Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways

Purpose Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. ©2011 AACR.

John Frazer

John Frazer, Professor, trained at the Architectural Association, taught first at Cambridge University and then the AA in the 1970s and again in the '90s. He was Head of School of Design Research History and Criticism at the University of Ulster in the 1980s, he also ran a systems and design consultancy with his wife Julia (including projects for Cedric Price and Walter Segal) and was founder and chairman of Autographics software. He is currently Swire Chair Professor and Head of School of Design in Hong Kong.----- This is a very personal perspective on a concept of universal and future significance. It is personal, both is the sense that it is an unashamedly biased view of both the significance of the project, and the nature of that significance and because the author was personally involved as one of the consultants on GENERATOR and subsequently involved Cedric Price in its educational application at the Architectural Association. GENERATOR is still very much alive and was still developing whilst this chapter was being written.

Sound radiation characteristics of a box-type structure

The finite element and boundary element methods are employed in this study to investigate the sound radiation characteristics of a box-type structure. It has been shown [T.R. Lin, J. Pan, Vibration characteristics of a box-type structure, Journal of Vibration and Acoustics, Transactions of ASME 131 (2009) 031004-1–031004-9] that modes of natural vibration of a box-type structure can be classified into six groups according to the symmetry properties of the three panel pairs forming the box. In this paper, we demonstrate that such properties also reveal information about sound radiation effectiveness of each group of modes. The changes of radiation efficiencies and directivity patterns with the wavenumber ratio (the ratio between the acoustic and the plate bending wavenumbers) are examined for typical modes from each group. Similar characteristics of modal radiation efficiencies between a box structure and a corresponding simply supported panel are observed. The change of sound radiation patterns as a function of the wavenumber ratio is also illustrated. It is found that the sound radiation directivity of each box mode can be correlated to that of elementary sound sources (monopole, dipole, etc.) at frequencies well below the critical frequency of the plates of the box. The sound radiation pattern on the box surface also closely related to the vibration amplitude distribution of the box structure at frequencies above the critical frequency. In the medium frequency range, the radiated sound field is dominated by the edge vibration pattern of the box. The radiation efficiency of all box modes reaches a peak at frequencies above the critical frequency, and gradually approaches unity at higher frequencies.

A study of vibration and vibration control of ship structures

This paper examines the vibration characteristics and vibration control of complex ship structures. It is shown that input mobilities of a ship structure at engine supports, due to out-of-plane force or bending moment excitations, are governed by the flexural stiffness of the engine supports. The frequency averaged input mobilities of the ship structure, due to such excitations, can be represented by those of the corresponding infinite beam. The torsional moment input mobility at the engine support can be estimated from the torsional response of the engine bed section under direct excitation. It is found that the inclusion of ship hull and deck plates in the ship structure model has little effect on the frequency-averaged response of the ship structure. This study also shows that vibration propagation in complex ship structures at low frequencies can be attenuated by imposing irregularities to the ring frame locations in ships. Vibration responses of ship structures due to machinery excitations at higher frequencies can be controlled by structural modifications of the local supporting structures such as engine beds in ships.

Cipher cities

Cipher Cities was a practice-led research project developed in 3 stages between 2005 and 2007 resulting in the creation of a unique online community, ‘Cipher Cities’, that provides simple authoring tools and processes for individuals and groups to create their own mobile events and event journals, build community profile and participate in other online community activities. Cipher Cities was created to revitalise peoples relationship to everyday places by giving them the opportunity and motivation to create and share complex digital stories in simple and engaging ways. To do so we developed new design processes and methods for both the research team and the end user to appropriate web and mobile technologies. To do so we collaborated with ethnographers, designers and ICT researchers and developers. In teams we ran a series of workshops in a wide variety of cities in Australia to refine an engagement process and to test a series of iteratively developed prototypes to refine the systems that supported community motivation and collaboration. The result of the research is 2 fold: 1. a sophisticated prototype for researchers and designers to further experiment with community engagement methodologies using existing and emerging communications technologies. 2. A ‘human dimensions matrix’. This matrix assists in the identification and modification of place based interventions in the social, technical, spatial, cultural, pedagogical conditions of any given community. This matrix has now become an essential part of a number of subsequent projects and assists design collaborators to successfully conceptualise, generate and evaluate interactive experiences. the research team employed practice-led action research methodologies that involved a collaborative effort across the fields of interaction design and social science, in particular ethnography, in order to: 1. seek, contest, refine a design methodology that would maximise the successful application of a dynamic system to create new kinds of interactions between people, places and artefacts’. 2. To design and deploy an application that intervenes in place-based and mobile technologies and offers people simple interfaces to create and share digital stories. Cipher Cities was awarded 3 separate CRC competitive grants (over $270,000 in total) to assist 3 stages of research covering the development of the Ethnographic Design Methodologies, the development of the tools, and the testing and refinement of both the engagement models and technologies. The resulting methodologies and tools are in the process of being commercialised by the Australasian CRC for Interaction Design.

Informe

Much landscape architectural form seems like hackneyed modernism, whether it be orthogonal or biomorphic, 'formal or informal' and doesn't seem to get to grips with the truly complex nature of the landscape, making any project seem potentially simplistic. This is largely because it has inherited languages from architecture that are based around objects, and that therefore can act to make designs self-referential rather than edgy instances in a dialogue much larger than the site itself, connected to systems that are unavoidable, even if one chooses to ignore them. These systems constitute a formal language even if landscape architecture looks to things like GIS to engage with them. Tropospheric Temperament was an Advanced Computing subject, for second-year landscape architecture students at UWA, taught by Julian Raxworthy and Rene Van Meeuwen, which ran in Semester 1, 2004. For this subject, the question was: how can we learn to wield such systems in design terms, even if they are developed through un-self-conscious natural and vernacular forces?

Art for architecture's sake?

The Architecture, Disciplinarity and the Arts symposium was organised by the Architecture. Theory, Criticism and History (ATCH) research group at the University of Queensland, run by John Macarthur and Antony Moulis, together with Andrew Leach who joined them last year and organised much of the symposium. The symposium ran for three days in a small room at the Institute of Modern Art (IMA) in Fortitude Valley, Brisbane (generously donated by director Robert Leonard), with about 40 people in attendance. Together with a long question time of an hour after every three speakers, the size of the room and the small number of people made it very different from most architecture or design conferences. The intellectual level of the symposium was high, without the speed dating aspect that one often sees at the Society of Architectural Historians, Australia and New Zealand (SAHANZ) meetings, where endless parallel sessions of short papers create an occasionally disorientating cacophony of words. The symposium was deliberately, unapologetically academic and the intimate nature of the forum made the discussion rich and collaborative, with an active audience. The title of the symposium, 'Architecture, Disciplinarity and the Arts', reflects the connection that already exists between the art history and the architectural history community in Brisbane, with both groups regularly attending each other's functions.

Reducing MRI gradient coil vibration with rib stiffeners

This work investigates the effect of rib stiffeners on the free and forced vibration of a gradient coil in a Magnetic Resonance Imaging (MRI) scanner. Several reinforcement schemes are studied in this paper. One scheme utilizes the existing holes in the gradient coil structure (typically reserved for magnetic shims) to produce the reinforcement. Non-ferrous, non-magnetic carbon fibre rib stiffeners are employed to fill these holes in several ways to strengthen a gradient coil. Another scheme replaces the inner half of the gradient coil material with a grid of interconnected axial and circumferential rib stiffeners. It is found that the structural stiffness of the gradient coil increases substantially when the coil is reinforced by carbon fibre rib stiffeners. The reinforcement affects the noise and vibration response of the gradient coil structure in the following ways. It increases the frequency range of forced response of the gradient coil at low frequencies due to the increased resonant frequency of the fundamental mode of the coil. Secondly, it reduces the forced response amplitude of the coil structure (which is governed by the structural stiffness of the coil). Thirdly, it reduces the number of natural modes in the low and medium frequency range and therefore lessens the chance of the coil structure being excited resonantly by magnetic resonance signal acquisition sequences. It is shown that gradient coils modelled by solid finite element models have higher stiffness along the coil’s circumference and lower stiffness in the axial direction than those using shell finite element models.

Action learning of online marketing via a global contest

Introduction: The Google Online Marketing Challenge is a global competition in which student teams run advertising campaigns for small and medium-sized businesses (SMEs) using AdWords, Google’s text-based advertisements. In 2008, its inaugural year, over 8,000 students and 300 instructors from 47 countries representing over 200 schools participated. The Challenge ran in undergraduate and graduate classes in disciplines such as marketing, tourism, advertising, communication and information systems. Combining advertising and education, the Challenge gives student hands-on experience in the increasingly important field of online marketing, engages them with local businesses and motivates them through the thrill of a global competition. Student teams receive US$200 in AdWords credits, Google’s premier advertising product that offers cost-per-click advertisements. The teams then recruit and work with a local business to devise an effective online marketing campaign. Students first outline a strategy, run a series of campaigns, and provide their business with recommendations to improve their online marketing. Teams submit two written reports for judging by 14 academics in eight countries. In addition, Google AdWords experts judge teams on their campaign statistics such as success metrics and account management. Rather than a marketing simulation against a computer or hypothetical marketing plans for hypothetical businesses, the Challenges has student teams develop and manage real online advertising campaigns for their clients and compete against peers globally.

Vibration of ship structures and its control

Noise and vibration in complex ship structures are becoming a prominent issue for ship building industry and ship companies due to the constant demand of building faster ships of lighter weight, and the stringent noise and libration regulation of the industry. In order to retain the full benefit of building faster ships without compromising too much on ride comfort and safety, noise and vibration control needs to be implemented. Due to the complexity of ship structures, the coupling of different wave types and multiple wave propagation paths, active control of global hull modes is difficult to implement and very expensive. Traditional passive control such as adding damping materials is only effective in the high frequency range. However, most severe damage to ship structures is caused by large structural deformation of hull structures and high dynamic stress concentration at low frequencies. The most discomfort and fatigue of passengers and the crew onboard ships is also due to the low frequency noise and vibration. Innovative approaches are therefore, required to attenuate the noise and vibration at low frequencies. This book was developed from several specialized research topics on vibration and vibration control of ship structures, mostly from the author's own PhD work at the University of Western Australia. The book aims to provide a better understanding of vibration characteristics of ribbed plate structures, plate/plate coupled structures and the mechanism governing wave propagation and attenuation in periodic and irregular ribbed structures as well as in complex ship structures. The book is designed to be a reference book for ship builders, vibro-acoustic engineers and researchers. The author also hopes that the book can stimulate more exciting future work in this area of research. It is the author's humble desire that the book can be some use for those who purchase it. This book is divided into eight chapters. Each chapter focuses on providing solution to address a particular issue on vibration problems of ship structures. A brief summary of each chapter is given in the general introduction. All chapters are inter-dependent to each other to form an integration volume on the subject of vibration and vibration control of ship structures and alike. I am in debt to many people in completing this work. In particular, I would like to thank Professor J. Pan, Dr N.H. Farag, Dr K. Sum and many others from the University of Western Australia for useful advices and helps during my times at the University and beyond. I would also like to thank my wife, Miaoling Wang, my children, Anita, Sophia and Angela Lin, for their sacrifice and continuing supports to make this work possible. Financial supports from Australian Research Council, Australian Defense Science and Technology Organization and Strategic Marine Pty Ltd at Western Australia for this work is gratefully acknowledged.

Spontaneous pacing during overground hill running

Purpose: To investigate speed regulation during overground running on undulating terrain. Methods: Following an initial laboratory session to calculate physiological thresholds, eight experienced runners completed a spontaneously paced time trial over 3 laps of an outdoor course involving uphill, downhill and level sections. A portable gas analyser, GPS receiver and activity monitor were used to collect physiological, speed and stride frequency data. Results: Participants ran 23% slower on uphills and 13.8% faster on downhills compared with level sections. Speeds on level sections were significantly different for 78.4 ± 7.0 seconds following an uphill and 23.6 ± 2.2 seconds following a downhill. Speed changes were primarily regulated by stride length which was 20.5% shorter uphill and 16.2% longer downhill, while stride frequency was relatively stable. Oxygen consumption averaged 100.4% of runner’s individual ventilatory thresholds on uphills, 78.9% on downhills and 89.3% on level sections. 89% of group level speed was predicted using a modified gradient factor. Individuals adopted distinct pacing strategies, both across laps and as a function of gradient. Conclusions: Speed was best predicted using a weighted factor to account for prior and current gradients. Oxygen consumption (VO2) limited runner’s speeds only on uphill sections, and was maintained in line with individual ventilatory thresholds. Running speed showed larger individual variation on downhill sections, while speed on the level was systematically influenced by the preceding gradient. Runners who varied their pace more as a function of gradient showed a more consistent level of oxygen consumption. These results suggest that optimising time on the level sections after hills offers the greatest potential to minimise overall time when running over undulating terrain.

The vernacular terrain : Songzhang Art Museum, Beijing, China

The field was the curation of cross-cultural new media/ digital media practices within large-scale exhibition practices in China. The context was improved understandings of the intertwining of the natural and the artificial with respect to landscape and culture, and their consequent effect on our contemporary globalised society. The research highlighted new languages of media art with respect to landscape and their particular underpinning dialects. The methodology was principally practice-led. --------- The research brought together over 60 practitioners from both local and diasporic Asian, European and Australian cultures for the first time within a Chinese exhibition context. Through pursuing a strong response to both cultural displacement and re-identification the research forged and documented an enduring commonality within difference – an agenda further concentrated through sensitivities surrounding that year’s Beijing’s Olympics. In contrast to the severe threats posed to the local dialects of many of the world’s spoken and written languages the ‘Vernacular Terrain’ project evidenced that many local creative ‘dialects’ of the environment-media art continuum had indeed survived and flourished. --------- The project was co-funded by the Beijing Film Academy, QUT Precincts, IDAProjects and Platform China Art Institute. A broad range of peer-reviewed grants was won including from the Australia China Council and the Australian Embassy in China. Through invitations from external curators much of the work then traveled to other venues including the Block Gallery at QUT and the outdoor screens at Federation Square, Melbourne. The Vernacular Terrain catalogue featured a comprehensive history of the IDA project from 2000 to 2008 alongside several major essays. Due to the reputation IDA Projects had established, the team were invited to curate a major exhibition showcasing fifty new media artists: The Vernacular Terrain, at the prestigious Songzhang Art Museum, Beijing in Dec 07-Jan 2008. The exhibition was designed for an extensive, newly opened gallery owned by one of China's most important art historians Li Xian Ting. This exhibition was not only this gallery’s inaugural non-Chinese curated show but also the Gallery’s first new media exhibition. It included important works by artists such as Peter Greenway, Michael Roulier, Maleonn and Cui Xuiwen. --------- Each artist was chosen both for a focus upon their own local environmental concerns as well as their specific forms of practice - that included virtual world design, interactive design, video art, real time and manipulated multiplayer gaming platforms and web 2.0 practices. This exhibition examined the interconnectivities of cultural dialogue on both a micro and macro scale; incorporating the local and the global, through display methods and design approaches that stitched these diverse practices into a spatial map of meanings and conversations. By examining the contexts of each artist’s practice in relationship to the specificity of their own local place and prevailing global contexts the exhibition sought to uncover a global vernacular. Through pursuing this concentrated anthropological direction the research identified key themes and concerns of a contextual language that was clearly underpinned by distinctive local ‘dialects’ thereby contributing to a profound sense of cross-cultural association. Through augmentation of existing discourse the exhibition confirmed the enduring relevance and influence of both localized and globalised languages of the landscape-technology continuum.

Correlating vehicle forces and track profile

A research project was conducted at Queensland University of Technology on the relationship between the forces at the wheel-rail interface in track and the rate of degradation of track. Data for the study was obtained from an instrumented vehicle which ran repeatedly over a section of Queensland Rail's track in Central Queensland over a 6-month period. The wheel-rail forces had to be correlated with the elements of roughness in the test track profile, which were measured with a variety of equipment. At low frequencies, there was strong correlation between forces and profile, as expected, but diminishing correlation as frequencies increased.

Peer assisted study sessions

My journey with Peer Assisted Study Sessions, or Supplemental Instruction (SI), began in 1993 when I took over a 1st year, 1st semester unit in QUT's Bachelor of Engineering program. The unit had 500 enrolments with students from all 10 engineering majors at QUT. The 500 students received a 2 hour lecture and a 1 hour tutorial per week, usually run by academic staff or postgraduate students. The unit covered basic mechanics, which comprises a challenging set of topics on how forces interact with various bodies. One normally expects 1st year students to find it difficult to come to grips with the material. However, when I ran that unit in 1993, the failure rate had been usually around 50%.

PIPP #1 - Pedestrian Interaction Patch Project

The Pedestrian Interaction Patch Project (PIPP) seeks to exert influence over and encourage abnormal pedestrian behavior. By placing an unadvertised (and non recording) interactive video manipulation system and projection source in a high traffic public area, the PIPP allows pedestrians to privately (and publically) re-engage with a previously inactive physical environment, like a commonly used walkway or corridor. This system, the results of which are projected in real time on the architectural surface, inadvertently provides pedestrians with questions around preconceived notions of self and space. In an attempt to re-activate our relationship with the physical surrounds we occupy each day the PIPP creates a new set of memories to be recalled as we re-enter known environments once PIPP has moved on and as such re-enlivens our relationship with the everyday architecture we stroll past everyday. The PIPP environment is controlled using the software program Isadora, devised by Mark Coniglio at Troika Ranch, and contains a series of video manipulation patches that are designed to not only grab the pedestrians attention but to also encourage a sense of play and interaction between the architecture, the digital environment, the initially unsuspecting participant(s) and the pedestrian audience. The PIPP was included as part of the planned walking tour for the “Playing in Urban Spaces” seminar day, and was an installation that ran for the length of the symposium in a reclaimed pedestrian space that was encountered by both the participants and general public during the course of the day long event. Ideally once discovered PIPP encouraged pedestrians to return through the course of the seminar day to see if the environmental patches had changed or altered, and changed their standard route to include the PIPP installation or to avoid it, either way, encouraging an active response to the pathways normally traveled or newly discovered each day.