Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer

Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life.

Food and interaction design [Extended Abstract]

Food and interaction design presents an interesting challenge to the HCI community in attending to the pervasive nature of food, the socio-cultural differences in food practices and a changing global foodscape. To design for meaningful and positive interactions it is essential to identify daily food practices and the opportunities for the design of technology to support such practices. This workshop brings together a community of researchers and practitioners in human-food interaction to attend to the practical and theoretical difficulties in designing for human-food interactions in everyday life. Through a practical field study and workshop we explore themes of food experiences, health and wellbeing, sustainability and alternative food cultures.

Human–computer interaction : the impact of users’ cognitive styles on query reformulation behaviour during web searching

This paper discusses users’ query reformulation behaviour while searching information on the Web. Query reformulations have emerged as an important component of Web search behaviour and human-computer interaction (HCI) because a user’s success of information retrieval (IR) depends on how he or she formulates queries. There are various factors, such as cognitive styles, that influence users’ query reformulation behaviour. Understanding how users with different cognitive styles formulate their queries while performing Web searches can help HCI researchers and information systems (IS) developers to provide assistance to the users. This paper aims to examine the effects of users’ cognitive styles on their query reformation behaviour. To achieve the goal of the study, a user study was conducted in which a total of 3613 search terms and 872 search queries were submitted by 50 users who engaged in 150 scenario-based search tasks. Riding’s (1991) Cognitive Style Analysis (CSA) test was used to assess users’ cognitive style as wholist or analytic, and verbaliser or imager. The study findings show that users’ query reformulation behaviour is affected by their cognitive styles. The results reveal that analytic users tended to prefer Add queries while all other users preferred New queries. A significant difference was found among wholists and analytics in the manner they performed Remove query reformulations. Future HCI researchers and IS developers can utilize the study results to develop interactive and user-cantered search model, and to provide context-based query suggestions for users.

Identifying familiarity to facilitate intuitive interaction for older adults

Almost every nation on the planet is experiencing increases in both the number and proportion of older adults. Research has shown that older adults use technology less intuitively than younger adults, and have more difficulty with using products effectively. With an ever-increasing population of older adults, it is necessary to understand why they often struggle to use technology, which is becoming more and more important in day to day living. Intuitive use of products is grounded in familiarity and prior experience. The aims of this research were twofold: (i) to examine the differences in familiarity between younger and older adults, to see if this could explain the difficulties faced by some older adults; (ii) to develop investigational methods to assist designers in identifying familiarity in prospective users. Two empirical studies were conducted. The first experiment was conducted in the field with 32 participants, divided across four age groups (18 – 44, 45 – 59, 60 – 74, and 75+). This experiment was conducted in the participants’ homes, with a product they were familiar with. Familiarity was measured through the analysis of data collected through interviews, observation and retrospective protocol. The results of this study show that the youngest group demonstrated significantly higher levels of familiarity with products they own than the 60 – 74 and the 75+ age groups. There were no significant differences between the 18 – 44 age group and the 45 – 59 age group and there were also no significant differences between the three oldest age groups. The second experiment was conducted with 32 participants, across the same four age groups. Four everyday products were used in this experiment. The results of Experiment 2 show that, with previously unused products, younger adults demonstrate significantly higher levels of familiarity than the three older age groups. The three oldest age groups had no significant differences between them. The results of these two studies show that younger adults are more familiar with contemporary products than older adults. They also demonstrate that in terms of familiarity, older adults do not differ significantly as they get older. The results also show that the 45 – 59 age group demonstrate higher levels of familiarity with products they have owned, in comparison with those they have not. The two older age groups did not demonstrate such differences. This suggests that interacting with products over time increases familiarity more for middle-aged adults than for older adults. As a result of this research, a method that can be used by designers to identify potential users’ product familiarity has been identified. This method is easy to use, quick, low cost, highly mobile, flexible, and allows for easy data collection and analysis. A tool has been designed that assists designers and researchers to use the method. Designers can use the knowledge gained from this tool, and integrate it into the design process, resulting in more intuitive products. Such products may lead to improvements in the quality of life of older adults, as a result of improved societal integration, better health management, and more widespread use of communications technology.

Intuitive interaction and older people

Older people often struggle with using contemporary products and interfaces. They show slower, less intuitive interaction with more errors. This paper reports on a large project designed to investigate why older people have these difficulties and what strategies could be used to mitigate them. The project team found that older people are less familiar with products that they own than younger ones, while both older and middle aged people are less familiar with products that they do not own than younger ones. Age related cognitive decline is also related to slower and less intuitive performance with contemporary products and interfaces. Therefore, the reasons behind the problems that older people demonstrate with contemporary technologies involve a mix of familiarity and capability. Redundancy applied to an interface in the form of symbols and words is helpful for middle aged and younger old people but the oldest age group performed better with a words only interface. Also, older people showed faster and more intuitive use with a flat interface than a nested one, although there was no difference in errors. Further work is ongoing in order to establish ways in which these findings can be usefully applied in the design process.

Multi-cursor multi-user mobile interaction with a large shared display

When using a mobile device to control a cursor on a large shared display, the interaction must be carefully planned to match the environment and purpose of the systems use. We describe a ‘democratic jukebox’ system that revealed five recommendations that should be considered when designing this type of interaction relating to providing feedback to the user; how to represent users in a multi-cursor based system; where people tend to look and their expectation of how to move their cursor; the orientation of screens and the social context; and, the use of simulated users to give the real users a sense that they are engaging with a greater audience.

Ca2+ regulates the Drosophila Stoned-A and Stoned-B proteins interaction with the C2B domain of Synaptotagmin-1.

The dicistronic Drosophila stoned gene is involved in exocytosis and/or endocytosis of synaptic vesicles. Mutations in either stonedA or stonedB cause a severe disruption of neurotransmission in fruit flies. Previous studies have shown that the coiled-coil domain of the Stoned-A and the µ-homology domain of the Stoned-B protein can interact with the C2B domain of Synaptotagmin-1. However, very little is known about the mechanism of interaction between the Stoned proteins and the C2B domain of Synaptotagmin-1. Here we report that these interactions are increased in the presence of Ca(2+). The Ca(2+)-dependent interaction between the µ-homology domain of Stoned-B and C2B domain of Synaptotagmin-1 is affected by phospholipids. The C-terminal region of the C2B domain, including the tryptophan-containing motif, and the Ca(2+) binding loop region that modulate the Ca(2+)-dependent oligomerization, regulates the binding of the Stoned-A and Stoned-B proteins to the C2B domain. Stoned-B, but not Stoned-A, interacts with the Ca(2+)-binding loop region of C2B domain. The results indicate that Ca(2+)-induced self-association of the C2B domain regulates the binding of both Stoned-A and Stoned-B proteins to Synaptotagmin-1. The Stoned proteins may regulate sustainable neurotransmission in vivo by binding to Ca(2+)-bound Synaptotagmin-1 associated synaptic vesicles.

The interaction between exercise, appetite and food intake : implications for weight control

Exercise could indirectly affect body weight by exerting changes on various components of appetite control, including nutrient and taste preferences, meal size and frequency, and the drive to eat. This review summarizes the evidence on how exercise affects appetite and eating behavior and in particular answers the question, “Does exercise induce an increase in food intake to compensate for the increase in energy expenditure?” Evidence will be presented to demonstrate that there is no automatic increase in food intake in response to acute exercise and that the response to repeated exercise is variable. The review will also identify areas of further study required to explain the variability. One limitation with studies that assess the efficacy of exercise as a method of weight control is that only mean data are presented—the individual variability tends to be overlooked. Recent evidence highlights the importance of characterizing the individual variability by demonstrating exercise-induced changes in appetite. Individuals who experience lower than theoretically predicted reductions in body weight can be characterized by hedonic (eg, pleasure) and homeostatic (eg, hunger) features.

Tangible cultural heritage and adaptive reuse: the Old Government House, Brisbane, Australia

The Old Government House, a former residence of the Queen’s representatives in Brisbane, Australia, symbolises British cultural heritage of Colonial Queensland. Located on the campus of the Queensland University of Technology, it is one of the oldest surviving examples of a stately residence in Queensland. Built in 1860s, the Old Government House was originally intended as a temporary residence for the first governor of the newly independent colony of Queensland. However, it remained the vice-regal residence until 1909, serving eleven succeeding governors. Nearly seven decades later, it became the first building in Queensland to be protected under heritage legislation. Thus its importance, as an excellent exemplar that demonstrates the significance of cultural heritage, was established. The Old Government House has survived 150 years of restoration work, refurbishments, and additions. Through these years, it has served the people of Queensland in a multitude of roles. This paper aims to investigate the survival of heritage listed buildings through their adaptive re-use. Its focus will be on the adaptive reuse of the Old Government House through its refurbishments and additions over a period of 150 years. Through a qualitative research process this paper will endeavour to establish the significance of restoration work on the Old Government house; the new opportunities that has opened up as a result of the restoration work; the continued maintenance and management of the building through adaptive re-use; the economic benefits of restoration work; and its contribution to the on-going interest in the preservation of the Tangible Cultural Heritage.

Resilience by design: A participatory approach to designing an interactive digital application for promoting children's resilience

The promotion of resilience (the capacity of an individual or community to bounce back and recover from adversity) has become an important area of public health. In recent years it has expanded into the digital domain, and many online applications have been developed to promote children's resilience. In this study, it is argued that the majority of existing applications are limited because they take a didactic approach, and conceive of interaction as providing navigational choices. Because they simply provide information about resilience or replicate offline, scenario-based strategies, the understanding of resilience they provide is confined to a few, predetermined factors. In this study I propose a new, experiential approach to promoting resilience digitally. I define resilience as an emergent, situated and context-specific phenomenon. Using a Participatory Design model in combination with a salutogenic (strength-based) health methodology, this project has involved approximately 50 children as co-designers and co-researchers over two years. The children have contributed to the design of a new set of interactive resilience tools, which facilitate resilience promotion through dialogic and experiential learning. The major outcomes of this study include a new methodology for developing digital resilience tools, a new set of tools that have been developed and evaluated in collaboration with children and a set of design principles to guide future development. Beyond these initial and tangible outcomes, this study has also established that the benefits of introducing Participatory Design into a health promoting model rests primarily in the change of the role of children from "users" of technology and education to co-designers, where they assume a leadership role in both designing the tools and in directing their resilience learning.

A three-nucleotide mutation altering the Maize streak virus Rep pRBR-interaction motif reduces symptom severity in maize and partially reverts at high frequency without restoring pRBR-Rep binding

Geminivirus infectivity is thought to depend on interactions between the virus replication-associated proteins Rep or RepA and host retinoblastoma-related proteins (pRBR), which control cell-cycle progression. It was determined that the substitution of two amino acids in the Maize streak virus (MSV) RepA pRBR-interaction motif (LLCNE to LLCLK) abolished detectable RepA-pRBR interaction in yeast without abolishing infectivity in maize. Although the mutant virus was infectious in maize, it induced less severe symptoms than the wild-type virus. Sequence analysis of progeny viral DNA isolated from infected maize enabled detection of a high-frequency single-nucleotide reversion of C(601)A in the 3 nt mutated sequence of the Rep gene. Although it did not restore RepA-pRBR interaction in yeast, sequence-specific PCR showed that, in five out of eight plants, the C(601)A reversion appeared by day 10 post-inoculation. In all plants, the C(601)A revertant eventually completely replaced the original mutant population, indicating a high selection pressure for the single-nucleotide reversion. Apart from potentially revealing an alternative or possibly additional function for the stretch of DNA that encodes the apparently non-essential pRBR-interaction motif of MSV Rep, the consistent emergence and eventual dominance of the C(601)A revertant population might provide a useful tool for investigating aspects of MSV biology, such as replication, mutation and evolution rates, and complex population phenomena, such as competition between quasispecies and population turnover. © 2005 SGM.

Exploration and reflection in interactive art : glass pond

Glass Pond is an interactive artwork designed to engender exploration and reflection through an intuitive, tangible interface and a simulation agent. It is being developed using iterative methods. A study has been conducted with the aim of illuminating user experience, interface, design, and performance issues.The paper describes the study methodology and process of data analysis including coding schemes for cognitive states and movements. Analysis reveals that exploration and reflection occurred as well as composing behaviours (unexpected). Results also show that participants interacted to varying degrees. Design discussion includes the artwork's (novel) interface and configuration.

Contribution of DEAF1 structural domains to the interaction with the breast cancer oncogene LMO4

The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1.

Oblique-Shock-Wave/Boundary-Layer Interaction Using Near-Wall Reynolds-Stress Models

A synthesis is presented of the predictive capability of a family of near-wall wall-normal free Reynolds stress models (which are completely independent of wall topology, i.e., of the distance fromthe wall and the normal-to-thewall orientation) for oblique-shock-wave/turbulent-boundary-layer interactions. For the purpose of comparison, results are also presented using a standard low turbulence Reynolds number k–ε closure and a Reynolds stress model that uses geometric wall normals and wall distances. Studied shock-wave Mach numbers are in the range MSW = 2.85–2.9 and incoming boundary-layer-thickness Reynolds numbers are in the range Reδ0 = 1–2×106. Computations were carefully checked for grid convergence. Comparison with measurements shows satisfactory agreement, improving on results obtained using a k–ε model, and highlights the relative importance of redistribution and diffusion closures, indicating directions for future modeling work.