Chimeric aptamers in cancer cell-targeted drug delivery

Aptamers are single-stranded structured oligonucleotides (DNA or RNA) that can bind to a wide range of targets ("apatopes") with high affinity and specificity. These nucleic acid ligands, generated from pools of random-sequence by an in vitro selection process referred to as systematic evolution of ligands by exponential enrichment (SELEX), have now been identified as excellent tools for chemical biology, therapeutic delivery, diagnosis, research, and monitoring therapy in real-time imaging. Today, aptamers represent an interesting class of modern pharmaceuticals which with their low immunogenic potential mimic extend many of the properties of monoclonal antibodies in diagnostics, research, and therapeutics. More recently, chimeric aptamer approach employing many different possible types of chimerization strategies has generated more stable and efficient chimeric aptamers with aptameraptamer, aptamernonaptamer biomacromolecules (siRNAs, proteins) and aptamernanoparticle chimeras. These chimeric aptamers when conjugated with various biomacromolecules like locked nucleic acid (LNA) to potentiate their stability, biodistribution, and targeting efficiency, have facilitated the accurate targeting in preclinical trials. We developed LNA-aptamer (anti-nucleolin and EpCAM) complexes which were loaded in iron-saturated bovine lactofeerin (Fe-blf)-coated dopamine modified surface of superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs). This complex was used to deliver the specific aptamers in tumor cells in a co-culture model of normal and cancer cells. This review focuses on the chimeric aptamers, currently in development that are likely to find future practical applications in concert with other therapeutic molecules and modalities.

Development of ligand incorporated chitosan nanoparticles for the selective delivery of 5-fluorouracil to colon

Drug delivery systems with active targeting ligand provide improved therapeutic efficiency due to the selectivity towards tumor cells. In this paper we prepared drug loaded nanoparticles (NPs) using folate (FA) incorporated chitosan (FA-CS) based on ionic gelation technology. FA-CS NPs were spherical in shape with an average particle size of 100 nm, while 5-fluorouracil (5-FU) loaded NPs became less circular with average particle size of 100-500 nm. NPs made from FA-CS conjugates exhibited improved capability to encapsulate hydrophilic 5-FU. It was found 5-FU distributed in FA-CS NPs in solid solution state. In vitro release results demonstrated the release of 5-FU from FA-CS NPs was more controllable as compared to that of CS NPs.

Embedding academic skills development in course delivery

Innovative approaches need to be adopted to meet the challenge of ensuring that graduates at the end of their course of study are not only strong in their discipline, but also have the required generic skills to give them a good standing within their selected professions. This paper reports on a study that examined how well academic skills are embedded into the undergraduate Environmental Science curriculum at Deakin University in Australia. It reports on students’ self evaluation of their essay writing skills, and a case study that involves a discipline specialist working with an academic skills advisor to enhance student generic skills. It discusses the patchy nature of current implementation of programs for generic skill education.

Medial prefrontal cortex suppression of the hypothalamic–pituitary–adrenal axis response to a physical stressor, systemic delivery of interleukin-1β

Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic–pituitary–adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic–pituitary–adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1β. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic–pituitary–adrenal axis responses to systemic interleukin-1β, we next mapped the effects of similar lesions on interleukin-1β-induced Fos expression in regions previously shown to regulate the hypothalamic–pituitary–adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1β, an outcome that is difficult to reconcile with a simple medial prefrontal cortex–bed nucleus of the stria terminalis–corticotropin-releasing factor cell control circuit.

A cache-based mobility-aware scheme for real-time continuous media delivery in wireless networks

Providing real-time or continuous media (CM) application services in wireless networks poses a significant challenge, as it requires timely delivery of data in a best-effort network. In this paper, we propose a cache-based scheme for mobility-aware, CM applications. The proposed scheme exploits a previously proposed caching strategy to complement Mobile-IP by placing services closer to migrated mobile nodes. The central idea of this work is based on the migration of sessions in order to facilitate uninterrupted delivery of CM in mobile environments. The performance of the proposed scheme is investigated by simulation studies. In particular, the effect of the proposed scheme on several QoS parameters under varying conditions of mobility and CM data is measured.

Exploring new models of elite sport delivery : the case of triathlon in the USA and Australia

There is a growing body of knowledge that examines the tasks and processes for successful sport and recognizes that sport development activities undertaken within the framework of recruitment, retention, and transition should vary between sports and contexts. There has been little research that has examined newer models of sport development in emerging sports. This research examines elite sport development structure and delivery in the sport of triathlon in the USA and Australia. The research team conducted interviews with representatives responsible for the delivery and development of triathlon. The results show three overarching elements in elite sport development: (1) the sport development process, (2) the sport development setting, and (3) outsourcing delivery of sport development. Triathlon has different processes and settings for sport development between the USA and Australia. However, both countries share a core similarity in how they deliver elite sport through a third party organization. A discussion of the implications for the development of new models of elite sport development ensues.

User preference of cyber security awareness delivery methods

Operating systems and programmes are more protected these days and attackers have shifted their attention to human elements to break into the organisation's information systems. As the number and frequency of cyber-attacks designed to take advantage of unsuspecting personnel are increasing, the significance of the human factor in information security management cannot be understated. In order to counter cyber-attacks designed to exploit human factors in information security chain, information security awareness with an objective to reduce information security risks that occur due to human related vulnerabilities is paramount. This paper discusses and evaluates the effects of various information security awareness delivery methods used in improving end-users’ information security awareness and behaviour. There are a wide range of information security awareness delivery methods such as web-based training materials, contextual training and embedded training. In spite of efforts to increase information security awareness, research is scant regarding effective information security awareness delivery methods. To this end, this study focuses on determining the security awareness delivery method that is most successful in providing information security awareness and which delivery method is preferred by users. We conducted information security awareness using text-based, game-based and video-based delivery methods with the aim of determining user preferences. Our study suggests that a combined delivery methods are better than individual security awareness delivery method.

MidiCities : test beds for innovative delivery of urban transformation

Cities globally and nationally are facing a range of daunting challenges to respond to a suite of emerging imperatives including a low carbon future, oil vulnerability, demographic re-composition, and the prospect of unpredictable economic shocks. To pursue a future that is sustainable and resilient requires substantial transformation of existing urban areas and creation of new mechanisms to guide and manage delivery of physical, economic and social changes.

Mid-sized cities provide legible, nimble test beds for exploring cross-disciplinary models and innovative governance and delivery techniques. Australia’s ‘MidiCities’ – home to 4 million urban dwellers frequently overlooked by urban policy or research effort – are emerging as crucibles of innovation and experimentation. Most of these cities retain that essential key ingredient for sustainable urbanism, economic resilience and community identity: a strong, highly legible city centre with a tightly clustered diversity of facilities and functions – the multi-functional activity centre that metropolitan suburban hubs yearn to grow up to become!

These diverse MidiCities are passing a threshold of self-confident sophistication, and are now providing valuable lessons for each other, which could be adopted or adapted by metropolitan cities where scale and complexity can often overwhelm the search for new and appropriate approaches to delivery of rapid change while maintaining clear guidance toward the vision of a ‘preferred’ future. A network of professionals working with Australian and New Zealand MidiCities is coalescing toward a cross-disciplinary platform for exchange of experiences and information, mutual support, improved research and understanding, capacity-building and the refinement of new specialist skills and structures.

Decision support and the effectiveness of web-based delivery and information tailoring for bowel cancer screening : an exploratory study

Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females throughout the developed world. Population screening using fecal occult blood tests (FOBTs) facilitates early detection and greater chance of survival, but participation rates are low. We developed a Web-based decision tool to provide information tailored to an individual’s decision stage for CRC screening and attitude toward screening utilizing the Preventive Health Model (PHM) and Precaution Adoption Process Model (PAPM) as theoretical frameworks for screening behavior. We describe the practical steps employed in the tool’s design and the subsequent conduct of an exploratory study.
Objective: To design a decision tool for CRC screening and conduct an exploratory study among average-risk men and women to (1) test the impact of message type (tailored vs non-tailored) and message delivery modality (Web-based vs paper-based) on attitudes toward screening and screening uptake, and (2) investigate the acceptability of the decision tool and relevance of materials.
Methods: Participants (n = 100), recruited from a population sample of men and women aged 50-76 residing in urban Adelaide, Australia, were randomly assigned to a control group or one of 4 interventions: (1) Web-based and tailored information, (2) paper-based and tailored information, (3) Web-based and non-tailored (generic) information, or (4) paper-based and non-tailored information. Participation was augmented by snowball recruitment (n = 19). Questionnaires based on PHM variables were administered pre- and post-intervention. Participants were given the opportunity to request an FOBT. Following the intervention, participants discussed the acceptability of the tool.
Results: Full data were available for 87.4% (104/119) of participants. Post-intervention, perceived susceptibility scores for individuals receiving tailored information increased from mean 10.6 (SD 2.1) to mean 11.8 (SD 2.2). Scores on self-efficacy increased in the tailored group from mean 11.7 (SD 2.0) to mean 12.6 (SD 1.8). There were significant time x modality x message effects for social influence and salience and coherence, reflecting an increase in these scores for tailored Web-based participants only; social influence scores increased from mean 11.7 (SD 2.6) to mean 14.9 (SD 2.3), and salience and coherence scores increased from mean 16.0 (SD 2.2) to mean 17.7 (SD 2.1). There was no greater influence of modality or message type on movement toward a decision to screen or screening uptake, indicating that neither tailored messages nor a Web modality had superior effect. Overall, participants regarded tailored messages positively, but thought that the Web tool lacked “media richness.”
Conclusions: This exploratory study confirms that tailoring on PHM predictors of CRC screening has the potential to positively address attitudes toward screening. However, tailoring on these variables did not result in significantly increased screening uptake. Future research should consider other possible psychosocial influences. Mode of delivery did not affect outcomes, but as a delivery medium, the Web has economic and logistical advantages over paper.