much benefit from cloud-based technologies as possible while working within these constraints. This paper argues, however, that the move to private and hybrid clouds will very likely prove only to be a temporary stepping stone in the industry’s technological evolution. By presenting evidence from other market sectors that have faced similar challenges in their journey to the cloud, we propose that enabling technologies and conditions will probably fall into place in a way that makes the public cloud a far more attractive option for the upstream oil & gas industry in the years ahead. The paper concludes with a discussion about the implications of this projected shift towards the public cloud, and calls for more of the industry’s services to be offered through cloud-based “apps.”

Chlamydia pneumoniae : modern insights into an ancient pathogen

Chlamydia pneumoniae is an enigmatic human and animal pathogen. Originally discovered in association with acute human respiratory disease, it is now associated with a remarkably wide range of chronic diseases as well as having a cosmopolitan distribution within the animal kingdom. Molecular typing studies suggest that animal strains are ancestral to human strains and that C. pneumoniae crossed from animals to humans as the result of at least one relatively recent zoonotic event. Whole genome analyses appear to support this concept – the human strains are highly conserved whereas the single animal strain that has been fully sequenced has a larger genome with several notable differences. When compared to the other, better known chlamydial species that is implicated in human infection, Chlamydia trachomatis, C. pneumoniae demonstrates pertinent differences in its cell biology, development, and genome structure. Here, we examine the characteristic facets of C. pneumoniae biology, offering insights into the diversity and evolution of this silent and ancient pathogen.

Comparison of antigen detection and quantitative PCR in the detection of chlamydial infection in koalas (Phascolarctos cinereus)

The gold standard method for detecting chlamydial infection in domestic and wild animals is PCR, but the technique is not suited to testing animals in the field when a rapid diagnosis is frequently required. The objective of this study was to compare the results of a commercially available enzyme immunoassay test for Chlamydia against a quantitative Chlamydia pecorum-specific PCR performed on swabs collected from the conjunctival sac, nasal cavity and urogenital sinuses of naturally infected koalas (Phascolarctos cinereus). The level of agreement for positive results between the two assays was low (43.2%). The immunoassay detection cut-off was determined as approximately 400 C. pecorum copies, indicating that the test was sufficiently sensitive to be used for the rapid diagnosis of active chlamydial infections.

Antigenic specificity of a monovalent versus polyvalent MOMP based Chlamydia pecorum vaccine in koalas (Phascolarctos cinereus)

Chlamydia continues to be a major pathogen of koalas. The bacterium is associated with ocular, respiratory and urogenital tract infections and a vaccine is considered the best option to limit the decline of mainland koala populations. Over the last 20 years, efforts to develop a chlamydial vaccine in humans have focussed on the use of the chlamydial major outer membrane protein (MOMP). Potential problems with the use of MOMP-based vaccines relate to the wide range of genetic diversity in its four variable domains. In the present study, we evaluated the immune response of koalas vaccinated with a MOMP-based C. pecorum vaccine formulated with genetically and serologically diverse MOMPs. Animals immunised with individual MOMPs developed strong antibody and lymphocyte proliferation responses to both homologous as well as heterologous MOMP proteins. Importantly, we also showed that vaccine induced antibodies which effectively neutralised various heterologous strains of koala C. pecorum in an in vitro assay. Finally, we also demonstrated that the immune responses in monovalent as well as polyvalent MOMP vaccine groups were able to recognise whole chlamydial elementary bodies, illustrating the feasibility of developing an effective MOMP based C. pecorum vaccine that could protect against a range of strains.

Orthopaedics and Trauma Queensland Annual Report 2011

Orthopaedics and Trauma Queensland, a Centre for Research and Education in Musculoskeletal Disorders, is an internationally recognised research group that is developing into an international leader in research and education. It provides a stimulus for research, education and clinical application within the international orthopaedic and trauma communities. Orthopaedics and Trauma Queensland develops and promotes the innovative use of engineering and technology, in collaboration with surgeons, to provide new techniques, materials, procedures and medical devices. Its integration with clinical practice and strong links with hospitals ensure that the research will be translated into practical outcomes for patients. The group undertakes clinical practice in orthopaedics and trauma and applies core engineering skills to challenges in medicine. The research is built on a strong foundation of knowledge in biomedical engineering, and incorporates expertise in cell biology, mathematical modelling, human anatomy and physiology and clinical medicine in orthopaedics and trauma. New knowledge is being developed and applied to the full range of orthopaedic diseases and injuries, such as knee and hip replacements, fractures and spinal deformities.

Teamworking for security : the collaborative approach

Collaborative methods are promising tools for solving complex security tasks. In this context, the authors present the security overlay framework CIMD (Collaborative Intrusion and Malware Detection), enabling participants to state objectives and interests for joint intrusion detection and find groups for the exchange of security-related data such as monitoring or detection results accordingly; to these groups the authors refer as detection groups. First, the authors present and discuss a tree-oriented taxonomy for the representation of nodes within the collaboration model. Second, they introduce and evaluate an algorithm for the formation of detection groups. After conducting a vulnerability analysis of the system, the authors demonstrate the validity of CIMD by examining two different scenarios inspired sociology where the collaboration is advantageous compared to the non-collaborative approach. They evaluate the benefit of CIMD by simulation in a novel packet-level simulation environment called NeSSi (Network Security Simulator) and give a probabilistic analysis for the scenarios.

Polycaprolactone-based scaffold plus recombinant human bone morphogenic protein rhBMP-2) in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. The resulting spinal deformity consists of coronal curvature, hypokyphosis of the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral (IV) discs have been surgically cleared and the disc spaces filled with graft material. Recently a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone has been developed for bone regeneration at load bearing sites. Combined with rhBMP-2, this has been shown to be successful in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft alone. The study aimed to establish a large animal thoracic spine interbody fusion model, develop spine biodegradable scaffolds (PCL) in combination with biologics (rhBMP-2) and to establish a platform for research into spine tissue engineering constructs. Preliminary results demonstrate higher grades of radiologically evident bony fusion across all levels when comparing fusion scores between the 3 and 6 month postop groups at the PCL CaP coated scaffold level, which is observed to be a similar grade to autograft, while no fusion is seen at the scaffold only level. Results to date suggest that the combination of rhBMP-2 and scaffold engineering actively promotes bone formation, laying the basis of a viable tissue engineered constructs.

Intrapleural analgesis following endoscopic scoliosis correction

Endoscopic scoliosis correction plays an important part in the surgical options available for treating adolescent idiopathic scoliosis. However, there is a paucity of literature examining optimum methods of analgesia following this type of surgery. The role of intrapleural analgesia is examined and described. In this study, local anaesthetic administration via an intrapleural catheter was found to be a safe and effective method of analgesia following endoscopic scoliosis correction. Post-operative pain following anterior scoliosis correction can be reduced to ‘mild’ levels by combined analgesia regimes. Surgeons may wish to expand its use into open or minimally invasive anterior scoliosis correction or anterior releases.

Biomechanical performance of polycaprolactone (PCL)-based scaffold with rhBMP-2 in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. Resulting spine deformities include progressive coronal curvature, hypokyphosis, or frank lordosis in the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral discs have been surgically cleared and the disc spaces filled with graft material. Problems with bone graft harvest site morbidity as well as limited bone availability have led to the search for bone graft substitutes. Recently, a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone (PCL) has been developed for bone regeneration at load bearing sites. Combined with recombinant human bone morphogenic protein–2 (rhBMP-2), this has been shown to be successful in acting as a bone graft substitute in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft. This in vivo sheep study intends to evaluate the suitability of a custom designed medical grade PCL scaffold in combination with rhBMP-2 as a bone graft substitute in the setting of mini–thoracotomy surgery as a platform for ongoing research to benefit patients with adolescent idiopathic scoliosis.

Patient-specific simulations of spinal deformity surgery

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity involving the side-to-side curvature of the spine in the coronal plane and axial rotation of the vertebrae in the transverse plane. For patients with a severe or rapidly progressing deformity, corrective instrumented fusion surgery is performed. The wide choice of implants and large variability between patients make it difficult for surgeons to choose optimal treatment strategies. This paper describes the patient specific finite element modelling techniques employed and the results of preliminary analyses predicting the surgical outcomes for a series of AIS patients. This report highlights the importance of not only patient-specific anatomy and material parameters, but also patient-specific data for the clinical and physiological loading conditions experienced by the patient who has corrective scoliosis surgery.

Cloud computing in the upstream oil & gas industry : a proposed way forward

Despite the compelling case for moving towards cloud computing, the upstream oil & gas industry faces several technical challenges—most notably, a pronounced emphasis on data security, a reliance on extremely large data sets, and significant legacy investments in information technology infrastructure—that make a full migration to the public cloud difficult at present. Private and hybrid cloud solutions have consequently emerged within the industry to yield as much benefit from cloud-based technologies as possible while working within these constraints. This paper argues, however, that the move to private and hybrid clouds will very likely prove only to be a temporary stepping stone in the industry's technological evolution. By presenting evidence from other market sectors that have faced similar challenges in their journey to the cloud, we propose that enabling technologies and conditions will probably fall into place in a way that makes the public cloud a far more attractive option for the upstream oil & gas industry in the years ahead. The paper concludes with a discussion about the implications of this projected shift towards the public cloud, and calls for more of the industry's services to be offered through cloud-based “apps.”

Towards brain-based sensor fusion for navigating robots

Current state of the art robot mapping and navigation systems produce impressive performance under a narrow range of robot platform, sensor and environmental conditions, in contrast to animals such as rats that produce “good enough” maps that enable them to function under an incredible range of situations. In this paper we present a rat-inspired featureless sensor-fusion system that assesses the usefulness of multiple sensor modalities based on their utility and coherence for place recognition during a navigation task, without knowledge as to the type of sensor. We demonstrate the system on a Pioneer robot in indoor and outdoor environments with abrupt lighting changes. Through dynamic weighting of the sensors, the system is able to perform correct place recognition and mapping where the static sensor weighting approach fails.