Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

Scheimpflug imaging of the post lens tear film during contact lens wear

A new imaging methodology is described to visualise the post lens tear film (PLTF) during contact lens wear. A rotating-Scheimpflug camera in combination with sodium fluorescein allows evaluation of the PLTF for different contact lens modalities, including mini-scleral, rigid gas permeable (RGP) and soft contact lenses. This imaging technique provides an extension of the instrument’s current functionality. The potential advantages and limitations of the technique are discussed.

Festival focus : Brisbane International Film Festival

In 2012, the Brisbane International Film Festival officially came of age, celebrating its twenty-first birthday. The festival has emerged from a tumultuous adolescence and redefined its position on the Australian festival circuit as an advocate of locally made films and documentary filmmaking in particular. Brisbane’s International Film Festival opened in 1992 and has since been attended by more than 400,000 filmgoers. The festival is held annually and showcases a diverse range of feature films, documentaries, short films, animation and experimental work, children’s films and retrospectives.

'It's Africa. It's Arizona. It's Antarctica. It's Afghanistan. Actually, it's Alberta' : Marketing locations to film producers

This chapter begins by outlining the dynamics of contemporary international film production and the inherent tension between ‘design interest’ and ‘location interest’. A history of the promotion of particular places as filmmaking locations (including Hollywood) is presented, prior to the establishment of the first film commissions. The creation of international associations and their role in professionalization, norm setting and the standardization of offerings and activities, is then described. The chapter concludes with a discussion of commissions’ work, the emergent discourse of ‘film friendliness,’ and the differences between location marketing and other kinds of destination marketing.

Sydney's media cluster: Continuity and change in film and television

A significant media city globally , Sydney is the production and design centre for the Australian media system and a subsidiary node of larger international systems principally headquartered in Los Angeles and London. Its media cluster is undergoing transformations to improve its position internationally by increasing capabilities and ties to other Australian and international production clusters. Sydney’s media cluster is a collection of suburbs forming an “arc” along major transport corridors stretching from Macquarie Park in the north to Sydney airport in the south. As a dispersed rather than tightly bound cluster, it is defined by the functional proximity provided by automobile and telecommunication networks Sydney’s media cluster is considered here along two dimensions—that of Sydney’s place within the ecology of Australian and international media and that of its internal organization within the geographical space of metropolitan Sydney. The first examines Sydney’s media cluster at the level of the metropolitan area of Sydney within its state, national and international contexts; while the second digs below this level to explore its working out in urban space.

Cyclic Salinity Model for deposition of large-scale coal deposits

Existing field data for Rangal coals (Late Permian) of the Bowen Basin, Queensland, Australia, are inconsistent with the depositional model generally accepted in the current geological literature to explain coal deposition. Given the apparent unsuitability of the current depositional model to the Bowen Basin coal data, a new depositional model, here named the Cyclic Salinity Model, is proposed and tested in this study.

Influence of pipe length and flow rate on nano-particle deposition in laminar circular pipe flows

The Lagrangian particle tracking provides an effective method for simulating the deposition of nano- particles as well as micro-particles as it accounts for the particle inertia effect as well as the Brownian excitation. However, using the Lagrangian approach for simulating ultrafine particles has been limited due to computational cost and numerical difficulties. The aim of this paper is to study the deposition of nano-particles in cylindrical tubes under laminar condition using the Lagrangian particle tracking method. The commercial Fluent software is used to simulate the fluid flow in the pipes and to study the deposition and dispersion of nano-particles. Different particle diameters as well as different pipe lengths and flow rates are examined. The results show good agreement between the calculated deposition efficiency and different analytic correlations in the literature. Furthermore, for the nano-particles with higher diameters and when the effect of inertia has a higher importance, the calculated deposition efficiency by the Lagrangian method is less than the analytic correlations based on Eulerian method due to statistical error or the inertia effect.

The Down Under book and film remind us our copyright law’s still unfair for artists

Australian copyright law is broken, and the Australian Government isn’t moving quickly to fix it. Borrowing, quoting, and homage are fundamental to the creative process. This is how people are inspired to create. Under Australian law, though, most borrowing is copyright infringement, unless it is licensed or falls within particular, narrow categories. This year marks five years since the very real consequences of Australia’s restrictive copyright law for Australian artists were made clear in the controversial litigation over Men at Work’s 1981 hit Down Under. The band lost a court case in 2010 that found that the song’s iconic flute riff copied some of the 1934 children’s song Kookaburra Sits in the Old Gumtree. A new book and documentary tell us more about the story behind the anthem – and the court case. The book, Down Under by Trevor Conomy, and the documentary, You Better Take Cover by Harry Hayes, bring renewed interest and new perspectives on the tragic story.

Distribution Revolution: Conversations about the Digital Future of Film and Television

Distribution Revolution is a collection of interviews with leading film and TV professionals concerning the many ways that digital delivery systems are transforming the entertainment business. These interviews provide lively insider accounts from studio executives, distribution professionals, and creative talent of the tumultuous transformation of film and TV in the digital era. The first section features interviews with top executives at major Hollywood studios, providing a window into the big-picture concerns of media conglomerates with respect to changing business models, revenue streams, and audience behaviors. The second focuses on innovative enterprises that are providing path-breaking models for new modes of content creation, curation, and distribution—creatively meshing the strategies and practices of Hollywood and Silicon Valley. And the final section offers insights from creative talent whose professional practices, compensation, and everyday working conditions have been transformed over the past ten years. Taken together, these interviews demonstrate that virtually every aspect of the film and television businesses is being affected by the digital distribution revolution, a revolution that has likely just begun. Interviewees include: • Gary Newman, Chairman, 20th Century Fox Television • Kelly Summers, Former Vice President, Global Business Development and New Media Strategy, Walt Disney Studios • Thomas Gewecke, Chief Digital Officer and Executive Vice President, Strategy and Business Development, Warner Bros. Entertainment • Ted Sarandos, Chief Content Officer, Netflix • Felicia D. Henderson, Writer-Producer, Soul Food, Gossip Girl • Dick Wolf, Executive Producer and Creator, Law & Order

Location and labor: Critical crossroads in global film and television

I approached the editorial prompt as an opportunity to work through some of the concerns driving my current research on creative labor in emergent or ‘peripheral’ media hubs, centers of production activity outside established media capitals that are nevertheless increasingly integrated into a global production apparatus. It builds from my research on the role that film, television and digital media production have played in the economic and cultural strategies of Glasgow, Scotland, and extends the focus on media work to other locations, including Prague and Budapest. I am particularly drawn to the spatial dynamics at play in these locations and how local producers, writers, directors and crew negotiate a sense of place and creative identity against the flows and counter-flows of capital and culture. This means not only asking questions about the growing ensemble of people, places, firms and policies that make international productions possible, but also studying the more quotidian relationships between media workers and the locations (both near and far) where they now find work. I do not see these tasks as unrelated. On the one hand, such queries underscore how international production depends on a growing constellation of interchangeable parts and is facilitated by various actors whose agendas may or may not converge. On the other hand, these questions also betray an even more complicated dynamic, a process that is shifting the spatial orientation of both location and labor around uneven and contested scales. As local industries reimagine themselves as global players, media practitioners are caught up in a new geography of creative labor: not only are personnel finding it increasingly necessary to hop from place to place to follow the work, but also place itself is changing, as locations morph into nebulous amalgamations of tax rebates, subsidized facilities, production services and (when it still matters) natural beauty.

Anthropogenic nitrogen deposition predicts local grassland primary production worldwide

Humans dominate many important Earth system processes including the nitrogen (N) cycle. Atmospheric N deposition affects fundamental processes such as carbon cycling, climate regulation, and biodiversity, and could result in changes to fundamental Earth system processes such as primary production. Both modelling and experimentation have suggested a role for anthropogenically altered N deposition in increasing productivity, nevertheless, current understanding of the relative strength of N deposition with respect to other controls on production such as edaphic conditions and climate is limited. Here we use an international multiscale data set to show that atmospheric N deposition is positively correlated to aboveground net primary production (ANPP) observed at the 1-m2 level across a wide range of herbaceous ecosystems. N deposition was a better predictor than climatic drivers and local soil conditions, explaining 16% of observed variation in ANPP globally with an increase of 1 kg N·ha-1·yr-1 increasing ANPP by 3%. Soil pH explained 8% of observed variation in ANPP while climatic drivers showed no significant relationship. Our results illustrate that the incorporation of global N deposition patterns in Earth system models are likely to substantially improve estimates of primary production in herbaceous systems. In herbaceous systems across the world, humans appear to be partially driving local ANPP through impacts on the N cycle.

Verification and Operation of Adaptive Materials in Space

Piezoelectric polymers based on polyvinylidene fluoride (PVDF) are of interest as smart materials for novel space-based telescope applications. Dimensional adjustments of adaptive thin polymer films are achieved via controlled charge deposition. Predicting their long-term performance requires a detailed understanding of the piezoelectric property changes that develop during space environmental exposure. The overall materials performance is governed by a combination of chemical and physical degradation processes occurring in low Earth orbit as established by our past laboratory-based materials performance experiments (see report SAND 2005-6846). Molecular changes are primarily induced via radiative damage, and physical damage from temperature and atomic oxygen exposure is evident as depoling, loss of orientation and surface erosion. The current project extension has allowed us to design and fabricate small experimental units to be exposed to low Earth orbit environments as part of the Materials International Space Station Experiments program. The space exposure of these piezoelectric polymers will verify the observed trends and their degradation pathways, and provide feedback on using piezoelectric polymer films in space. This will be the first time that PVDF-based adaptive polymer films will be operated and exposed to combined atomic oxygen, solar UV and temperature variations in an actual space environment. The experiments are designed to be fully autonomous, involving cyclic application of excitation voltages, sensitive film position sensors and remote data logging. This mission will provide critically needed feedback on the long-term performance and degradation of such materials, and ultimately the feasibility of large adaptive and low weight optical systems utilizing these polymers in space.

Numerical investigation of aerosol particle transport and deposition in realistic lung airway

Different human activities like combustion of fossil fuels, biomass burning, industrial and agricultural activities, emit a large amount of particulates into the atmosphere. As a consequence, the air we inhale contains significant amount of suspended particles, including organic and inorganic solids and liquids, as well as various microorganism, which are solely responsible for a number of pulmonary diseases. Developing a numerical model for transport and deposition of foreign particles in realistic lung geometry is very challenging due to the complex geometrical structure of the human lung. In this study, we have numerically investigated the airborne particle transport and its deposition in human lung surface. In order to obtain the appropriate results of particle transport and deposition in human lung, we have generated realistic lung geometry from the CT scan obtained from a local hospital. For a more accurate approach, we have also created a mucus layer inside the geometry, adjacent to the lung surface and added all apposite mucus layer properties to the wall surface. The Lagrangian particle tracking technique is employed by using ANSYS FLUENT solver to simulate the steady-state inspiratory flow. Various injection techniques have been introduced to release the foreign particles through the inlet of the geometry. In order to investigate the effects of particle size on deposition, numerical calculations are carried out for different sizes of particles ranging from 1 micron to 10 micron. The numerical results show that particle deposition pattern is completely dependent on its initial position and in case of realistic geometry; most of the particles are deposited on the rough wall surface of the lung geometry instead of carinal region.