Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN

The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P<0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent set of 18 melanoma lines with known PTEN status. Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants. The inverse correlation between OPN and PTEN expression was validated (P<0.02) by immunohistochemistry using melanoma tissue microarrays. Finally, treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in expression of OPN. These data indicate that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development.

Emergent task-specific object semantics through distributed experience networks

Autonomous development of sensorimotor coordination enables a robot to adapt and change its action choices to interact with the world throughout its lifetime. The Experience Network is a structure that rapidly learns coordination between visual and haptic inputs and motor action. This paper presents methods which handle the high dimensionality of the network state-space which occurs due to the simultaneous detection of multiple sensory features. The methods provide no significant increase in the complexity of the underlying representations and also allow emergent, task-specific, semantic information to inform action selection. Experimental results show rapid learning in a real robot, beginning with no sensorimotor mappings, to a mobile robot capable of wall avoidance and target acquisition.

Different inflections

Australia has often been defined by its landscape – actual, romanticized, imagined – iconic images and experiences taken up by artists in a myriad of ways. This paper examines inter/intra cultural practices of three Australian dance companies and their directors, and how they inflect images of Australia in different ways. Each artist brings perspectives from their particular hybridized cultural and ethnic backgrounds as well as their formative dance experiences. In their practices, notions of landscape embrace physical, metaphorical and spiritual dimensions. Kai Tai Chan, who founded the One Extra Company in 1976, pioneered accessible and confronting intercultural dance theatre in Australia from the 1970s to the 1990s, challenging our notions of what it is to be Australian. A Chinese Malay who came to Australia to study architecture, he stayed to create a significant body of work in which different cultural frameworks became lenses through which to explore stories of ordinary lives and experiences, revealing complexities of the human condition and larger social-political issues. Spiritual connections feature strongly in the practice of another Chinese Malay Australian, Tony Yap. Here the landscape is an inner one influenced by a form of Malaysian trance dance known as the sen-siao (“spirit cloud”) tradition. Yap has forged a unique space in the Australian dance and theatre scene, exploring a movement language informed by psycho-physical research, Asian shamanistic trance dance, Butoh, voice and visual design. Whilst primarily a solo performer, his practice includes collaborations with Asian diasporic as well as Anglo Australian cross-cultural visual and sound artists. His work is situated in a metaphysical rather than socio political context. In contrast, the newest company to emerge on the intercultural Australian stage is Polytoxic, reflecting a Pacific rather than Asian inflection. Key members, Fa’alafi and Efeso Fa’anana (both of Samoan descent) and Leah Shelton (of Anglo-Saxon descent), aim to critique the exoticism and cultural kitsch that often accompanies representations of the Pacific islands, with a pastiche of street dance, cabaret and contemporary techniques, blended with traditional Polynesian vocabulary. A parallel aim is to provide audiences with insights into the traditions and history of Samoa from the perspective of the artists as contemporary Australians. This examination, spanning three decades of inter/intra cultural practices, reveals stylistic, generational and philosophical differences with a commonality of variously inflected notions of landscape, spirituality and identity.

Restrung new chamber festival : an exploration of contemporary string practice

The Restrung New Chamber Festival was a practice-led research project which explored the intricacies of musical relationships. Specifically, it investigated the nature of contemporary string practice, with "New music" at its core. For the purposes of this project, "New music" will be defined in terms of representing a "global sonorous space" (Nancy 2007:12), which Hulse describes as "a spectacular comingling of styles and an unprecedented explosion of creative possibilities" (Hulse n.d.:2). Approaches to staging such an event are contextualised through a comparative analysis with relevant Australian and European festivals. The Restrung model derived inspiration from both art music and popular music festival models, in several aspects. One strategy was to engage audiences through combinations of musical, visual and spatial features. Another strategy was to encourage interaction by audiences with installations, workshops and forums. Restrung represents a new and distinctive model which presented art music within an immersive environment. This exegesis presents an evaluation framework which investigates the relationship between curatorial input and the experiential qualities of the festival. The context of an overview of trends in arts festival curation informs the discussion, as well as approaches to identifying new and receptive audiences. It is expected that the evaluation framework will provide a useful and practical guide for curators working in contemporary string practice, hybrid arts, experimental and cross-art form festival design.

Non-invasive method for detecting changes in soil moisture using wireless sensor networks

There are several popular soil moisture measurement methods today such as time domain reflectometry, electromagnetic (EM) wave, electrical and acoustic methods. Significant studies have been dedicated in developing method of measurements using those concepts, especially to achieve the characteristics of noninvasiveness. EM wave method provides an advantage because it is non-invasive to the soil and does not need to utilise probes to penetrate or bury in the soil. But some EM methods are also too complex, expensive, and not portable for the application of Wireless Sensor Networks; for example satellites or UAV (Unmanned Aerial Vehicle) based sensors. This research proposes a method in detecting changes in soil moisture using soil-reflected electromagnetic (SREM) wave from Wireless Sensor Networks (WSNs). Studies have shown that different levels of soil moisture will affects soil’s dielectric properties, such as relative permittivity and conductivity, and in turns change its reflection coefficients. The SREM wave method uses a transmitter adjacent to a WSNs node with purpose exclusively to transmit wireless signals that will be reflected by the soil. The strength from the reflected signal that is determined by the soil’s reflection coefficients is used to differentiate the level of soil moisture. The novel nature of this method comes from using WSNs communication signals to perform soil moisture estimation without the need of external sensors or invasive equipment. This innovative method is non-invasive, low cost and simple to set up. There are three locations at Brisbane, Australia chosen as the experiment’s location. The soil type in these locations contains 10–20% clay according to the Australian Soil Resource Information System. Six approximate levels of soil moisture (8, 10, 13, 15, 18 and 20%) are measured at each location; with each measurement consisting of 200 data. In total 3600 measurements are completed in this research, which is sufficient to achieve the research objective, assessing and proving the concept of SREM wave method. These results are compared with reference data from similar soil type to prove the concept. A fourth degree polynomial analysis is used to generate an equation to estimate soil moisture from received signal strength as recorded by using the SREM wave method.

Near infrared spectroscopy for non-destructive evaluation of articular cartilage

There is a need for an accurate real-time quantitative system that would enhance decision-making in the treatment of osteoarthritis. To achieve this objective, significant research is required that will enable articular cartilage properties to be measured and categorized for health and functionality without the need for laboratory tests involving biopsies for pathological evaluation. Such a system would provide the capability of access to the internal condition of the cartilage matrix and thus extend the vision-based arthroscopy that is currently used beyond the subjective evaluation of surgeons. The system required must be able to non-destructively probe the entire thickness of the cartilage and its immediate subchondral bone layer. In this thesis, near infrared spectroscopy is investigated for the purpose mentioned above. The aim is to relate it to the structure and load bearing properties of the cartilage matrix to the near infrared absorption spectrum and establish functional relationships that will provide objective, quantitative and repeatable categorization of cartilage condition outside the area of visible degradation in a joint. Based on results from traditional mechanical testing, their innovative interpretation and relationship with spectroscopic data, new parameters were developed. These were then evaluated for their consistency in discriminating between healthy viable and degraded cartilage. The mechanical and physico-chemical properties were related to specific regions of the near infrared absorption spectrum that were identified as part of the research conducted for this thesis. The relationships between the tissue's near infrared spectral response and the new parameters were modeled using multivariate statistical techniques based on partial least squares regression (PLSR). With significantly high levels of statistical correlation, the modeled relationships were demonstrated to possess considerable potential in predicting the properties of unknown tissue samples in a quick and non-destructive manner. In order to adapt near infrared spectroscopy for clinical applications, a balance between probe diameter and the number of active transmit-receive optic fibres must be optimized. This was achieved in the course of this research, resulting in an optimal probe configuration that could be adapted for joint tissue evaluation. Furthermore, as a proof-of-concept, a protocol for obtaining the new parameters from the near infrared absorption spectra of cartilage was developed and implemented in a graphical user interface (GUI)-based software, and used to assess cartilage-on-bone samples in vitro. This conceptual implementation has been demonstrated, in part by the individual parametric relationship with the near infrared absorption spectrum, the capacity of the proposed system to facilitate real-time, non-destructive evaluation of cartilage matrix integrity. In summary, the potential of the optical near infrared spectroscopy for evaluating articular cartilage and bone laminate has been demonstrated in this thesis. The approach could have a spin-off for other soft tissues and organs of the body. It builds on the earlier work of the group at QUT, enhancing the near infrared component of the ongoing research on developing a tool for cartilage evaluation that goes beyond visual and subjective methods.

Hand-held monocular SLAM in thermal-infrared

Thermal-infrared imagery is relatively robust to many of the failure conditions of visual and laser-based SLAM systems, such as fog, dust and smoke. The ability to use thermal-infrared video for localization is therefore highly appealing for many applications. However, operating in thermal-infrared is beyond the capacity of existing SLAM implementations. This paper presents the first known monocular SLAM system designed and tested for hand-held use in the thermal-infrared modality. The implementation includes a flexible feature detection layer able to achieve robust feature tracking in high-noise, low-texture thermal images. A novel approach for structure initialization is also presented. The system is robust to irregular motion and capable of handling the unique mechanical shutter interruptions common to thermal-infrared cameras. The evaluation demonstrates promising performance of the algorithm in several environments.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Affecting interference

This collaborative project by Daniel Mafe and Andrew Brown, one of a number in they have been involved in together, conjoins painting and digital sound into a single, large scale, immersive exhibition/installation. The work as a whole acts as an interstitial point between contrasting approaches to abstraction: the visual and aural, the digital and analogue are pushed into an alliance and each works to alter perceptions of the other. For example, the paintings no longer mutely sit on the wall to be stared into. The sound seemingly emanating from each work shifts the viewer’s typical visual perception and engages their aural sensibilities. This seems to make one more aware of the objects as objects – the surface of each piece is brought into scrutiny – and immerses the viewer more viscerally within the exhibition. Similarly, the sonic experience is focused and concentrated spatially by each painted piece even as the exhibition is dispersed throughout the space. The sounds and images are similar in each local but not identical, even though they may seem to be the same from casual interaction, closer attention will quickly show this is not the case. In preparing this exhibition each artist has had to shift their mode of making to accommodate the other’s contribution. This was mainly done by a process of emptying whereby each was called upon to do less to the works they were making and to iterate the works toward a shared conception, blurring notions of individual imagination while maintaining material authorship. Empting was necessary to enable sufficient porosity where each medium allowed the other entry to its previously gated domain. The paintings are simple and subtle to allow the odd sonic textures a chance to work on the viewer’s engagement with them. The sound remains both abstract, using noise-like textures, and at a low volume to allow the audience’s attention to wander back and forth between aspects of the works.

Robots move : bootstrapping the development of object representations using sensorimotor coordination

This paper is concerned with the unsupervised learning of object representations by fusing visual and motor information. The problem is posed for a mobile robot that develops its representations as it incrementally gathers data. The scenario is problematic as the robot only has limited information at each time step with which it must generate and update its representations. Object representations are refined as multiple instances of sensory data are presented; however, it is uncertain whether two data instances are synonymous with the same object. This process can easily diverge from stability. The premise of the presented work is that a robot's motor information instigates successful generation of visual representations. An understanding of self-motion enables a prediction to be made before performing an action, resulting in a stronger belief of data association. The system is implemented as a data-driven partially observable semi-Markov decision process. Object representations are formed as the process's hidden states and are coordinated with motor commands through state transitions. Experiments show the prediction process is essential in enabling the unsupervised learning method to converge to a solution - improving precision and recall over using sensory data alone.

Abstraction as noise : enhancing the poetic

Abstraction in its resistance to evident meaning has the capacity to interrupt or at least provide tools with which to question an overly compliant reception of the information to which we are subject. It does so by highlighting a latency or potentiality inherent in materiality that points to the possibility of a critical resistance to this ceaseless flow of sound/image/data. This resistance has been remarked on in differing ways by a number of commentators such as Lyotard, in his exploration of the avant-garde and the sublime for example. This joint paper will initially map the collaborative project by Daniel Mafe and Andrew Brown, Affecting Interference which conjoins painting with digital sound and animations into a single, large scale, immersive exhibition/installation. The work acts as an interstitial point between contrasting approaches to abstraction: the visual and aural, the digital and analogue. The paper will then explore the ramifications of this through the examination of abstraction as ‘noise’, that is as that raw inassimilable materiality, within which lays the creative possibility to forge and embrace the as-yet-unthought and almost-forgotten. It does so by establishing a space for a more poetic and slower paced critical engagement for the viewing and receiving information or data. This slowing of perception through the suspension of easy recognition runs counter to our current ‘high performance’ culture, and it’s requisite demand for speedy assimilation of content, representing instead the poetic encounter with a potentiality or latency inherent in the nameless particularity of that which is.

Characterization of inflammatory responses to eccentric exercise in humans

Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscle proteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.

Measuring mechanical properties of tendon in vivo

Introduction: Understanding the mechanical properties of tendon is an important step to guiding the process of improving athletic performance, predicting injury and treating tendinopathies. The speed of sound in a medium is governed by the bulk modulus and density for fluids and isotropic materials. However, for tendon,which is a structural composite of fluid and collagen, there is some anisotropy requiring an adjustment for Poisson’s ratio. In this paper, these relationships are explored and modelled using data collected, in vivo, on human Achilles tendon. Estimates for elastic modulus and hysteresis based on speed of sound data are then compared against published values from in vitro mechanical tests. Methods: Measurements using clinical ultrasound imaging, inverse dynamics and acoustic transmission techniques were used to determine dimensions, loading conditions and longitudinal speed of sound for the Achilles tendon during a series of isometric plantar flexion exercises against body weight. Upper and lower bounds for speed of sound versus tensile stress in the tendon were then modelled and estimates derived for elastic modulus and hysteresis. Results: Axial speed of sound varied between 1850 to 2090 m.s−1 with a non-linear, asymptotic dependency on the level of tensile stress in the tendon 5–35 MPa. Estimates derived for the elastic modulus ranged between 1–2 GPa. Hysteresis derived from models of the stress-strain relationship, ranged from 3–11%. These values agree closely with those previously reported from direct measurements obtained via in vitro mechanical tensile tests on major weight bearing tendons. Discussion: There is sufficiently good agreement between these indirect (speed of sound derived) and direct (mechanical tensile test derived) measures of tendon mechanical properties to validate the use of this non-invasive acoustic transmission technique. This non-invasive method is suitable for monitoring changes in tendon properties as predictors of athletic performance, injury or therapeutic progression.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.