The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan–hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5 h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8 h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8 h to 24 h post-administration compared to the free NPs, due to a NP ‘guarding’ effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24 h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.

Design expressions for the in-plane shear capacity of confined masonry shear walls containing squat panels

In-plane shear capacity formulation of reinforced masonry is commonly conceived as the sum of the capacities of three parameters, viz, the masonry, the reinforcement, and the precompression. The term “masonry” incorporates the aspect ratio of the wall without any regard to the aspect ratio of the panels inscribed (and hence confined) by the vertical and the horizontal reinforced grout cores. This paper proposes design expressions in which the aspect ratio of such panels is explicitly included. For this purpose, the grouted confining cores are regarded as a grid of confining elements within which the panels are positioned. These confined masonry panels are then considered as building blocks for multi-bay, multi-storied confined masonry shear walls and analyzed using an experimentally validated macroscopic finite-element model. Results of the analyzes of 161 confined masonry walls containing panels of height to length ratio less than 1.0 have been regressed to formulate design expressions. These expressions have been first validated using independent test data sets and then compared with the existing equations in some selected international design standards. The concept of including the unreinforced masonry panel aspect ratio as an additional term in the design expression for partially grouted/confined masonry shear walls is recommended based on the conclusions from this paper.

A new method for the in vivo identification of mechanical properties in arteries from cine MRI images: Theoretical framework and validation

Quantifying the stiffness properties of soft tissues is essential for the diagnosis of many cardiovascular diseases such as atherosclerosis. In these pathologies it is widely agreed that the arterial wall stiffness is an indicator of vulnerability. The present paper focuses on the carotid artery and proposes a new inversion methodology for deriving the stiffness properties of the wall from cine-MRI (magnetic resonance imaging) data. We address this problem by setting-up a cost function defined as the distance between the modeled pixel signals and the measured ones. Minimizing this cost function yields the unknown stiffness properties of both the arterial wall and the surrounding tissues. The sensitivity of the identified properties to various sources of uncertainty is studied. Validation of the method is performed on a rubber phantom. The elastic modulus identified using the developed methodology lies within a mean error of 9.6%. It is then applied to two young healthy subjects as a proof of practical feasibility, with identified values of 625 kPa and 587 kPa for one of the carotid of each subject.

Retention and graduation of Aboriginal and Torres Strait Islander students in initial teacher education : a review of the literature

While the need to increase numbers of Indigenous teachers has been highlighted for many years, Aboriginal and Torres Strait Islander teachers are still significantly underrepresented in Australia making up less that 1% of teachers in schools. Nationally, little has changed since the 1980s when Hughes and Wilmot (1992) called for ‘1000 Indigenous teachers by 1990’. This paper reports on an initial literature review of teacher education as related to the preparation of Aboriginal and Torres Strait Islanders. Alongside the scholarly literature, the review to date includes analysis of over twenty policy documents and government reports as well as web-based descriptions of historical and current models of Indigenous teacher education including both mainstream Education programs and cohort-based and community models. While the literature provides examples of successful models of Indigenous teacher education it also illuminates the longstanding and interrelated factors that continue to impact on the success or failure of teacher education for Aboriginal and Torres Strait Islanders

Screening for youth depression in schools : a review of the literature

This paper provides a review of the literature pertaining to screening for youth depression in schools. It provides the rationale regarding this topic – why this topic is important and needs to be explored. This justification is followed by an investigation of the importance of mental health intervention in general – including depression. Analysis will then shift to the current literature surrounding screening for youth depression in schools, followed by additional information relating to this topic.

Ecological approaches in planning for sustainable cities : a review of the literature

Rapid urbanization has brought environmentally, socially, and economically great challenges to cities and societies. To build a sustainable city, these challenges need to be faced efficiently and successfully. This paper focuses on the environmental issues and investigates the ecological approaches for planning sustainable cities through a comprehensive review of the relevant literature. The review focuses on several differing aspects of sustainable city formation. The paper provides insights on the interaction between the natural environment and human activities by identifying environmental effects resulting from this interaction; provides an introduction to the concept of sustainable urban development by underlining the important role of ecological planning in achieving sustainable cities; introduces the notion of urban ecosystems by establishing principles for the management of their sustainability; describes urban ecosystem sustainability assessment by introducing a review of current assessment methods, and; offers an outline of indexing urban environmental sustainability. The paper concludes with a summary of the findings.

Licensing system in Oman and literature review. Report to the Research Council of Oman, Muscat

This document reviews the existing literature in the area of novice driver behaviour and the impact of Graduated Driver Licencing (GDL) as a key response to young driver management. The document focuses on consolidating the available research evidence and identifying existing gaps in the current knowledge. The chapter reviews novice driver crash risk, the factors that influence novice driver behaviour, countermeasures used to address the problem, the learner phase, the provisional phase, The Australian example of GDL, compliance with the road laws and parental involvement in the GDL process...

Report : review of the literature : maintenance and rehabilitation costs for roads (Risk-based Analysis)

Realistic estimates of short- and long-term (strategic) budgets for maintenance and rehabilitation of road assessment management should consider the stochastic characteristics of asset conditions of the road networks so that the overall variability of road asset data conditions is taken into account. The probability theory has been used for assessing life-cycle costs for bridge infrastructures by Kong and Frangopol (2003), Zayed et.al. (2002), Kong and Frangopol (2003), Liu and Frangopol (2004), Noortwijk and Frangopol (2004), Novick (1993). Salem 2003 cited the importance of the collection and analysis of existing data on total costs for all life-cycle phases of existing infrastructure, including bridges, road etc., and the use of realistic methods for calculating the probable useful life of these infrastructures (Salem et. al. 2003). Zayed et. al. (2002) reported conflicting results in life-cycle cost analysis using deterministic and stochastic methods. Frangopol et. al. 2001 suggested that additional research was required to develop better life-cycle models and tools to quantify risks, and benefits associated with infrastructures. It is evident from the review of the literature that there is very limited information on the methodology that uses the stochastic characteristics of asset condition data for assessing budgets/costs for road maintenance and rehabilitation (Abaza 2002, Salem et. al. 2003, Zhao, et. al. 2004). Due to this limited information in the research literature, this report will describe and summarise the methodologies presented by each publication and also suggest a methodology for the current research project funded under the Cooperative Research Centre for Construction Innovation CRC CI project no 2003-029-C.

Literacy and identity : examining the metaphors in history and contemporary research

In this review, the authors interrogate the recent identity turn in literacy studies by asking the following: How do particular views of identity shape how researchers think about literacy and, conversely, how does the view of literacy taken by a researcher shape meanings made about identity? To address this question, the authors review various ways of conceptualizing identity by using five metaphors for identity documented in the identity literature: identity as (1) difference, (2) sense of self/subjectivity, (3) mind or consciousness, (4) narrative, and (5) position. Few literacy studies have acknowledged this range of perspectives on and views for conceptualizing identity and yet, subtle differences in identity theories have widely different implications for how one thinks about both how literacy matters to identity and how identity matters to literacy. The authors offer this review to encourage more theorizing of both literacy and identity as social practices and, most important, of how the two breathe life into each other.

Optimising learning in the workplace

There are three bodies of research that suggest ways in which learning in the workplace can be optimised. The first is evident in the emergent literature endorsing the need to include workplace pedagogies as useful epistemological tools for learners. It is now widely recognised that the workplace provides various pedagogies that facilitate and support learning.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

"I'm thinking 'bout moving in"... An examination of the issues impacting on the recruitment of secondary school graduates to the library and information profession

In recent years concern has been expressed internationally about the future of the library and information services (LIS) profession: recruitment and retention, changing skill sets and declining numbers of people choosing librarianship as a career are all factors contributing to an uncertain future. One area yet explored in any depth is the topic of why LIS studies are not perceived, let alone promoted, as a good first professional qualification for high school graduates. This paper considers the professional literature that examines the uptake of librarianship as a first qualification by school leavers and discusses, in the context of the Australian library sector, the role of professional associations, library schools, National and State Libraries, as well as individual libraries and librarians. Examples of best practice are presented to highlight the opportunities for inspiring and motivating students through well structured and stimulating work experience programs. The topic is relevant to all librarians who are interested in the future of the LIS profession. It is argued that the focus of the present conference on ‘moving up’ and ‘moving on’ can only have real significance when the profession has a more complete understanding of the barriers to and the opportunities for ‘moving in’.