Using DNA as a drug - bioprocessing and delivery strategies

DNA may take a leading role in a future generation of blockbuster therapeutics. DNA has inherent advantages over other biomolecules such as protein, RNA and virus-like particles including safety, production simplicity and higher stability at ambient temperatures. Vaccination is the principal measure for preventing influenza and reducing the impact of pandemics; however, vaccines take up to 8-9 months to produce, and the global production capacity is woefully low. With production times as short as 2 weeks, improved safety and stability, bioprocess engineering developments, and the ability to perform numerous therapeutic roles, DNA has the potential to meet the demands of emerging and existing diseases. DNA is experiencing sharp growths in demand as indicated by its use in gene therapy trials and DNA vaccine related patents. Of particular interest for therapeutic use is plasmid DNA (pDNA), a form of non-genomic DNA that makes use of cellular machinery to express proteins or antigens. The production stages of fermentation and downstream purification are considered in this article. Forward looking approaches to purifying and delivering DNA are reported, including affinity chromatography and nasal inhalation. The place that pDNA may take in the preparation for and protection against pandemics is considered. If DNA therapeutics and vaccines prove to be effective, the ultimate scale of production will be huge which shall require associated bioprocess engineering research and development for purification of this large, unique biomolecule.

Cytokine secretion in macrophages : SNAREs, Rabs and membrane trafficking

Macrophages have the capacity to rapidly secrete a wide range of inflammatory mediators that influence the development and extent of an inflammatory response. Newly synthesized and/or preformed stored cytokines and other inflammatory mediators are released upon stimulation, the timing, and volume of which is highly regulated. To finely tune this process, secretion is regulated at many levels; at the level of transcription and translation and post-translationally at the endoplasmic reticulum (ER), Golgi, and at or near the cell surface. Here, we discuss recent advances in deciphering these cytokine pathways in macrophages, focusing on recent discoveries regarding the cellular machinery and mechanisms implicated in the synthesis, trafficking, and secretion of cytokines. The specific roles of trafficking machinery including chaperones, GTPases, cytoskeletal proteins, and SNARE membrane fusion proteins will be discussed.

All about that base : differing player experiences in video game genres and the unique case of MOBA games

Video games provide unique interactive player experiences (PX) often categorised into different genres. Prior research has looked at different game genres, but rarely through a PX lens. Especially, PX in the emerging area of massive online battle arena (MOBA) games is not well understood by researchers in the field. We address this knowledge gap by presenting a PX study of different game genres, which we followed up with a second semi-structured interview study about PX in MOBA games. Among the results of our analyses are that games that are likely played with other players, such as MOBA games, stimulate less immersion and presence for players. Additionally, while challenge and frustration are significantly higher in this genre, players get a sense of satisfaction from teamwork, competition and mastery of complex gameplay interactions. Our study is the first to contribute a comprehensive insight into key motivators of MOBA players and how PX in this genre is different from other genres.

The Fleet Store : devising a public retail exhibition to promote creative, innovative and sustainable business models for emerging fashion designers

1.Description of the Work The Fleet Store was devised as a creative output to establish an exhibition linked to a fashion business model where emerging designers were encouraged to research new and innovative strategies for creating design-driven and commercial collections for a public consumer. This was a project that was devised to break down the perceptions of emerging fashion designers that designing commercial collections linked to a sustainable business model is a boring and unnecessary process. The focus was to demystify the business of fashion and to link its importance to a design-driven and public outcome that is more familiar to fashion designers. The criterion for participation was that all designers had to be registered as a business with the Australian Taxation Office. Designers were chosen from the Creative Enterprise Australia Fashion Business Incubator, the QUT fashion graduate alumni and current QUT fashion design and double degree (fashion and business) students with existing businesses. The project evolved from a series of collaborative workshops where designers were introduced to new and innovative creative industries’ business models and the processes, costings and timings involved to create a niche, sustainable business for a public exhibition of design-driven commercial collections. All designers initiated their own business infra-structure but were then introduced to the concept of collaboration for successful and profitable exhibition and business outcomes. Collaborative strategies such as crowd funding, crowd sourcing, peer to peer mentoring and manufacturing were all researched, and strategies for the establishment of the retail exhibition were all devised in a collaborative environment. All participants also took on roles outside their ‘designer’ background to create a retail exhibition that was creative but also had critical mass and aesthetic for the consumer. The Fleet Store ‘popped up’ for 2 weeks (10 days), in a heritage-listed building in an inner city location. Passers-by were important, but the main consumer was enlisted by the use of interest and investment from crowd sourcing, crowd funding, ethical marketing, corporate social responsibility projects and collaborative public relations and social media strategies. The research has furthered discussion on innovative strategies for emerging fashion designers to initiate and maintain sustainable businesses and suggests that collaboration combined with a design-driven and business focus can create a sustainable and economically viable retail exhibition. 2. Research Statement Research Background The research field involved developing a new ethical, design-driven, collaborative and sustainable model for fashion design practice and management. The research asked can a public, design-driven, collaborative retail exhibition create a platform for promoting creative, innovative and sustainable business models for emerging fashion designers. The methodology was primarily practice-led as all participants were designers in their own right and the project manager acted as a mentor and curator to guide the process and analyse the potential of the research question. The Fleet Store offers new knowledge in design practice and management; with the creation of a model where design outcomes and business models are inextricably linked to the success of the creative output. Key innovations include extending the commercialisation of emerging fashion businesses by creating a curated retail gallery for collaborative and sustainable strategies to support niche fashion designer labels. This has contributed to a broader conversation on how to nurture and sustain competitive Australian fashion designers/labels. Research Contribution and Significance The Fleet Store has contributed to a growing body of research into innovative and sustainable business models for niche fashion and creative industries’ practitioners. All participants have maintained their business infra-structure and many are currently growing their businesses, using the strategies tested for the Fleet Store. The exhibition space was visited by over 1,000 people and sales of $27,000 were made in 10 days of opening. (Follow up sales of $3,000 has also been reported.) Three of the designers were ‘discovered’ from the exhibition and have received substantial orders from high profile national buyers and retailers for next season delivery. Several participants have since collaborated to create other pop up retail environments and are now mentoring other emerging designers on the significance of a collaborative retail exhibition to consolidate niche business models for emerging fashion designers.

A review on prognostic techniques for non-stationary and non-linear rotating systems

The field of prognostics has attracted significant interest from the research community in recent times. Prognostics enables the prediction of failures in machines resulting in benefits to plant operators such as shorter downtimes, higher operation reliability, reduced operations and maintenance cost, and more effective maintenance and logistics planning. Prognostic systems have been successfully deployed for the monitoring of relatively simple rotating machines. However, machines and associated systems today are increasingly complex. As such, there is an urgent need to develop prognostic techniques for such complex systems operating in the real world. This review paper focuses on prognostic techniques that can be applied to rotating machinery operating under non-linear and non-stationary conditions. The general concept of these techniques, the pros and cons of applying these methods, as well as their applications in the research field are discussed. Finally, the opportunities and challenges in implementing prognostic systems and developing effective techniques for monitoring machines operating under non-stationary and non-linear conditions are also discussed.

Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Zombies on the road: A holistic design approach to balancing gamification and safe driving

This paper explores novel driving experiences that make use of gamification and augmented reality in the car. We discuss our design considerations, which are grounded in road safety psychology and video game design theory. We aim to address the tension between safe driving practices and player engagement. Specifically, we propose a holistic, iterative thinking process inspired by game design cognition and share our insights generated through the application of this process. We present preliminary game concepts that blend digital components with physical elements from the driving environment. We further highlight how this design process helped us to iteratively evolve these concepts towards being safer while maintaining fun. These insights and game design cognition itself will be useful to the AutomotiveUI community investigating similar novel driving experiences.

Reconstruction of a multi-vent kimberlite eruption from deposit and host rock characteristics: Jericho kimberlite, Nunavut, Canada

The Jericho kimberlite (173.1. ±. 1.3. Ma) is a small (~. 130. ×. 70. m), multi-vent system that preserves products from deep (>. 1. km?) portions of kimberlite vents. Pit mapping, drill core examination, petrographic study, image analysis of olivine crystals (grain size distributions and shape studies), and compositional and mineralogical studies, are used to reconstruct processes from near-surface magma ascent to kimberlite emplacement and alteration. The Jericho kimberlite formed by multiple eruptions through an Archean granodiorite batholith that was overlain by mid-Devonian limestones ~. 1. km in thickness. Kimberlite magma ascended through granodiorite basement by dyke propagation but ascended through limestone, at least in part, by locally brecciating the host rocks. After the first explosive breakthrough to surface, vent deepening and widening occurred by the erosive forces of the waxing phase of the eruption, by gravitationally induced failures as portions of the vent margins slid into the vent and, in the deeper portions of the vent (>. 1. km), by scaling, as thin slabs burst from the walls into the vent. At currently exposed levels, coherent kimberlite (CK) dykes (<. 40. cm thick) are found to the north and south of the vent complex and represent the earliest preserved in-situ products of Jericho magmatism. Timing of CK emplacement on the eastern side of the vent complex is unclear; some thick CK (15-20. m) may have been emplaced after the central vent was formed. Explosive eruptive products are preserved in four partially overlapping vents that are roughly aligned along strike with the coherent kimberlite dyke. The volcaniclastic kimberlite (VK) facies are massive and poorly sorted, with matrix- to clast-supported textures. The VK facies fragmented by dry, volatile-driven processes and were emplaced by eruption column collapse back into the volcanic vents. The first explosive products, poorly preserved because of partial destruction by later eruptions, are found in the central-east vent and were formed by eruption column collapse after the vent was largely cleared of country rock debris. The next active vent was either the north or south vent. Collapse of the eruption column, linked to a vent widening episode, resulted in coeval avalanching of pipe margin walls into the north vent, forming interstratified lenses of country rock-rich boulder breccias in finer-grained volcaniclastic kimberlite. South vent kimberlite has similar characteristics to kimberlite of the north vent and likely formed by similar processes. The final eruptive phase formed olivine-rich and moderately sorted deposits of the central vent. Better sorting is attributed to recycling of kimberlite debris by multiple eruptions through the unconsolidated volcaniclastic pile and associated collapse events. Post-emplacement alteration varies in intensity, but in all cases, has overprinted the primary groundmass and matrix, in CK and VK, respectively. Erosion has since removed all limestone cover.

Sensors and control for mining robotics

This paper discusses some of the sensing technologies and control approaches available for guiding robot manipulators for a class of underground mining tasks including drilling jumbos, bolting arms, shotcreters or explosive chargers. Data acquired with such sensors, in the laboratory and underground, is presented.

New insights from IODP Expedition 340 offshore Montserrat: First drilling of large volcanic island landslides

Montserrat now provides one of the most complete datasets for understanding the character and tempo of hazardous events at volcanic islands. Much of the erupted material ends up offshore, and this offshore record may be easier to date due to intervening hemiplegic sediments between event beds. The offshore dataset includes the first scientific drilling of volcanic island landslides during IODP Expedition 340, together with an unusually comprehensive set of shallow sediment cores and 2-D and 3-D seismic surveys. Most recently in 2013, Remotely Operated Vehicle (ROV) dives mapped and sampled the surface of the main landslide deposits. This contribution aims to provide an overview of key insights from ongoing work on IODP Expedition 340 Sites offshore Montserrat.Key objectives are to understand the composition (and hence source), emplacement mechanism (and hence tsunami generation) of major landslides, together with their frequency and timing relative to volcanic eruption cycles. The most recent major collapse event is Deposit 1, which involved ~1.8 km cubed of material and produced a blocky deposit at ~12-14ka. Deposit 1 appears to have involved not only the volcanic edifice, but also a substantial component of a fringing bioclastic shelf, and material locally incorporated from the underlying seafloor. This information allows us to test how first-order landslide morphology (e.g. blocky or elongate lobes) is related to first-order landslide composition. Preliminary analysis suggests that Deposit 1 occurred shortly before a second major landslide on the SW of the island (Deposit 5). It may have initiated English's Crater, but was not associated with a major change in magma composition. An associated turbidite-stack suggests it was emplaced in multiple stages, separated by at least a few hours and thus reducing the tsunami magnitude. The ROV dives show that mega-blocks in detail comprise smaller-scale breccias, which can travel significant distances without complete disintegration. Landslide Deposit 2 was emplaced at ~130ka, and is more voluminous (~8.4km cubed). It had a much more profound influence on the magmatic system, as it was linked to a major explosive mafic eruption and formation of a new volcanic centre (South Soufriere Hills) on the island. Site U1395 confirms a hypothesis based on the site survey seismic data that Deposit 2 includes a substantial component of pre-existing seafloor sediment. However, surprisingly, this pre-existing seafloor sediment in the lower part of Deposit 2 at Site U1395 is completely undeformed and flat lying, suggesting that Site U1395 penetrated a flat lying block. Work to date material from the upper part of U1396, U1395 and U1394 will also be summarised. This work is establishing a chronostratigraphy of major events over the last 1 Ma, with particularly detailed constraints during the last ~250ka. This is helping us to understand whether major landslides are related to cycles of volcanic eruptions.

Flow evaluation and hemolysis analysis of BVAD centrifugal blood pump by computational fluids dynamics

Computational fluid dynamics (CFD) and particle image velocimetry (PIV) are commonly used techniques to evaluate the flow characteristics in the development stage of blood pumps. CFD technique allows rapid change to pump parameters to optimize the pump performance without having to construct a costly prototype model. These techniques are used in the construction of a bi-ventricular assist device (BVAD) which combines the functions of LVAD and RVAD in a compact unit. The BVAD construction consists of two separate chambers with similar impellers, volutes, inlet and output sections. To achieve the required flow characteristics of an average flow rate of 5 l/min and different pressure heads (left – 100mmHg and right – 20mmHg), the impellers were set at different rotating speeds. From the CFD results, a six-blade impeller design was adopted for the development of the BVAD. It was also observed that the fluid can flow smoothly through the pump with minimum shear stress and area of stagnation which are related to haemolysis and thrombosis. Based on the compatible Reynolds number the flow through the model was calculated for the left and the right pumps. As it was not possible to have both the left and right chambers in the experimental model, the left and right pumps were tested separately.

Document timespan normalisation and understanding temporality for clinical records search

Previous qualitative research has highlighted that temporality plays an important role in relevance for clinical records search. In this study, an investigation is undertaken to determine the effect that the timespan of events within a patient record has on relevance in a retrieval scenario. In addition, based on the standard practise of document length normalisation, a document timespan normalisation model that specifically accounts for timespans is proposed. Initial analysis revealed that in general relevant patient records tended to cover a longer timespan of events than non-relevant patient records. However, an empirical evaluation using the TREC Medical Records track supports the opposite view that shorter documents (in terms of timespan) are better for retrieval. These findings highlight that the role of temporality in relevance is complex and how to effectively deal with temporality within a retrieval scenario remains an open question.

Programming: Reading, writing and reversing

In this paper, we look at the concept of reversibility, that is, negating opposites, counterbalances, and actions that can be reversed. Piaget identified reversibility as an indicator of the ability to reason at a concrete operational level. We investigate to what degree novice programmers manifest the ability to work with this concept of reversibility by providing them with a small piece of code and then asking them to write code that undoes the effect of that code. On testing entire cohorts of students in their first year of learning to program, we found an overwhelming majority of them could not cope with such a concept. We then conducted think aloud studies of novices where we observed them working on this task and analyzed their contrasting abilities to deal with it. The results of this study demonstrate the need for better understanding our students' reasoning abilities, and a teaching model aimed at that level of reality.

Evolution of a ~2.7 Ga large igneous province: A volcanological, geochemical and geochronological study of the Agnew Greenstone Belt, and new regional correlations for the Kalgoorlie Terrane (Yilgarn Craton, Western Australia)

The thick package of ~2.7 Ga mafic and ultramafic lavas and intrusions preserved among the Neoarchean of the Kalgoorlie Terrene in Western Australia provides valuable insight into geological processes controlling the most prodigious episode of growth and preservation of juvenile continental crust in Earth’s history. Limited exposure of these rocks results in uncertainty about their age, physical and chemical characteristics, and stratigraphic relationships. This in turn prevents confident correlation of regional occurrences of mafic and ultramafic successions (both intrusive and extrusive) and hinders the interpretation of tectonic setting and magmatic evolution. A recent stratigraphic drilling program of the Neoarchean stratigraphy of the Agnew Greenstone Belt in Western Australia has provided continuous exposures through a c. 7 km thick sequence of mafic and ultramafic units. In this study, we present a volcanological, lithogeochemical and chronological study of the Agnew Greenstone Belt, and provide the first pre-2690 Ma regional correlation across the Kalgoorlie Terrane. The Agnew Greenstone Belt records ~30 m.y. of episodic ultramafic-mafic magmatism that includes two cycles, each defined by a komatiite that is overlain by units that become more evolved and contaminated with time. The sequence is divided into nine conformable packages, each consisting of stacked subaqueous lava flows and comagmatic intrusions, as well as two sills without associated extrusions. Lavas, with the exception of intercalations between two units, form a layer-cake stratigraphy and were likely erupted from a system of fissures tapping the same magma source. The komatiites are not contaminated by continental crust ([La/Sm]PM ~0.7) and are of the Al-undepleted Munro-type. Crustal contamination is evident in many units (Songvang Basalt, Never Can Tell Basalt, Redeemer Basalt, and Turrett Dolerite), as judged by [La/Sm]>1, negative Nb and Ti anomalies, and geochemical mixing trends towards felsic contaminants. Crystal fractionation was also significant, with early olivine and chromite (Mg#>65) followed by plagioclase and clinopyroxene removal (Mg<65), and in the most evolved case, titanomagnetite accumulation. Three new TIMS dates on granophyric zones of mafic sills and one ICP-MS date from an interflow felsic tuff are presented and used for regional stratigraphic correlation. Cycle I magmatism began at ~2720 Ma and ended ~2705 Ma, whereas cycle II began ~2705 Ma and ended at 2690.7±1.2 Ma. Regional correlations indicate the western Kalgoorlie Terrane consists of a remarkably similar stratigraphy that can be recognised at Agnew, Ora Banda and Coolgardie, whereas the eastern part of the terrane (e.g., Kambalda Domain) does not include cycle I, but correlates well with cycle II. This research supports an autochthonous model of greenstone formation, in which one large igneous province, represented by two complete cycles, is constructed on sialic crust. New stratigraphic correlations for the Kalgoorlie Terrane indicate that many units can be traced over distances >100 km, which has implications for exploration targeting for stratigraphically hosted ultramafic Ni and VMS deposits.