Two-Photon Fluorescence Microscopy Imaging of Cellular Oxidative Stress Using Profluorescent Nitroxides

A range of varying chromophore nitroxide free radicals and their nonradical methoxyamine analogues were synthesized and their linear photophysical properties examined. The presence of the proximate free radical masks the chromophore’s usual fluorescence emission, and these species are described as profluorescent. Two nitroxides incorporating anthracene and fluorescein chromophores (compounds 7 and 19, respectively) exhibited two-photon absorption (2PA) cross sections of approximately 400 G.M. when excited at wavelengths greater than 800 nm. Both of these profluorescent nitroxides demonstrated low cytotoxicity toward Chinese hamster ovary (CHO) cells. Imaging colocalization experiments with the commercially available CellROX Deep Red oxidative stress monitor demonstrated good cellular uptake of the nitroxide probes. Sensitivity of the nitroxide probes to H2O2-induced damage was also demonstrated by both one- and two-photon fluorescence microscopy. These profluorescent nitroxide probes are potentially powerful tools for imaging oxidative stress in biological systems, and they essentially “light up” in the presence of certain species generated from oxidative stress. The high ratio of the fluorescence quantum yield between the profluorescent nitroxide species and their nonradical adducts provides the sensitivity required for measuring a range of cellular redox environments. Furthermore, their reasonable 2PA cross sections provide for the option of using two-photon fluorescence microscopy, which circumvents commonly encountered disadvantages associated with one-photon imaging such as photobleaching and poor tissue penetration.

Living with strangers: Urban space and the ethics of civility

Urban regeneration is occuring in cities across the world, as cities increase in scale and complexity. This chapter argues that in planning public spaces, greater consideration should be paid to sociability through consideration of the affective dimension of urban life.

Career path of a corruption entrepreneur

The study of criminal career paths is necessary to understand the methods of success employed by high-performing criminals. The aim of this article is to focus on the career path of Jack Herbert who set up and maintained extensive corruption networks between organised crime groups and police in the Australian state of Queensland. This study builds on Morselli’s work on the career paths of Sammy Gravano and Howard Marks that demonstrate how understanding social networks is an essential part of comprehending how organised criminals succeed. The data for this study were taken from the transcripts of the Fitzgerald Commission of Inquiry, which uncovered the extensive and resilient corruption network operated by Herbert. Herbert’s relationships have been plotted to establish the nature of his operations. The findings indicate that communication of trust both allows for success and sets the boundaries of a network. Most importantly, this case study identifies Herbert’s reliance on holding a monopoly as the cornerstone of his network power and position. This article adds to the literature on criminal career paths by moving away from a classic organised criminal grouping into the area of police corruption and uncovers the distinctive opportunities that this position offers the career criminal.

The duplicitous nature of inflammation in wound repair

Skin plays a key role in protecting the body from the onslaught of pathogens and toxins we meet during our lifetime; thus, out of necessity, we have developed a rapid repair mechanism that quickly plugs any holes in this vital organ. Upon injury, a series of highly coordinated overlapping events, that include inflammatory, proliferation and maturation phases, result in the hasty closure of the wound and restoration of skin integrity. Over the past decade it has become clear that a number of immune cells that regulate the inflammatory phase, whilst important for removal of invading pathogens, are not necessary for repair and in fact may be responsible for the subsequent scar formation that seems to have resulted from having such a rapid repair process. The magnitude and length of inflammation in the wound not only appears to dictate the extent of scar formation but also in some cases may even prevent wound closure. In this review we will explore the two sides of inflammation in wound healing and review current and future drug therapies that target inflammation to modulate the healing outcome.

Regulating the cost of small loans : overdue or overkill?

Small-amount short-term lending began in 1994 in response to the initial exemption of such loans from consumer credit regulation. Growing demand for such loans now produces industry turnover of approximately $800 million each year. Regulators recognised early the need for consumer protection due to the vulnerability of borrowers and the emergence of various predatory practices. This led to reforms designed to regulate these loans, prevent particular misconduct and provide remedies against injustice. Some were enacted as part of the National Consumer Credit Protection Act 2009 (Cth), which also imposed licensing and responsible lending requirements on lenders and increased consumer access to remedies. The Government has now introduced the Consumer Credit and Corporations Amendment (Enhancements) Bill 2011 which limits the price that can be charged for credit and restricts access to small loans. This article examines the extensive reforms which have taken place in this sector, and compares these regulatory approaches with the “bright line approach” of the Enhancements Bill. The article argues that the repercussions of this step will require careful monitoring to ensure that further harm is not suffered by those least able to bear it, and that the government will also need to facilitate other, more sustainable, solutions to the problem that small loans are currently used to solve. After we wrote this article, the Report of the Parliamentary Joint Committee on Corporations and Financial Services and the Report of the Senate Economics Legislation Committee on the Enhancements Bill were released. These are referred to in a postscript.

Multi-method, multi-theoretical, multi-level research in the learning sciences

We examine methodologies and methods that apply to multi-level research in the learning sciences. In so doing we describe how multiple theoretical frameworks informs the use of different methods that apply to social levels involving space-time relationships that are not accessible consciously as social life is enacted. Most of the methods involve analyses of video and audio files. Within a framework of interpretive research we present a methodology of event-oriented social science, which employs video ethnography, narrative, conversation analysis, prosody analysis, and facial expression analysis. We illustrate multi-method research in an examination of the role of emotions in teaching and learning. Conversation and prosody analyses augment facial expression analysis and ethnography. We conclude with an exploration of ways in which multi-level studies can be complemented with neural level analyses.

Numerical investigation of mechanical properties of nanowires : a review

Nanowires (NWs) have attracted intensive researches owing to the broad applications that arise from their remarkable properties. Over the last decade, immense numerical studies have been conducted for the numerical investigation of mechanical properties of NWs. Among these numerical simulations, the molecular dynamics (MD) plays a key role. Herein we present a brief review on the current state of the MD investigation of nanowires. Emphasis will be placed on the FCC metal NWs, especially the Cu NWs. MD investigations of perfect NWs’ mechanical properties under different deformation conditions including tension, compression, torsion and bending are firstly revisited. Following in succession, the studies for defected NWs including the defects of twin boundaries (TBs) and pre-existing defects are discussed. The different deformation mechanism incurred by the presentation of defects is explored and discussed. This review reveals that the numerical simulation is an important tool to investigate the properties of NWs. However, the substantial gaps between the experimental measurements and MD results suggest the urgent need of multi-scale simulation technique.

Evolutionary design of bone scaffolds with reference to material selection

The favourable scaffold for bone tissue engineering should have desired characteristic features, such as adequate mechanical strength and three-dimensional open porosity, which guarantee a suitable environment for tissue regeneration. In fact, the design of such complex structures like bone scaffolds is a challenge for investigators. One of the aims is to achieve the best possible mechanical strength-degradation rate ratio. In this paper we attempt to use numerical modelling to evaluate material properties for designing bone tissue engineering scaffold fabricated via the fused deposition modelling technique. For our studies the standard genetic algorithm was used, which is an efficient method of discrete optimization. For the fused deposition modelling scaffold, each individual strut is scrutinized for its role in the architecture and structural support it provides for the scaffold, and its contribution to the overall scaffold was studied. The goal of the study was to create a numerical tool that could help to acquire the desired behaviour of tissue engineered scaffolds and our results showed that this could be achieved efficiently by using different materials for individual struts. To represent a great number of ways in which scaffold mechanical function loss could proceed, the exemplary set of different desirable scaffold stiffness loss function was chosen. © 2012 John Wiley & Sons, Ltd.

Clinical performance of a new silicone hydrogel contact lens over 6 months of extended wear

Purpose: Silicone hydrogel contact lenses (CLs) are becoming increasingly popular for daily wear (DW), extended wear (EW) and continuous wear (CW), due to their higher oxygen transmissibility compared to hydrogel CLs. The aim of this study was to investigate the clinical and subjective performance of asmofilcon A (Menicon Co., Ltd), a new surface treated silicone hydrogel CL, during 6-night EW over 6 months (M). Methods: A prospective, randomised, single-masked, monadic study was conducted. N=60 experienced DW soft CL wearers were randomly assigned to wear either asmofilcon A (test: Dk=129, water content (WC)=40%, Nanogloss surface treatment) or senofilcon A (control: Dk=103, WC=38%, PVP internal wetting agent, Vistakon, Johnson & Johnson Vision Care) CLs bilaterally for 6 M on an EW basis. A PHMB-preserved solution (Menicon Co., Ltd) was dispensed for CL care. Evaluations were conducted at CL delivery and after 1 week (W), 4 W, 3 M and 6 M of EW. At each visit, a range of objective and subjective clinical performance measures were assessed. Results: N=50 subjects (83%) successfully completed the study, with the majority of discontinuations due to loss to follow-up (n=3) or moving away/travel (n=5). N=2 subjects experienced adverse events; n=1 unilateral red eye with asmofilcon A and n=1 asymptomatic infiltrate with senofilcon A. There were no significant differences in high or low contrast distance visual acuity (HCDVA or LCDVA) between asmofilcon A and senofilcon A; however, LCDVA decreased significantly over time with both CL types (p<0.05). The two CL types did not vary significantly with respect to any of the objective and subjective measures assessed (p>0.05); CL fitting characteristics and CL surface measurements were very similar and mean bulbar and limbal redness measures were always less than grade 1.0. Superior palpebral conjunctival injection showed a statistically, but not clinically, significant increase over time with both CL types (p<0.05). Corneal staining did not vary significantly between asmofilcon A and senofilcon A (p>0.05), with low median gradings of less than 0.5 observed for all areas assessed. There were no solution-related staining reactions observed with either CL type. The asmofilcon A and senofilcon A CLs were both rated highly with respect to overall comfort, with medians of 14 or 15 hours of comfortable lens wearing time per day reported at each of the study visits (p>0.05). Conclusions: Over 6 months of EW, the asmofilcon A and senofilcon A CLs performed in a similar manner with respect to visual acuity, ocular health and CL performance measures. Some changes over time were observed with both CL types, including reduced LCDVA and increased superior palpebral injection, which warrant further investigation in longer-term EW studies. Asmofilcon A appeared to be equivalent in performance to senofilcon A.

Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript

Abstract Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P = 3.9 × 10−22). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P = 1.9 × 10−34). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk.

An action research approach for the professional development of Vietnamese nurse educators

Nurse education in Viet Nam is undergoing substantial reform. In order to facilitate the change, in 2007 the Viet Nam Nurses Association formed a collaborative partnership with the School of Nursing and Midwifery at an Australia university. This collaboration gave rise to the Viet Nam Nursing Capacity Building Project under the leadership of Professor Genevieve Gray, funded by the Atlantic Philanthropies. The new four year competency based nursing curriculum frame is expected to be implemented in September 2011 following approval by the Viet Nam Ministry of Education. The focus of this paper is the Teaching Fellowships Program, an initiative of the Viet Nam Nursing Capacity Building Project, developed to help meet the challenges associated with leading and dealing with the curriculum change. The paper explores the development of the program and justifies an action research approach, illuminates key issues, and briefly refers to changes to the next fellowship program.