Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature

Introduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non-small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and β-catenin. Cisplatin-DNA adduct formation, DNA damage (γH2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133+/CD44+cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and β-catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased γH2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer. © 2013 Barr et al.

Extreme architecture : can architects future proof us against fire and flood.

In the face of Australia’s disaster-prone environment, architects Ian Weir and James Davidson are reconceptualising how our residential buildings might become more resilient to fire, flood and cyclone. With their first-hand experience of natural disasters, James, director of Emergency Architects Australia (EAA), and Ian, one of Australia’s few ‘bushfire architects’, discuss the ways we can design with disaster in mind. Dr Ian Weir is one of Australia’s few ‘bushfire architects’. Exploring a holistic ‘ground up’ approach to bushfire where landscape, building design and habitation patterns are orchestrated to respond to site-specific fire characteristics. Ian’s research is developed through design studio teaching at QUT and through built works in Western Australia’s fire prone forests and heathlands.

Design and modeling of collaboration architecture for security

Threats against computer networks evolve very fast and require more and more complex measures. We argue that teams respectively groups with a common purpose for intrusion detection and prevention improve the measures against rapid propagating attacks similar to the concept of teams solving complex tasks known from field of work sociology. Collaboration in this sense is not easy task especially for heterarchical environments. We propose CIMD (collaborative intrusion and malware detection) as a security overlay framework to enable cooperative intrusion detection approaches. Objectives and associated interests are used to create detection groups for exchange of security-related data. In this work, we contribute a tree-oriented data model for device representation in the scope of security. We introduce an algorithm for the formation of detection groups, show realization strategies for the system and conduct vulnerability analysis. We evaluate the benefit of CIMD by simulation and probabilistic analysis.

Simulation architecture for cooperative ITS applications and augmented perception

Cooperative Systems provide, through the multiplication of information sources over the road, a lot of potential to improve the safety of road users, especially drivers. However, developing cooperative ITS applications requires additional resources compared to non-cooperative applications which are both time consuming and expensive. In this paper, we present a simulation architecture aimed at prototyping cooperative ITS applications in an accurate and detailed, close-to-reality environment; the architecture is designed to be modular and generalist. It can be used to simulate any type of CS applications as well as augmented perception. Then, we discuss the results of two applications deployed with our architecture, using a common freeway emergency braking scenario. The first application is Emergency Electronic Brake Light (EEBL); we discuss improvements in safety in terms of the number of crashes and the severity of crashes. The second application compares the performance of a cooperative risk assessment using an augmented map against a non-cooperative approach based on local-perception only. Our results show a systematic improvement of forward warning time for most vehicles in the string when using the augmented-map-based risk assessment.

Stockholm Syndrome : architecture, politics and the human body

The exchange between the body and architecture walks a fine line between violence and pleasure. It is through the body that the subject engages with the architectural act, not via thought or reason, but through action. The materiality of architecture is the often the catalyst for some intense association; the wall that defines gender or class, the double bolted door that incarcerates, the enclosed privacy of the bedroom to the love affair. Architecture is the physical manifestation of Lefebvre’s inscribed space. It enacts the social and political systems through bodily occupation. Architecture, when tested by the occupation of bodies, anchors ideology in both space and time. The architect’s script can be powerful when rehearsed honestly to the building’s intentions and just as beautiful when rebuked by the act of protest or unfaithful occupation. This research examines this fine line of violence and pleasure in architecture through performance, in the work of Bryony Lavin’s play Stockholm and Revolving Door by Allora & Calzadilla as part of the recent Kaldor Public Art Projects exhibition 13 Rooms in Sydney. The research is underpinned by the work of Architect and theorist, Bernard Tschumi in his two essays, Violence of Architecture and The Pleasure of Architecture. Studying architecture through the lens of performance shifts the focus of examination from pure thought to the body; because architecture is occupied through the body and not the mind.

Designing the information architecture of governmental one-stop portals : on the application and analysis of card sorting

The latest paradigm shift in government, termed Transformational Government, puts the citizen in the centre of attention. Including citizens in the design of online one-stop portals can help governmental organisations to become more customer focussed. This study describes the initial efforts of an Australian state government to develop an information architecture to structure the content of their future one-stop portal. Hereby, card sorting exercises have been conducted and analysed, utilising contemporary approaches found in academic and non-scientific literature. This paper describes the findings of the card sorting exercises in this particular case and discusses the suitability of the applied approaches in general. These are distinguished into non-statistical, statistical, and hybrid approaches. Thus, on the one hand, this paper contributes to academia by describing the application of different card sorting approaches and discussing their strengths and weaknesses. On the other hand, this paper contributes to practice by explaining the approach that has been taken by the authors’ research partner in order to develop a customer-focussed governmental one-stop portal. Thus, they provide decision support for practitioners with regard to different analysis methods that can be used to complement recent approaches in Transformational Government.

The architecture of children’s use of language and tools when problem solving collaboratively with robotics

This paper demonstrates, following Vygotsky, that language and tool use has a critical role in the collaborative problem-solving behaviour of school-age children. It reports original ethnographic classroom research examining the convergence of speech and practical activity in children’s collaborative problem solving with robotics programming tasks. The researchers analysed children’s interactions during a series of problem solving experiments in which Lego Mindstorms toolsets were used by teachers to create robotics design challenges among 24 students in a Year 4 Australian classroom (students aged 8.5–9.5 years). The design challenges were incrementally difficult, beginning with basic programming of straight line movement, and progressing to more complex challenges involving programming of the robots to raise Lego figures from conduit pipes using robots as pulleys with string and recycled materials. Data collection involved micro-genetic analysis of students’ speech interactions with tools, peers, and other experts, teacher interviews, and student focus group data. Coding the repeated patterns in the transcripts, the authors outline the structure of the children’s social speech in joint problem solving, demonstrating the patterns of speech and interaction that play an important role in the socialisation of the school-age child’s practical intellect.

An urban informatics approach to smart city learning in architecture and urban design education

This study aims to redefine spaces of learning to places of learning through the direct engagement of local communities as a way to examine and learn from real world issues in the city. This paper exemplifies Smart City Learning, where the key goal is to promote the generation and exchange of urban design ideas for the future development of South Bank, in Brisbane, Australia, informing the creation of new design policies responding to the needs of local citizens. Specific to this project was the implementation of urban informatics techniques and approaches to promote innovative engagement strategies. Architecture and Urban Design students were encouraged to review and appropriate real-time, ubiquitous technology, social media, and mobile devices that were used by urban residents to augment and mediate the physical and digital layers of urban infrastructures. Our study’s experience found that urban informatics provide an innovative opportunity to enrich students’ place of learning within the city.

Newstead House : the social history, culture and architecture of a bygone era

Historic house museums form a significant component of the built heritage and social history of a country. They vary from the elaborate mansions of the wealthy to modest dwellings of the working class. Regardless of the original owner's status in society these house museums are vital to an understanding of architecture, culture and society from a bygone era. The Newstead House, the oldest surviving residence, in Brisbane, is the first house to be designated a 'Historic House Museum' in Queensland. It is a representative example of a house that demonstrates the British colonial heritage of 19th century Australia. Originally a modest cottage, on 34 acres of land, the Newstead house was built by a Scottish migrant. The ownership of the house and land changed many times, during the period from 1847 to 1939. During this period a series of prominent residents of Brisbane either owned or rented this residence. They included, an officer of the Royal Navy, politicians, magistrates, merchant ship owners, and a Consul General of the United States of America. As a result, the house went through a series of renovations and extensions to accommodate the needs of its owners and their position in society. This paper aims to investigate the significance of historic museum houses in educating the community on aspects of social history, culture and architecture of 19th century Australia. It will focus on the heritage listed Newstead House as a case study to demonstrate the significance of the house as an artefact and an educational tool.

Prediction of muscular architecture of the rectus femoris and vastus lateralis from EMG during isometric contractions in soccer players

Objectives The purpose of the study was to establish regression equations that could be used to predict muscle thickness and pennation angle at different intensities from electromyography (EMG) based measures of muscle activation during isometric contractions. Design Cross-sectional study. Methods Simultaneous ultrasonography and EMG were used to measure pennation angle, muscle thickness and muscle activity of the rectus femoris and vastus lateralis muscles, respectively, during graded isometric knee extension contractions performed on a Cybex dynamometer. Data form fifteen male soccer players were collected in increments of approximately 25% intensity of the maximum voluntary contraction (MVC) ranging from rest to MVC. Results There was a significant correlation (P < 0.05) between ultrasound predictors and EMG measures for the muscle thickness of rectus femoris with an R2 value of 0.68. There was no significant correlation (P > 0.05) between ultrasound pennation angle for the vastus lateralis predictors for EMG muscle activity with an R2 value of 0.40. Conclusions The regression equations can be used to characterise muscle thickness more accurately and to determine how it changes with contraction intensity, this provides improved estimates of muscle force when using musculoskeletal models.

Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures

Tissue engineering focuses on the repair and regeneration of tissues through the use of biodegradable scaffold systems that structurally support regions of injury whilst recruiting and/or stimulating cell populations to rebuild the target tissue. Within bone tissue engineering, the effects of scaffold architecture on cellular response have not been conclusively characterized in a controlled-density environment. We present a theoretical and practical assessment of the effects of polycaprolactone (PCL) scaffold architectural modifications on mechanical and flow characteristics as well as MC3T3-E1 preosteoblast cellular response in an in vitro static plate and custom-designed perfusion bioreactor model. Four scaffold architectures were contrasted, which varied in inter-layer lay-down angle and offset between layers, whilst maintaining a structural porosity of 60 ± 5%. We established that as layer angle was decreased (90° vs. 60°) and offset was introduced (0 vs. 0.5 between layers), structural stiffness, yield stress, strength, pore size and permeability decreased, whilst computational fluid dynamics-modeled wall shear stress was increased. Most significant effects were noted with layer offset. Seeding efficiencies in static culture were also dramatically increased due to offset (~45% to ~86%), with static culture exhibiting a much higher seeding efficiency than perfusion culture. Scaffold architecture had minimal effect on cell response in static culture. However, architecture influenced osteogenic differentiation in perfusion culture, likely by modifying the microfluidic environment.

The form of form : the fold and architecture

This paper will examine the idea of the fold arid its assimilation into architecture through philosophy and mathematics. In all its iterations, the fold appears as two constitutive items: the fold as self-similarity, which implies recursion; the fold within the fold, and in turn, the fold as continuous discontinuity. The persistence of this conception of die fold will be demonstrated through a discussion of Leibniz's Monadology, Deleuze's Le Pli, and some mathematical ideas from catastrophe and chaos theory. This raises the issue of continuity between disciplines and thus the philosophical status this confers on the fold.