Inhibition of myeloperoxidase- and neutrophil-mediated oxidant production by tetraethyl and tetramethyl nitroxides

The powerful oxidant HOCl (hypochlorous acid and its corresponding anion, −OCl) generated by the myeloperoxidase (MPO)–H2O2–Cl− system of activated leukocytes is strongly associated with multiple human inflammatory diseases; consequently there is considerable interest in inhibition of this enzyme. Nitroxides are established antioxidants of low toxicity that can attenuate oxidation in animal models, with this ascribed to superoxide dismutase or radical-scavenging activities. We have shown (M.D. Rees et al., Biochem. J. 421, 79–86, 2009) that nitroxides, including 4-amino-TEMPO (4-amino-2,2,6,6-tetramethylpiperidin-1-yloxyl radical), are potent inhibitors of HOCl formation by isolated MPO and activated neutrophils, with IC50 values of ~1 and ~6 µM respectively. The utility of tetramethyl-substituted nitroxides is, however, limited by their rapid reduction by biological reductants. The corresponding tetraethyl-substituted nitroxides have, however, been reported to be less susceptible to reduction. In this study we show that the tetraethyl species were reduced less rapidly than the tetramethyl species by both human plasma (89–99% decreased rate of reduction) and activated human neutrophils (62–75% decreased rate). The tetraethyl-substituted nitroxides retained their ability to inhibit HOCl production by MPO and activated neutrophils with IC50 values in the low-micromolar range; in some cases inhibition was enhanced compared to tetramethyl substitution. Nitroxides with rigid structures (fused oxaspiro rings) were, however, inactive. Overall, these data indicate that tetraethyl-substituted nitroxides are potent inhibitors of oxidant formation by MPO, with longer plasma and cellular half-lives compared to the tetramethyl species, potentially allowing lower doses to be employed.

Theorising the impacts of digitally mediated social interaction on diasporic identity formation: A case of Chinese diaspora in Australia

With the scope of Chinese diaspora in Australia, this paper theorises the impacts of digitally mediated social interaction on diasporic identity formation in the new media landscape. People’s identity is the outcome of their social interactions with other individuals. In the new media landscape, digital media technologies are changing the way in which people communicate with others. On one hand, space and time are unprecedentedly compressed by media technologies so people can maintain more frequent and instant connections with others than before. On the other hand, the digital media technologies have constructed a virtual social space that might withdraw people from their physical social interactions. As we witness today, our social interactions are increasing digitally mediated, in the forms of posts and comments in social network sites, as well as the messages in social apps. As to the diasporic groups, this new media landscape is presenting a challenge to their identity formation. They physically live in the host countries but still keep close social and cultural connections with their homelands. Facilitated by digital media technologies, they are facing two platforms in which they can practice different identity performances: one is the digitally mediated social network; the other is the physical social network. In the case of Chinese diaspora, the situation is more complex due to the language factor and media censorship in Mainland China, which will be articulated in the main text. This paper aims to fill a gap between media studies and diaspora research. Most of existing research on the relationship between diasporic identity and media primarily focuses on the development of ethnic media institutions, and the production and consumption of ethnic media in the pre-digital media context. However, the process of globalisation and digital media technologies are increasing the homogeneity and hybridity of media content worldwide. In this new context, attributing the formation of different identities to the consumption of media content is arguable to some extent. Therefore, the overlapped area of new media studies and diaspora research still has space deserves further investigation.

Osteoclast formation from circulating precursors in osteoporosis

Objective: An imbalance between bone formation and bone resorption is thought to underlie the pathogenesis of reduced bone mass in osteoporosis. Bone resorption is carried out by osteoclasts, which are formed from marrow-derived cells that circulate in the monocyte fraction. Ihe aim of this study was to determine the role of osteoclast formation in the pathogenesis of bone loss in osteoporosis. Methods: The proportion of circulating osteoclast precursors and their relative sensitivity to the osteoclastogenic effects of M-CSF, 1,25(OH)2D3 and RANKL were assessed in primary osteoporosis patients and normal controls. Results: Although there was no difference in the number of circulating osteoclast precursors in osteoporosis patients and normal controls, osteoclasts formed from osteoporosis patients exhibited substantially increased resorptive activity relative to normal controls. Although no increased sensitivity to the osteoclastogenic effects of 1,25(OH)2D3 or M-CSF was noted, increased bone resorption was found in osteoporosis peripheral blood mononuclear cell (PBMC) cultures to which these factors were added. Conclusion: Our findings suggest that osteoclast functional activity rather than formation is increased in primary involutional osteoporosis and that dexamethasone acts to increase osteoclast formation.

State-formation, teaching techniques, and globalization as aporia

Eleanor Smith [pseudonym], teacher : I was talking to the kids about MacDonalds*/I forget exactly what the context was*/I said ‘‘ah, the Americans call them French fries, and, you know, MacDonalds is an American chain and they call them French fries because the Americans call them French fries’’, and this little Australian kid in the front row, very Australian child, said to me, ‘‘I call them French fries!’’ . . . Um, a fourth grade boy whom I taught in 1993 at this school, the world basketball championships were on . . . Americans were playing their dream machine and the Boomers were up against them . . . and, ah, this boy was very interested in basketball . . . but it’s not in my blood, not in the way cricket is for example . . . Um, Um, and I said to this fellow, ‘‘um, well’’, I said, ‘‘Australia’s up against Dream Machine tomorrow’’. He [Jason, pseudonym] said, ‘‘Ah, you know, Boomers probably won’t win’’. . . . I said, ‘‘Well that’s sport, mate’’. I said, ‘‘You never know in sport. Australia might win’’. And he looked at me and he said, ‘‘I’m not going for Australia, I’m going for America’’. This is from an Australian boy! And I thought so strong is the hype, so strong is the, is the, power of the media, etc., that this boy is not [pause], I can’t tell you how outraged I was. Here’s me as an Australian and I don’t even support basketball, it’s not even my sport, um, but that he would respond like that because of the power of the American machine that’s converting kids’ minds, the way they think, where they’re putting their loyalties, etc. I was just appalled, but that’s where he was. And when I asked kids for their favourite place, he said Los Angeles.

Comparative proteomics of uropathogenic Escherichia coli during growth in human urine identify UCA-like (UCL) fimbriae as an adherence factor involved in biofilm formation and binding to uroepithelial cells

Uropathogenic Escherichia coli (UPEC) are the primary cause of urinary tract infection (UTI) in humans. For the successful colonisation of the human urinary tract, UPEC employ a diverse collection of secreted or surface-exposed virulence factors including toxins, iron acquisition systems and adhesins. In this study, a comparative proteomic approach was utilised to define the UPEC pan and core surface proteome following growth in pooled human urine. Identified proteins were investigated for subcellular origin, prevalence and homology to characterised virulence factors. Fourteen core surface proteins were identified, as well as eleven iron uptake receptor proteins and four distinct fimbrial types, including type 1, P, F1C/S and a previously uncharacterised fimbrial type, designated UCA-like (UCL) fimbriae in this study. These pathogenicity island (PAI)-associated fimbriae are related to UCA fimbriae of Proteus mirabilis, associated with UPEC and exclusively found in members of the E. coli B2 and D phylogroup. We further demonstrated that UCL fimbriae promote significant biofilm formation on abiotic surfaces and mediate specific attachment to exfoliated human uroepithelial cells. Combined, this study has defined the surface proteomic profiles and core surface proteome of UPEC during growth in human urine and identified a new type of fimbriae that may contribute to UTI.

Rapid, selective, and reversible Nitroxide Radical Coupling (NRC) reactions at amibient temperature

High activation of polystyrene with bromine end groups (PSTY-Br) to their incipient radicals occurred in the presence of Cu(I)Br, Me6TREN, and DMSO solvent. These radicals were then trapped by nitroxide species leading to coupling reactions between PSTY-Br and nitroxides that were ultrafast and selective in the presence of a diverse range of functional groups. The nitroxide radical coupling (NRC) reactions have the attributes of a “click” reaction with near quantitative yields of product formed, but through the reversibility of this reaction, it has the added advantage of permitting the exchange of chemical functionality on macromolecules. Conditions were chosen to facilitate the disproportionation of Cu(I)Br to the highly activating nascent Cu(0) and deactivating Cu(II)Br2 in the presence of DMSO solvent and Me6TREN ligand. NRC at room temperature gave near quantitative yields of macromolecular coupling of low molecular weight polystyrene with bromine chain-ends (PSTY-Br) and nitroxides in under 7 min even in the presence of functional groups (e.g., −≡, −OH, −COOH, −NH2, =O). Utilization of the reversibility of the NRC reaction at elevated temperatures allowed the exchange of chain-end groups with a variety of functional nitroxide derivatives. The robustness and orthogonality of this NRC reaction were further demonstrated using the Cu-catalyzed azide/alkyne “click” (CuAAC) reactions, in which yields greater than 95% were observed for coupling between PSTY-N3 and a PSTY chain first trapped with an alkyne functional TEMPO (PSTY-TEMPO-≡).

Depositional model for the early Miocene turbidite sequence, the Whakataki Formation, NZ

This research examined the influence of tectonic activity on submarine sedimentation processes, through a deposit-based analysis of turbidites in outcrop. A comprehensive field study of the Miocene Whakataki Formation yielded significant data that was analysed using methods of process-sedimentology, stratigraphy, and ichnology. Signatures of the tectonically active depositional environment were identifiable at very high resolution, from grain composition and texture to trace-fossil assemblages, as well as on a broader-scale in stratigraphic stacking patterns and structural deformation. From these results and environmental interpretations, an original facies characterisation and conceptual depositional model have been established.

Radical nursing and the emergence of technique as healthcare technology

The integration of technology in care is core business in nursing and this role requires that we must understand and use technology informed by evidence that goes much deeper and broader than actions and behaviours. We need to delve more deeply into its complexity because there is nothing minor or insignificant about technology as a major influence in healthcare outcomes and experiences. Evidence is needed that addresses technology and nursing from perspectives that examine the effects of technology, especially related to increasing demands for efficiency, the relationship of technology to nursing and caring, and a range of philosophical questions associated with empowering people in their healthcare choices. Specifically, there is a need to confront in practice the ways technique influences care. Technique is the creation of a kind of thinking that is necessary for contemporary healthcare technology to develop and be applied in an efficient and rational manner. Technique is not an entity or specific thing, but rather a way of thinking that seeks to shape and organize nursing activity, and manage efficiently individual difference(s) in care. It emphasizes predetermined causal relationships, conformity, and sameness of product, process, and thought. In response is needed a radical vision of nursing that attempts in a real sense to ensure we meet the needs of individuals and their community. Activism and advocacy are needed, and a willingness to create a certain detachment from the imperatives that technique demands. It is argued that our responsibility as nurses is to respond in practice to the errors, advantages, difficulties, and temptations of technology for the benefit of those who most need our assistance and care.

Atmospheric visibility and PM10 as indicators of new particle formation in an urban environment

It is well-known that new particle formation (NPF) in the atmosphere is inhibited by pre-existing particles in the air that act as condensation sinks to decrease the concentration and, thus, the supersaturation of precursor gases. In this study, we investigate the effects of two parameters - atmospheric visibility, expressed as the particle back-scatter coefficient (BSP), and PM10 particulate mass concentration, on the occurrences of NPF events in an urban environment where the majority of precursor gases originate from motor vehicle and industrial sources. This is the first attempt to derive direct relationships between each of these two parameters and the occurrence of NPF. NPF events were identified from data obtained with a neutral cluster and air ion spectrometer over 245 days within a calendar year. Bayesian logistic regression was used to determine the probability of observing NPF as functions of BSP and PM10. We show that the BSP at 08 h on a given day is a reliable indicator of an NPF event later that day. The posterior median probability of observing an NPF event was greater than 0.5 (95%) when the BSP at 08 h was less than 6.8 Mm-1.

Direct electrochemical formation of nanostructured amorphous Co(OH)2 on gold electrodes with enhanced activity for the oxygen evolution reaction.

The oxides of cobalt have recently been shown to be highly effective electrocatalysts for the oxygen evolution reaction (OER) under alkaline conditions. In general species such as Co3O4 and CoOOH have been investigated that often require an elevated temperature step during their synthesis to create crystalline materials. In this work we investigate the rapid and direct electrochemical formation of amorphous nanostructured Co(OH)2 on gold electrodes under room temperture conditions which is a highly active precursor for the OER. During the OER some conversion to crystalline Co3O4 occurs at the surface, but the bulk of the material remains amorphous. It is found that the underlying gold electrode is crucial to the materials enhanced performance and provides higher current density than can be achieved using carbon, palladium or copper support electrodes. This catalyst exhibits excellent activity with a current density of 10 mA cm-2 at an overpotential of 360 mV with a high turnover frequency of 2.1 s-1 in 1 M NaOH. A Tafel slope of 56 mV dec-1 at low overpotentials and a slope of 122 mV dec-1 at high overpotentials is consistent with the dual barrier model for the electrocatalytic evolution of oxygen. Significantly, the catalyst maintains excellent activity for up to 24 hr of continuous operation and this approach offers a facile way to create a highly effective and stable material.

Efficient surface modification of biomaterial to prevent biofilm formation and the attachment of microorganisms

Biomaterials play a fundamental role in disease management and the improvement of health care. In recent years, there has been a significant growth in the diversity, function, and number of biomaterials used worldwide. Yet, attachment of pathogenic microorganisms onto biomaterial surfaces remains a significant challenge that substantially undermines their clinical applicability, limiting the advancement of these systems. The emergence and escalating pervasiveness of antibiotic-resistant bacterial strains makes the management of biomaterial-associated nosocomial infections increasingly difficult. The conventional post-operative treatment of implant-caused infections using systemic antibiotics is often marginally effective, further accelerating the extent of antimicrobial resistance. Methods by which the initial stages of bacterial attachment and biofilm formation can be restricted or prevented are therefore sought. The surface modification of biomaterials has the potential to alleviate pathogenic biofouling, therefore preventing the need for conventional antibiotics to be applied.

Fabrication and characterization of plasma polymer thin films from monoterpene alcohols for applications in organic electronics and biotechnology

After more than twenty years of basic and applied research, the use of nanotechnology in the design and manufacture of nanoscale materials is rapidly increasing, particularly in commercial applications that span from electronics across renewable energy areas, and biomedical devices. Novel polymers are attracting significant attention for they promise to provide a low−cost high−performance alternative to existing materials. Furthermore, these polymers have the potential to overcome limitations imposed by currently available materials thus enabling the development of new technologies and applications that are currently beyond our reach. This work focuses on the development of a range of new low−cost environmentally−friendly polymer materials for applications in areas of organic (flexible) electronics, optics, and biomaterials. The choice of the monomer reflects the environmentally−conscious focus of this project. Terpinen−4−ol is a major constituent of Australian grown Melaleuca alternifolia (tea tree) oil, attributed with the oil's antimicrobial and anti−inflammatory properties. Plasma polymerisation was chosen as a deposition technique for it requires minimal use of harmful chemicals and produces no hazardous by−products. Polymer thin films were fabricated under varied process conditions to attain materials with distinct physico−chemical, optoelectrical, biological and degradation characteristics. The resultant materials, named polyterpenol, were extensively characterised using a number of well−accepted and novel techniques, and their fundamental properties were defined. Polyterpenol films were demonstrated to be hydrocarbon rich, with variable content of oxygen moieties, primarily in the form of hydroxyl and carboxyl functionalities. The level of preservation of original monomer functionality was shown to be strongly dependent on the deposition energy, with higher applied power increasing the molecular fragmentation and substrate temperature. Polyterpenol water contact angle contact angle increased from 62.7° for the 10 W samples to 76.3° for the films deposited at 100 W. Polymers were determined to resist solubilisation by water, due to the extensive intermolecular and intramolecular hydrogen bonds present, and other solvents commonly employed in electronics and biomedical processing. Independent of deposition power, the surface topography of the polymers was shown to be smooth (Rq <0.5 nm), uniform and defect free. Hardness of polyterpenol coatings increased from 0.33 GPa for 10 W to 0.51 GPa for 100 W (at 500 μN load). Coatings deposited at higher input RF powers showed less mechanical deformation during nanoscratch testing, with no considerable damage, cracking or delamination observed. Independent of the substrate, the quality of film adhesion improved with RF power, suggesting these coatings are likely to be more stable and less susceptible to wear. Independent of fabrication conditions, polyterpenol thin films were optically transparent, with refractive index approximating that of glass. Refractive index increased slightly with deposition power, from 1.54 (10 W) to 1.56 (100 W) at 500 nm. The optical band gap values declined with increasing power, from 2.95 eV to 2.64 eV, placing the material within the range for semiconductors. Introduction of iodine impurity reduced the band gap of polyterpenol, from 2.8 eV to 1.64 eV, by extending the density of states more into the visible region of the electromagnetic spectrum. Doping decreased the transparency and increased the refractive index from 1.54 to 1.70 (at 500 nm). At optical frequencies, the real part of permittivity (k) was determined to be between 2.34 and 2.65, indicating a potential low-k material. These permittivity values were confirmed at microwave frequencies, where permittivity increased with input RF energy – from 2.32 to 2.53 (at 10 GHz ) and from 2.65 to 2.83 (at 20 GHz). At low frequencies, the dielectric constant was determined from current−voltage characteristics of Al−polyterpenol−Al devices. At frequencies below 100 kHz, the dielectric constant varied with RF power, from 3.86 to 4.42 at 1 kHz. For all samples, the resistivity was in order of 10⁸−10⁹ _m (at 6 V), confirming the insulating nature of polyterpenol material. In situ iodine doping was demonstrated to increase the conductivity of polyterpenol, from 5.05 × 10⁻⁸ S/cm to 1.20 × 10⁻⁶ S/cm (at 20 V). Exposed to ambient conditions over extended period of time, polyterpenol thin films were demonstrated to be optically, physically and chemically stable. The bulk of ageing occurred within first 150 h after deposition and was attributed to oxidation and volumetric relaxation. Thermal ageing studies indicated thermal stability increased for the films manufactured at higher RF powers, with degradation onset temperature associated with weight loss shifting from 150 ºC to 205 ºC for 10 W and 100 W polyterpenol, respectively. Annealing the films to 405 °C resulted in full dissociation of the polymer, with minimal residue. Given the outcomes of the fundamental characterisation, a number of potential applications for polyterpenol have been identified. Flexibility, tunable permittivity and loss tangent properties of polyterpenol suggest the material can be used as an insulating layer in plastic electronics. Implementation of polyterpenol as a surface modification of the gate insulator in pentacene-based Field Effect Transistor resulted in significant improvements, shifting the threshold voltage from + 20 V to –3 V, enhancing the effective mobility from 0.012 to 0.021 cm²/Vs, and improving the switching property of the device from 10⁷ to 10⁴. Polyterpenol was demonstrated to have a hole transport electron blocking property, with potential applications in many organic devices, such as organic light emitting diodes. Encapsulation of biomedical devices is also proposed, given that under favourable conditions, the original chemical and biological functionality of terpinen−4−ol molecule can be preserved. Films deposited at low RF power were shown to successfully prevent adhesion and retention of several important human pathogens, including P. aeruginosa, S. aureus, and S. epidermidis, whereas films deposited at higher RF power promoted bacterial cell adhesion and biofilm formation. Preliminary investigations into in vitro biocompatibility of polyterpenol demonstrated the coating to be non−toxic for several types of eukaryotic cells, including Balb/c mice macrophage and human monocyte type (HTP−1 non-adherent) cells. Applied to magnesium substrates, polyterpenol encapsulating layer significantly slowed down in vitro biodegradation of the metal, thus increasing the viability and growth of HTP−1 cells. Recently, applied to varied nanostructured titanium surfaces, polyterpenol thin films successfully reduced attachment, growth, and viability of P. aeruginosa and S. aureus.

Influence of interleukin-1 beta on platelet-poor plasma clot formation: A potential impact on early bone healing

Objectives Hematoma quality (especially the fibrin matrix) plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β) on fibrin clot formation from platelet-poor plasma (PPP). Methods Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG), blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM), confocal microscopy (CM), turbidity, and clot lysis assays. Results The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β) compared to the control group without IL-1β (543.8 ± 205.8). Maximal turbidity was observed in the control group. IL-1β (500 pg/mL) treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05). The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers. Conclusion IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

The perfect corporate fit: New knowledge for new times

This study examines the impact of corporate practice on schooling and on teachers' professional development at the end of the millennium. It is argued that the production of new forms of knowledge is creating new sites of struggle over who owns educational knowledge, and this has profound implications for professional identity formation in all areas of social and economic endeavour, including education. As schools are re-shaped into corporations, school administrators and teachers are under increasing pressure to improve their productivity and to develop themselves as enterprising leaders and managers. To do so they are drawing more and more heavily on the growing non-academic literature of selfimprovement and self-development. Concern is expressed that such literature tends to value mindless optimism over radical doubt.