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.

Consent for third molar tooth extractions in Australia and New Zealand: A review of current practice

Background Informed consent is the legal requirement to educate a patient about a proposed medical treatment or procedure so that he or she can make informed decisions. The purpose of the study was to examine the current practice for obtaining informed consent for third molar tooth extractions (wisdom teeth) by Oral and Maxillofacial Surgeons in Australia and New Zealand. Methods An online survey was sent to 180 consultant Oral and Maxillofacial Surgeons in Australia and New Zealand. Surgeons were asked to answer (yes/no) whether they routinely warned of a specific risk of third molar tooth extraction in their written consent. Results 71 replies were received (39%). The only risks that surgeons agreed should be routinely included in written consent were a general warning of infection (not alveolar osteitis), inferior alveolar nerve damage (temporary and permanent) and lingual nerve damage (temporary and permanent). Conclusions There is significant variability among Australian and New Zealand Oral and Maxillofacial Surgeons regarding risk disclosure for third molar tooth extractions. We aim to improve consistency in consent for third molar extractions by developing an evidence-based consent form.

The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis

Multiple sclerosis (MS) is an autoimmune disease with a genetic component, caused at least in part by aberrant lymphocyte activity. The whole blood mRNA transcriptome was measured for 99 untreated MS patients: 43 primary progressive MS, 20 secondary progressive MS, 36 relapsing remitting MS and 45 age-matched healthy controls. The ANZgene Multiple Sclerosis Genetics Consortium genotyped more than 300 000 SNPs for 115 of these samples. Transcription from genes on translational regulation, oxidative phosphorylation, immune synapse and antigen presentation pathways was markedly increased in all forms of MS. Expression of genes tagging T cells was also upregulated (P < 10-12) in MS. A T cell gene signature predicts disease state with a concordance index of 0.79 with age and gender as co-variables, but the signature is not associated with clinical course or disability. The ANZgene genome wide association screen identified two novel regions with genome wide significance: one encoding the T cell co-stimulatory molecule, CD40; the other a region on chromosome 12q13-14. The CD40 haplotype associated with increased MS susceptibility has decreased gene expression in MS (P < 0.0007). The second MS susceptibility region includes 17 genes on 12q13-14 in tight linkage disequilibrium. Of these, only 13 are expressed in leukocytes, and of these the expression of one, FAM119B, is much lower in the susceptibility haplotype (P tdthomlt; 10-14). Overall, these data indicate dysregulation of T cells can be detected in the whole blood of untreated MS patients, and supports targeting of activated T cells in therapy for all forms of MS.

A case study of teaching English and multimodality with ICTs: Constraints and possibilities

Current Australian policies and curricular frameworks demand that teachers and students use technology creatively and meaningfully in classrooms to develop students into 21C technological citizens. English teachers and students also have to learn new metalanguage around visual grammar since multimodal tasks often combine creative with critical General Capabilities (GC) with that of the of ICTs and literacy in the Australian Curriculum: English (AC:E). Both teachers and learners come to these tasks with varying degrees of techno-literacy, skills and access to technologies. This paper reports on case-study research following a technology based collaborative professional development (PD) program between a university Lecturer facilitator and English Teachers in a secondary Catholic school. The study found that the possibilities for creative and critical engagement are rich, but there are real grounded constraints such as lack of time, impeding teachers’ ability to master and teach new technologies in classrooms. Furthermore, pedagogical approaches are affected by technical skill levels and school infrastructure concerns which can militate against effective use of ICTs in school settings. The research project was funded by the Brisbane Catholic Education Office and focused on how teachers can be supported in these endeavours in educational contexts as they prepare students of English to be creative global citizens who use technology creatively.

Sequence specific interaction of Mycobacterium smegmatis topoisomerase I with duplex DNA

We have identified strong topoisomerase sites (STS) for Mycobacteruim smegmatis topoisomerase I in double-stranded DNA context using electrophoretic mobility shift assay of enzyme-DNA covalent complexes; Mg2+, an essential component for DNA relaxation activity of the enzyme, is not required for binding to DNA, The enzyme makes single-stranded nicks, with transient covalent interaction at the 5'-end of the broken DNA strand, a characteristic akin to prokaryotic topoisomerases. More importantly, the enzyme binds to duplex DNA having a preferred site with high affinity, a. property similar to the eukaryotic type I topoisomerases, The preferred cleavage site is mapped on a 65 bp duplex DNA and found to be CG/TCTT. Thus, the enzyme resembles other prokaryotic type I topoisomerases in mechanistics of the reaction, but is similar to eukaryotic enzymes in DNA recognition properties.

Studies of the specific gravity of some Indian coal ashes

One of the major problems faced by coal based thermal power stations is handling and disposal of ash. Among the various uses of fly ash, the major quantity of ash produced is used in geotechnical engineering applications such as construction of embankments, as a backfill material, etc. The generally low specific gravity of fly ash resulting in low unit weight as compared to soils is an attractive property for its use in geotechnical applications. In general, specific gravity of coal ash lies around 2.0 but can vary to a large extent (1.6 to 3.1). The variation of specific gravity of coal ash is due to the combination of various factors like gradation, particle shape, and chemical composition. Since specific gravity is an important physical property, it has been studied in depth for three Indian coal ashes and reported in this paper.

Saussure, science and structuralism

This paper investigates the influence of an extensive family tradition in science-based interdisciplinary research on the origins and development of Ferdinand de Saussure's 'structuralism', or his 'scientization' of linguistic study.

IFN-gamma inhibits growth of WISH cells in a cell cycle phase-specific manner

Treatment of WISH (human amnion) cells with interferon-gamma (IFN-gamma) inhibits their growth. Release of the cells from IFN-gamma-mediated growth inhibition led to a rapid and significant increase in DNA synthesis, followed by doubling of cell numbers. The DNA synthesis profile was strikingly similar to that shown by WISH cells released from growth arrest by the G(1)/S phase inhibitor, aphidicolin, This strongly suggested that IFN-gamma treatment leads to growth inhibition of WISH cells at the G(1)/S boundary of the cell cycle. In contrast, IFN-alpha blocked growth of these cells at the G(0)/G(1) boundary.

Molecular theory for the effects of specific solute-solvent interaction on the diffusion of a solute particle in a molecular liquid

An understanding of the effect of specific solute-solvent interactions on the diffusion of a solute probe is a long standing problem of physical chemistry. In this paper a microscopic treatment of this effect is presented. The theory takes into account the modification of the solvent structure around the solute due to this specific interaction between them. It is found that for strong, attractive interaction, there is an enhanced coupling between the solute and the solvent dynamic modes (in particular, the density mode), which leads to a significant increase in the friction on the solute. The diffusion coefficient of the solute is found to depend strongly and nonlinearly on the magnitude of the attractive interaction. An interesting observation is that specific solute-solvent interaction can induce a crossover from a sliplike to a sticklike diffusion. In the limit of strong attractive interaction, we recover a dynamic version of the solvent-berg picture. On the other hand, for repulsive interaction, the diffusion coefficient of the solute increases. These results are in qualitative agreement with recent experimental observations.

Corporate governance and law reform in Japan: From the lost decade to the end of history?

Japan is in the midst of massive law reform. Mired in ongoing recession since the early 1990s, Japan has been implementing a new regulatory blueprint to kickstart a sluggish economy through structural change. A key element to this reform process is a rethink of corporate governance and its stakeholder relations. With a patchwork of legislative initiatives in areas as diverse as corporate law, finance, labour relations, consumer protection, public administration and civil justice, this new model is beginning to take shape. But to what extent does this model represent a break from the past? Some commentators are breathlessly predicting the "Americanisation" of Japanese law. They see the triumph of Western-style capitalism - the "End of History", to borrow the words of Francis Fukuyama - with its emphasis on market-based, arms-length transactions. Others are more cautious, advancing the view that there new reforms are merely "creative twists" on what is a uniquely (although slowly evolving) strand of Japanese capitalism. This paper takes issue with both interpretations. It argues that the new reforms merely follow Japan's long tradition of 'adopting and adapting' foreign models to suit domestic purposes. They are neither the wholesale importation of "Anglo-Saxon" regulatory principles nor a thin veneer over a 'uniquely unique' form of Confucian cultural capitalism. Rather, they represent a specific and largely political solution (conservative reformism) to a current economic problem (recession). The larger themes of this paper are 'change' and 'continuity'. 'Change' suggests evolution to something identifiable; 'continuity' suggests adhering to an existing state of affairs. Although notionally opposites, 'change' and 'continuity' have something in common - they both suggest some form of predictability and coherence in regulatory reform. Our paper, by contrast, submits that Japanese corporate governance reform or, indeed, law reform more generally in Japan, is context-specific, multi-layered (with different dimensions not necessarily pulling all in the same direction for example, in relations with key outside suppliers), and therefore more random or 'chaotic'.

Themes in landscape architecture publishing: Past trends, future needs

Many scholars acknowledge the need for rigorous research in landscape architecture to improve practice and teaching, and several recent studies have explored research trends in the discipline. This study continues this exploration by reviewing the articles published in the three prominent English- language landscape architecture journals: Landscape Journal, Landscape Review, and the Journal of Landscape Architecture. Specifically, this study analyzes the abstracts from 441 research articles to determine specific themes and publishing trends over 31 years (1982–2013). Findings indicate that “history” is by far the most prominent research theme, followed by “social and cultural processes and issues” and “aesthetics.” Several themes—such as “sustainability and green infrastructure,” “participation and collaboration,” and “research methods and methodologies”—have become more prominent in recent years. However, topics of current social and political concern—such as “climate change,” “active living,” “energy,” and “health”—are not yet prominent themes in the research literature, and could be key areas for future contribution. With the exception of a few themes, findings also suggest a moderate degree of alignment between research and practice. The article concludes with recommendations for future areas of research that will better position landscape architecture as a research- oriented profession with broad social relevance.

Specific rolling circle amplification of low-copy human polyomaviruses BKV, HPyV6, HPyV7, TSPyV, and STLPyV

Eleven new human polyomaviruses have been recently discovered, yet for most of these viruses, little is known of their biology and clinical impact. Rolling circle amplification (RCA) is an ideal method for the amplification of the circular polyomavirus genome due to its high fidelity amplification of circular DNA. In this study, a modified RCA method was developed to selectively amplify a range of polyomavirus genomes. Initial evaluation showed a multiplexed temperature-graded reaction profile gave the best yield and sensitivity in amplifying BK polyomavirus in a background of human DNA, with up to 1 × 10(8)-fold increases in viral genomes from as little as 10 genome copies per reaction. Furthermore, the method proved to be more sensitive and provided a 200-fold greater yield than that of random hexamers based standard RCA. Application of the method to other novel human polyomaviruses showed successful amplification of TSPyV, HPyV6, HPyV7, and STLPyV from low-viral load positive clinical samples, with viral genome enrichment ranging from 1 × 10(8) up to 1 × 10(10). This directed RCA method can be applied to selectively amplify other low-copy polyomaviral genomes from a background of competing non-specific DNA, and is a useful tool in further research into the rapidly expanding Polyomaviridae family.

Cloning and development of pathotype-specific SCAR marker associated with Sclerospora graminicola isolates from pearl millet

Downy mildew pathogen of pearl millet in India is associated with the spread of the highly virulent Sclerospora graminicola pathotype-1. Twenty-seven S. graminicola isolates were screened using 20 intersimple sequence repeats (ISSR). Dinucleotide repeat primer [17898A-(CA)(6) AC] amplified a similar to 600 bp fragment specific to five isolates of pathotype-1 (Sg 048, Sg 153, Sg 212, DM-11 and DM-90). The ISSR fragment linked with pathotype-1 was cloned successfully and sequenced. To convert ISSR fragments into pathotype-specific sequence characterised amplified region (SCAR) markers, PCR primers were designed using a sequence of the cloned DNA fragment. PCR amplification using SCAR primer pair (UOM3-Sg-Path1-F/R) amplified a single 284 bp band only in isolates of S. graminicola pathotype-1. This SCAR primer pair did not amplify the 284 bp product from the other five S. graminicola pathotypes or a negative control, which demonstrates primer specificity for pathotype-1. The SCAR primer pair (UOM3-Sg-Path1-F/R) obtained in this study will provide a valuable tool for rapid identification and specific detection of S. graminicola pathotype-1.

Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model

The aim of this study is to investigate the blood flow pattern in carotid bifurcation with a high degree of luminal stenosis, combining in vivo magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed two-equation transitional model was employed to evaluate wall shear stress (WSS) distribution and pressure drop across the stenosis, which are closely related to plaque vulnerability. A patient with an 80% left carotid stenosis was imaged using high resolution MRI, from which a patient-specific geometry was reconstructed and flow boundary conditions were acquired for CFD simulation. A transitional model was implemented to investigate the flow velocity and WSS distribution in the patient-specific model. The peak time-averaged WSS value of approximately 73Pa was predicted by the transitional flow model, and the regions of high WSS occurred at the throat of the stenosis. High oscillatory shear index values up to 0.50 were present in a helical flow pattern from the outer wall of the internal carotid artery immediately after the throat. This study shows the potential suitability of a transitional turbulent flow model in capturing the flow phenomena in severely stenosed carotid arteries using patient-specific MRI data and provides the basis for further investigation of the links between haemodynamic variables and plaque vulnerability. It may be useful in the future for risk assessment of patients with carotid disease.

Normalized wall index specific and MRI-based stress analysis of atherosclerotic carotid plaques: A study comparing acutely symptomatic and asymptomatic patients

Background: Biomechanical stresses play an important role in determining plaque stability. Quantification of these simulated stresses can be potentially used to assess plaque vulnerability and differentiate different patient groups. Methods and Results: 54 asymptomatic and 45 acutely symptomatic patients underwent in vivo multicontrast magnetic resonance imaging (MRI) of the carotid arteries. Plaque geometry used for finite element analysis was derived from in vivo MRI at the sites of maximum and minimum plaque burden. In total, 198 slices were used for the computational simulations. A pre-shrink technique was used to refine the simulation. Maximum principle stress at the vulnerable plaque sites (ie, critical stress) was extracted for the selected slices and a comparison was performed between the 2 groups. Critical stress in the slice with maximum plaque burden is significantly higher in acutely symptomatic patients as compared to asymptomatic patients (median, inter quartile range: 198.0 kPa (119.8-359.0 kPa) vs 138.4 kPa (83.8-242.6 kPa), P=0.04). No significant difference was found in the slice with minimum plaque burden between the 2 groups (196.7 kPa (133.3-282.7 kPa) vs 182.4 kPa (117.2-310.6 kPa), P=0.82). Conclusions: Acutely symptomatic carotid plaques have significantly high biomechanical stresses than asymptomatic plaques. This might be potentially useful for establishing a biomechanical risk stratification criteria based on plaque burden in future studies.