The role of the arachidonic acid pathway in NSCLC development and progression : novel approaches for therapeutic intervention

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways is responsible for the formation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Altered eicosanoid expression levels are commonly observed during tumour development and progression of a range of malignancies, including non-small cell lung cancer (NSCLC). Arachidonic acid-derived eicosanoids affect a range of biological phenomena to modulate tumour processes such as cell growth, survival, angiogenesis, cell adhesion, invasion and migration and metastatic potential. Numerous studies have demonstrated that eicosanoids modulate NSCLC development and progression, while targeting these pathways has generally been shown to inhibit tumour growth/progression. Modulation of these arachidonic acid-derived pathways for the prevention and/or treatment of NSCLC has been the subject of significant interest over the past number of years, with a number of clinical trials examining the potential of COX and LOX inhibitors in combination with traditional and novel molecular approaches. However, results from these trials have been largely disappointing. Furthermore, enthusiasm for the use of selective COX-2 inhibitors for cancer prevention/treatment waned, due to their association with adverse cardiovascular events in chemoprevention trials. While COX and LOX targeting may both retain promise for NSCLC prevention and/or treatment, there is an urgent need to understand the downstream signalling mechanisms through which these and other arachidonic acid-derived signalling pathways mediate their effects on tumourigenesis. This will allow for development of safer and potentially more effective strategies for NSCLC prevention and/or treatment. Chemoprevention studies with PGI2 analogues have demonstrated considerable promise, while binding to/signalling through PGE2 receptors have also been the subject of interest for NSCLC treatment. In this chapter, the role of the eicosanoid signalling pathways in non-small cell lung cancer will be discussed. In particular, the effect of the eicosanoids on tumour cell proliferation, their roles in induction of cell death, effects on angiogenesis, migration, invasion and their regulation of the immune response will be assessed, with signal transduction pathways involved in these processes also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of NSCLC will be outlined. Elucidating the molecular mechanisms underlying the effects of specific or general arachidonic acid pathway modulators may lead to the design of biologically and pharmacologically targeted therapeutic strategies for NSCLC prevention/treatment, which may be used alone or in combination with conventional therapies.

Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM)

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often diagnosed at an advanced stage and is characterized by a long latency period (20-40 years between initial exposure and diagnosis) and prior exposure to asbestos. Currently accurate diagnosis of MPM is difficult due to the lack of sensitive biomarkers and despite minor improvements in treatment, median survival rates do not exceed 12 months. Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) play an important functional role in cancer biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200 nucleotides in length with a role in regulating transcription. Here we used NCode long noncoding microarrays to identify differentially expressed lncRNAs potentially involved in MPM pathogenesis. High priority candidate lncRNAs were selected on the basis of statistical (P<0.05) and biological significance (>3-fold difference). Expression levels of 9 candidate lncRNAs were technically validated using RT-qPCR, and biologically validated in three independent test sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of these lncRNAs in independent datasets. ROC curve analysis showed that two candidates were able to separate benign pleura and MPM with high sensitivity and specificity, and were associated with nodal metastases and survival following induction chemotherapy. These results suggest that lncRNAs have potential to serve as biomarkers in MPM.

Knowledge unlatched announces the launch of its pilot collection [Blog]

Frances Pinter and I have been visiting fellows at the Big Innovation Centre for more than a year now. Tucked away in a corner, inspired by BIC’s open innovation vision, we have been attempting to solve a problem that continues to perplex many in the era of digital affordance: creating sustainable markets for high quality new content that include free access for end users.

Different in vitro activation methods for latent transforming growth factors (TGF)–β : considerable exogenous factors to promote higher mesenchymal-origin cell proliferation in a bioprocessing platform

Regenerative medicine includes two efficient techniques, namely tissue-engineering and cell-based therapy in order to repair tissue damage efficiently. Most importantly, huge numbers of autologous cells are required to deal these practices. Nevertheless, primary cells, from autologous tissue, grow very slowly while culturing in vitro; moreover, they lose their natural characteristics over prolonged culturing period. Transforming growth factors-beta (TGF-β) is a ubiquitous protein found biologically in its latent form, which prevents it from eliciting a response until conversion to its active form. In active form, TGF-β acts as a proliferative agent in many cell lines of mesenchymal origin in vitro. This article reviews on some of the important activation methods-physiochemical, enzyme-mediated, non-specific protein interaction mediated, and drug-induced- of TGF-β, which may be established as exogenous factors to be used in culturing medium to obtain extensive proliferation of primary cells.

Continuity, Rupture, or just more of the 'Volatile and Contradictory': Glimpses of New South Wales' Penal Practice behind and through the Discursive

Throughout much of the western world more and more people are being sent to prison, one of a number of changes inspired by a 'new punitiveness' in penal and political affairs. This book seeks to understand these developments, bringing together leading authorities in the field to provide a wide-ranging analysis of new penal trends, compare the development of differing patterns of punishment across different types of societies, and to provide a range of theoretical analyses and commentaries to help understand their significance. As well as increases in imprisonment this book is also concerned to address a number of other aspects of 'the new punitiveness': firstly, the return of a number of forms of punishment previously thought extinct or inappropriate, such as the return of shaming punishments and chain gangs (in parts of the USA); and secondly, the increasing public involvement in penal affairs and penal development, for example in relation to length of sentences and the California Three Strikes Law, and a growing accreditation of the rights of victims. The book will be essential reading for students seeking to understand trends and theories of punishment on law, criminology, penology and other courses.

A bi-lineage conducive scaffold for osteochondral defect regeneration

Because cartilage and bone tissues have different lineage-specific biological properties, it is challenging to fabricate a single type of scaffold that can biologically fulfill the requirements for regeneration of these two lineages simultaneously within osteochondral defects. To overcome this challenge, a lithium-containing mesoporous bioglass (Li-MBG) scaffold is developed. The efficacy and mechanism of Li-MBG for regeneration of osteochondral defects are systematically investigated. Histological and micro-CT results show that Li-MBG scaffolds significantly enhance the regeneration of subchondral bone and hyaline cartilage-like tissues as compared to pure MBG scaffolds, upon implantation in rabbit osteochondral defects for 8 and 16 weeks. Further investigation demonstrates that the released Li+ ions from the Li-MBG scaffolds may play a key role in stimulating the regeneration of osteochondral defects. The corresponding mechanistic pathways involve Li+ ions enhancing the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) through activation of the Wnt signalling pathway, as well as Li+ ions protecting chondrocytes and cartilage tissues from the inflammatory osteoarthritis (OA) environment through activation of autophagy. These findings suggest that the incorporation of Li+ ions into bioactive MBG scaffolds is a viable strategy for fabricating bi-lineage conducive scaffolds that enhance regeneration of osteochondral defects.

Autonomous multisensor calibration and closed-loop fusion for SLAM

The vast majority of current robot mapping and navigation systems require specific well-characterized sensors that may require human-supervised calibration and are applicable only in one type of environment. Furthermore, if a sensor degrades in performance, either through damage to itself or changes in environmental conditions, the effect on the mapping system is usually catastrophic. In contrast, the natural world presents robust, reasonably well-characterized solutions to these problems. Using simple movement behaviors and neural learning mechanisms, rats calibrate their sensors for mapping and navigation in an incredibly diverse range of environments and then go on to adapt to sensor damage and changes in the environment over the course of their lifetimes. In this paper, we introduce similar movement-based autonomous calibration techniques that calibrate place recognition and self-motion processes as well as methods for online multisensor weighting and fusion. We present calibration and mapping results from multiple robot platforms and multisensory configurations in an office building, university campus, and forest. With moderate assumptions and almost no prior knowledge of the robot, sensor suite, or environment, the methods enable the bio-inspired RatSLAM system to generate topologically correct maps in the majority of experiments.

A modified particle swarm optimization for correlated phenomena

The wide applicability of correlation analysis inspired the development of this paper. In this paper, a new correlated modified particle swarm optimization (COM-PSO) is developed. The Correlation Adjustment algorithm is proposed to recover the correlation between the considered variables of all particles at each of iterations. It is shown that the best solution, the mean and standard deviation of the solutions over the multiple runs as well as the convergence speed were improved when the correlation between the variables was increased. However, for some rotated benchmark function, the contrary results are obtained. Moreover, the best solution, the mean and standard deviation of the solutions are improved when the number of correlated variables of the benchmark functions is increased. The results of simulations and convergence performance are compared with the original PSO. The improvement of results, the convergence speed, and the ability to simulate the correlated phenomena by the proposed COM-PSO are discussed by the experimental results.

On the use of complex numbers in quantum models for information retrieval

Quantum-inspired models have recently attracted increasing attention in Information Retrieval. An intriguing characteristic of the mathematical framework of quantum theory is the presence of complex numbers. However, it is unclear what such numbers could or would actually represent or mean in Information Retrieval. The goal of this paper is to discuss the role of complex numbers within the context of Information Retrieval. First, we introduce how complex numbers are used in quantum probability theory. Then, we examine van Rijsbergen’s proposal of evoking complex valued representations of informations objects. We empirically show that such a representation is unlikely to be effective in practice (confuting its usefulness in Information Retrieval). We then explore alternative proposals which may be more successful at realising the power of complex numbers.

Lattice-based threshold changeability for standard shamir sectret-sharing schemes

We consider the problem of increasing the threshold parameter of a secret-sharing scheme after the setup (share distribution) phase, without further communication between the dealer and the shareholders. Previous solutions to this problem require one to start off with a nonstandard scheme designed specifically for this purpose, or to have communication between shareholders. In contrast, we show how to increase the threshold parameter of the standard Shamir secret-sharing scheme without communication between the shareholders. Our technique can thus be applied to existing Shamir schemes even if they were set up without consideration to future threshold increases. Our method is a new positive cryptographic application for lattice reduction algorithms, inspired by recent work on lattice-based list decoding of Reed-Solomon codes with noise bounded in the Lee norm. We use fundamental results from the theory of lattices (geometry of numbers) to prove quantitative statements about the information-theoretic security of our construction. These lattice-based security proof techniques may be of independent interest.

Body and forgetting

Body and Forgetting is a powerful dance performance that brings together the work of choreographer Liz Roche and film maker Alan Gilsenan, with a live score by Denis Roche. Inspired by the writings of Milan Kundera, Liz Roche Company's remarkable dancers find their way through delicately woven circumstances of disappearance, loss, relationship and hope. Their attempts to hold fast to memories and objects of meaning is at the heart of this work. The live performers move in dialogue with filmed versions of their dancing selves. They re-write their histories, make better endings to their stories, say what they regret not having said. These filmed reflections or versions of themselves, by offering a mirror, ultimately bring the performers back to themselves, richer from the experience.

Using performance-based evaluation to close the loop between biological and robotic navigation

In this paper we describe the benefits of a performance-based approach to modeling biological systems for use in robotics. Specifically, we describe the RatSLAM system, a computational model of the navigation processes thought to drive navigation in a part of the rodent brain called the hippocampus. Unlike typical computational modeling approaches, which focus on biological fidelity, RatSLAM’s development cycle has been driven primarily by performance evaluation on robots navigating in a wide variety of challenging, real world environments. We briefly describe three seminal results, two in robotics and one in biology. In addition, we present current research on brain-inspired learning algorithms with the aim of enabling a robot to autonomously learn how best to use its sensor suite to navigate, without requiring any specific knowledge of the robot, sensor types or environment characteristics. Our aim is to drive discussion on the merits of practical, performance-focused implementations of biological models in robotics.

Marine aerosol hygroscopicity and volatility, measured on the Chatham Rise (New Zealand)

The Surface Ocean Aerosol Production (SOAP) study was undertaken in February/March 2012 in the biologically active waters of the Chatham Rise, NZ. Aerosol hygroscopicity and volatility were examined with a volatility hygroscopicity tandem differential mobility analyser. These observations confirm results from other hygroscopicity-based studies that the dominant fraction of the observed remote marine particles were non-sea salt sulfates. Further observations are required to clarify the influences of seawater composition, meteorology and analysis techniques seasonally across different ocean basins.

Living City 2013 Workshop

Living City 2013 Workshop, as part of a school term’s design-based curriculum connected to the KGSC/QUT Design Excellence Program and run from 11 February – 1 May, 2013, was essentially a three-day place-based urban design immersion workshop program for 25 Year 11 Visual Art and Design Students and 2 Teachers from Kelvin Grove State College (KGSC) held at both Queensland University of Technology (QUT) Gardens Point Campus and The Edge, State Library of Queensland. Mentored by 4 design professionals, 2 tertiary design academics, 2 public artists, and 12 QUT tertiary design students, the workshop explored youth-inspired public space design solutions for the active Brisbane City Council redevelopment site of Queens Wharf Road precinct. As well as the face-to-face workshops, for Living City 2013, an interactive web environment was introduced to enable students to connect with each other and program mentors throughout the course of the program. The workshop, framed within notions of ecological, economic, social and cultural sustainability, aimed to raise awareness of the layered complexity and perspectives involved in the design of shared city spaces and to encourage young people to voice their own concerns as future citizens about the shape and direction of their city. The program commenced with an introductory student briefing by stakeholders and mentors at KGSC on 11 February, an introduction to site appraisal and site visit held at QUT and Queens Wharf Road on 20 February, and a follow up site analysis session on 6 March. Day 1 Workshop on April 17 at the Edge, State Library of Queensland, as part of the Design Minds partnership (http://designminds.org.au/kelvin-grove-state-college-excellence-in-art-design/), focused on mentoring team development of a concept design for a range of selected sites. Two workshops on April 22 and 23 at QUT, to develop these designs and presentation schemes, followed this. The workshop program culminated in a visual presentation of concept design ideas and discussion with a public audience in the Ideas Gallery on The Deck, King George Square during the Brisbane City Council City Centre Master Plan Ideas Fiesta on 1 May, 2013, as referenced in the Ideas Fiesta Wrap-up Report (http://www.brisbane.qld.gov.au/planning-building/planning-guidelines-tools/city-centre-master-plan/city-centre-master-plan-ideas-fiesta). Students were introduced to design methodology, team thinking strategies, the scope of design practices and professions, presentation skills and post-secondary pathways, while participating teachers acquired content and design learning strategies transferable in many other contexts. The program was fully documented on the Living City website (http://www.livingcity.net.au/LC2013x/index.html) and has been recognised by the Brisbane City Council Youth Strategy 2014-2019 as a best practice model for making Brisbane a well-designed, subtropical city.

Preparation of mesoporous bioglass coated zirconia scaffold for bone tissue engineering

Porous yttria-stabilized zirconia (YSZ) has been regarded as a potential candidate for bone substitute due to its high mechanical strength. However, porous YSZ is biologically inert to bone tissue. It is therefore necessary to introduce bioactive coatings onto the walls of the porous structures to enhance its bioactivity. In this study, porous YSZ scaffolds were prepared using a replication technique and then coated with mesoporous bioglass due to its excellent bioactivity. The microstructures were examined using scanning electron microscopy and the mechanical strength was evaluated via compression test. The biocompatibility and bioactivity were also evaluated using bone marrow stromal cell (BMSC) proliferation test and simulated body fluid test.