Changes in neutrophil surface receptor expression, degranulation, and respiratory burst activity after moderate- and high-intensity exercise

Intense exercise stimulates the systemic release of a variety of factors that alter neutrophil surface receptor expression and functional activity. These alterations may influence resistance to infection after intense exercise. The aim of this study was to examine the influence of exercise intensity on neutrophil receptor expression, degranulation (measured by plasma and intracellular myeloperoxidase concentrations), and respiratory burst activity. Ten well-trained male runners ran on a treadmill for 60 min at 60% [moderate-intensity exercise (MI)] and 85% maximal oxygen consumption [high-intensity exercise (HI)]. Blood was drawn immediately before and after exercise and at 1 h postexercise. Immediately after HI, the expression of the neutrophil receptor CD16 was significantly below preexercise values (P < 0.01), whereas MI significantly reduced CD35 expression below preexercise values (P < 0.05). One hour after exercise at both intensities, there was a significant decline in CD11b expression (P < 0.05) and a further decrease in CD16 expression compared with preexercise values (P < 0.01). CD16 expression was lower 1 h after HI than 1 h after MI (P < 0.01). Immediately after HI, intracellular myeloperoxidase concentration was less than preexercise values (P < 0.01), whereas plasma myeloperoxidase concentration was greater (P < 0.01), indicating that HI stimulated neutrophil degranulation. Plasma myeloperoxidase concentration was higher immediately after HI than after MI (P < 0.01). Neutrophil respiratory burst activity increased after HI (P < 0.01). In summary, both MI and HI reduced neutrophil surface receptor expression. Although CD16 expression was reduced to a greater extent after HI, this reduction did not impair neutrophil degranulation and respiratory burst activity.

Labor market reform and the changing structure of wage determination in China's state sector during the 1980s

China's market-oriented labor market reform has been in place for about one and a half decades. This study uses individual data for 1981 and 1987 to examine the success of the first half of the reform program. Success is evaluated by examining changes in the wage setting structure in the state-owned sector over the reform period. Have the market reforms stimulated worker incentives by increasing the returns to human capital acquisition? Has the wage structure altered to more closely mimic that of a market economy? In 1987, there is evidence of a structural change in the system of wage determination, with slightly increased rates of return to human capital. However, changes in industrial wage differentials appear to play the dominant role. It is argued that this may be due to labor market reforms, in particular the introduction of the profit related bonus scheme.J. Comp. Econom.,December 1997,25(3), pp. 403–421. Australian National University, Canberra, ACT0200, Australia and University of Tasmania, Hobart, Tasmania, Australia, and University of Aberdeen, Old Aberdeen, Scotland AB24 3QY.

The ionic products from bredigite bioceramics induced cementogenic differentiation of periodontal ligament cells via activation of the Wnt/β-catenin signalling pathway

Periodontitis results from the destructive inflammatory reaction of the host elicited by a bacterial biofilm adhering to the tooth surface and if left untreated, may lead to the loss of the teeth and the surrounding tissues, including the alveolar bone. Cementum is a specialized calcified tissue covering the tooth root and an essential part of the periodontium which enables the attachment of the periodontal ligament to the root and the surrounding alveolar bone. Periodontal ligament cells (PDLCs) represent a promising cell source for periodontal tissue engineering. Since cementogenesis is the critical event for the regeneration of periodontal tissues, this study examined whether inorganic stimuli derived from bioactive bredigite (Ca7MgSi4O16) bioceramics could stimulate the proliferation and cementogenic differentiation of PDLCs, and further investigated the involvement of the Wnt/β-catenin signalling pathway during this process via analysing gene/protein expression of PDLCs which interacted with bredigite extracts. Our results showed that the ionic products from bredigite powder extracts led to significantly enhanced proliferation and cementogenic differentiation, including mineralization–nodule formation, ALP activity and a series of bone/cementum-related gene/protein expression (ALP, OPN, OCN, BSP, CAP and CEMP1) of PDLCs in a concentration dependent manner. Furthermore, the addition of cardamonin, a Wnt/β-catenin signalling inhibitor, reduced the pro-cementogenesis effect of the bredigite extracts, indicating the involvement of the Wnt/β-catenin signalling pathway in the cementogenesis of PDLCs induced by bredigite extracts. The present study suggests that an entirely inorganic stimulus with a specific composition of bredigite bioceramics possesses the capacity to trigger the activation of the Wnt/β-catenin signalling pathway, leading to stimulated differentiation of PDLCs toward a cementogenic lineage. The results indicate the therapeutic potential of bredigite ceramics in periodontal tissue engineering application.

A practical comparison of manual and autonomous methods for acoustic monitoring

1. Autonomous acoustic recorders are widely available and can provide a highly efficient method of species monitoring, especially when coupled with software to automate data processing. However, the adoption of these techniques is restricted by a lack of direct comparisons with existing manual field surveys. 2. We assessed the performance of autonomous methods by comparing manual and automated examination of acoustic recordings with a field-listening survey, using commercially available autonomous recorders and custom call detection and classification software. We compared the detection capability, time requirements, areal coverage and weather condition bias of these three methods using an established call monitoring programme for a nocturnal bird, the little spotted kiwi(Apteryx owenii). 3. The autonomous recorder methods had very high precision (>98%) and required <3% of the time needed for the field survey. They were less sensitive, with visual spectrogram inspection recovering 80% of the total calls detected and automated call detection 40%, although this recall increased with signal strength. The areal coverage of the spectrogram inspection and automatic detection methods were 85% and 42% of the field survey. The methods using autonomous recorders were more adversely affected by wind and did not show a positive association between ground moisture and call rates that was apparent from the field counts. However, all methods produced the same results for the most important conservation information from the survey: the annual change in calling activity. 4. Autonomous monitoring techniques incur different biases to manual surveys and so can yield different ecological conclusions if sampling is not adjusted accordingly. Nevertheless, the sensitivity, robustness and high accuracy of automated acoustic methods demonstrate that they offer a suitable and extremely efficient alternative to field observer point counts for species monitoring.

Iris based identity verification robust to sample presentation security attacks

Iris based identity verification is highly reliable but it can also be subject to attacks. Pupil dilation or constriction stimulated by the application of drugs are examples of sample presentation security attacks which can lead to higher false rejection rates. Suspects on a watch list can potentially circumvent the iris based system using such methods. This paper investigates a new approach using multiple parts of the iris (instances) and multiple iris samples in a sequential decision fusion framework that can yield robust performance. Results are presented and compared with the standard full iris based approach for a number of iris degradations. An advantage of the proposed fusion scheme is that the trade-off between detection errors can be controlled by setting parameters such as the number of instances and the number of samples used in the system. The system can then be operated to match security threat levels. It is shown that for optimal values of these parameters, the fused system also has a lower total error rate.

Business model experimentation : what is the role of deign-led prototyping in developing novel business models?

This book presents readers with the opportunity to fundamentally re-evaluate the processes of innovation and entrepreneurship, and to rethink how they might best be stimulated and fostered within our organizations and communities. The fundamental thesis of the book is that the entrepreneurial process is not a linear progression from novel idea to successful innovation, but is an iterative series of experiments, where progress depends on the persistence and resilience of the individuals involved, and their ability and to learn from failure as well as success. From this premise, the authors argue that the ideal environment for new venture creation is a form of “experimental laboratory,” a community of innovators where ideas are generated, shared, and refined; experiments are encouraged; and which in itself serves as a test environment for those ideas and experiments. This environment is quite different from the traditional “incubator,” which may impose the disciplines of the established firm too early in the development of the new venture.

Book Review [White Bound: Nationalists, Antiracists, and the Shared Meanings of Race, by MW Hughey]

Dr Kathy A. Mills provides a critical synthesis and review of the new book by Matthew W. Hughey entitle: White Bound: Nationalists, Antiractists, and the Shared Meanings of Race, published by Standford University Press in 2012. A sample of Dr Mills' review reads: "The author positions race squarely at the center to challenge the shared assumptions of white supremacist logic on both sides of the debate. The clever thesis blurs the boundaries between “good whites” and “bad whites”, rendering the white reader intellectually stimulated, but existentially unchanged – White Bound – as the author ponders: “Perhaps we have met the enemy, and he [it] is us” (p.193)...The unanswered question that remains is: How do we resist the various “shades” of white supremacy to pursue counter-hegemonic practices?"

Determining process model precision and generalization with weighted artificial negative events

Process mining encompasses the research area which is concerned with knowledge discovery from event logs. One common process mining task focuses on conformance checking, comparing discovered or designed process models with actual real-life behavior as captured in event logs in order to assess the “goodness” of the process model. This paper introduces a novel conformance checking method to measure how well a process model performs in terms of precision and generalization with respect to the actual executions of a process as recorded in an event log. Our approach differs from related work in the sense that we apply the concept of so-called weighted artificial negative events towards conformance checking, leading to more robust results, especially when dealing with less complete event logs that only contain a subset of all possible process execution behavior. In addition, our technique offers a novel way to estimate a process model’s ability to generalize. Existing literature has focused mainly on the fitness (recall) and precision (appropriateness) of process models, whereas generalization has been much more difficult to estimate. The described algorithms are implemented in a number of ProM plugins, and a Petri net conformance checking tool was developed to inspect process model conformance in a visual manner.

Automated marine mammal detection from aerial imagery

This paper presents two algorithms to automate the detection of marine species in aerial imagery. An algorithm from an initial pilot study is presented in which morphology operations and colour analysis formed the basis of its working principle. A second approach is presented in which saturation channel and histogram-based shape profiling were used. We report on performance for both algorithms using datasets collected from an unmanned aerial system at an altitude of 1000 ft. Early results have demonstrated recall values of 48.57% and 51.4%, and precision values of 4.01% and 4.97%.

The development of an effective vaccine against Chlamydia : utilisation of a non-toxic mucosal adjuvant to generate a protective mucosal response

Chlamydia is responsible for a wide range of diseases with enormous global economic and health burden. As the majority of chlamydial infections are asymptomatic, a vaccine has greatest potential to reduce infection and disease prevalence. Protective immunity against Chlamydia requires the induction of a mucosal immune response, ideally, at the multiple sites in the body where an infection can be established. Mucosal immunity is most effectively stimulated by targeting vaccination to the epithelium, which is best accomplished by direct vaccine application to mucosal surfaces rather than by injection. The efficacy of needle-free vaccines however is reliant on a powerful adjuvant to overcome mucosal tolerance. As very few adjuvants have proven able to elicit mucosal immunity without harmful side effects, there is a need to develop non-toxic adjuvants or safer ways to administered pre-existing toxic adjuvants. In the present study we investigated the novel non-toxic mucosal adjuvant CTA1-DD. The immunogenicity of CTA1-DD was compared to our "gold-standard" mucosal adjuvant combination of cholera toxin (CT) and cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN). We also utilised different needle-free immunisation routes, intranasal (IN), sublingual (SL) and transcutaneous (TC), to stimulate the induction of immunity at multiple mucosal surfaces in the body where Chlamydia are known to infect. Moreover, administering each adjuvant by different routes may also limit the toxicity of the CT/CpG adjuvant, currently restricted from use in humans. Mice were immunised with either adjuvant together with the chlamydial major outer membrane protein (MOMP) to evaluate vaccine safety and quantify the induction of antigen-specific mucosal immune responses. The level of protection against infection and disease was also assessed in vaccinated animals following a live genital or respiratory tract infectious challenge. The non-toxic CTA1-DD was found to be safe and immunogenic when delivered via the IN route in mice, inducing a comparable mucosal response and level of protective immunity against chlamydial challenge to its toxic CT/CpG counterpart administered by the same route. The utilisation of different routes of immunisation strongly influenced the distribution of antigen-specific responses to distant mucosal surfaces and also abrogated the toxicity of CT/CpG. The CT/CpG-adjuvanted vaccine was safe when administered by the SL and TC routes and conferred partial immunity against infection and pathology in both challenge models. This protection was attributed to the induction of antigen-specific pro-inflammatory cellular responses in the lymph nodes regional to the site of infection and rather than in the spleen. Development of non-toxic adjuvants and effective ways to reduce the side effects of toxic adjuvants has profound implications for vaccine development, particularly against mucosal pathogens like Chlamydia. Interestingly, we also identified two contrasting vaccines in both infection models capable of preventing infection or pathology exclusively. This indicated that the development of pathology following an infection of vaccinated animals was independent of bacterial load and was instead the result of immunopathology, potentially driven by the adaptive immune response generated following immunisation. While both vaccines expressed high levels of interleukin (IL)-17 cytokines, the pathology protected group displayed significantly reduced expression of corresponding IL-17 receptors and hence an inhibition of signalling. This indicated that the balance of IL-17-mediated responses defines the degree of protection against infection and tissue damage generated following vaccination. This study has enabled us to better understand the immune basis of pathology and protection, necessary to design more effective vaccines.

Young people, public space and new urbanism

The first of three articles in this issue addressing the public space topic considers public space and young people in the light of a range of papers delivered at the 27th International Conference on 'Making Cities Livable', held in Vienna, Austria, in July 2000. Under the overarching concept of the "liveable city" the conference themes of 'Rediscovery of public space' and 'Cities for the wellbeing of children' attracted a broad mix of those interested in the planning, design and management of urban space. A number of themes percolated through the conference which stimulated the writers to examine the nexus between urban development, young people and public space. There is an ongoing need to examine the meaning of public space in the face of powerful urban development trends. A model of public space practice is required which incorporates a vision of inclusive public spaces, fosters the interactivity of design, planning, social policy and management, and resources for greater communication and strategic action between stake holders from the most local of levels to those at state and international levels. The speed and magnitude of contemporary urban development makes community input and influence difficult, particularly for those impacted on by the exclusionary tendencies of much urban development. It is critical that a range of meaningful and sustainable mechanisms are developed which allow young people’s conceptions of what constitutes youth-friendly space to be directly made and taken account of.

Limbal mesenchymal stromal cells (L-MSC) display immunosuppressive properties across donor and species boundaries

Purpose: We have evaluated the immunosuppressive properties of L-MSC with the view to using these cells in allogeneic cell therapies for corneal disorders. We hypothesized that L-MSC cultures would suppress T-cell activation, in a similar way to those established from human bone marrow (BM-MSC). Methods: MSC cultures were established from the limbal stroma of cadaveric donor eye tissue (up to 1 week postmortem) using either conventional serum-supplemented growth medium or a commercial serum-free medium optimized for bone marrow derived MSC (MesenCult-XF system). The MSC phenotype was examined by flow cytometry according to current and emerging markers for human MSC. Immunosuppressive properties were assessed using a mixed lymphocyte reaction (MLR) assay, whereby the white cell fraction from two immunologically incompatible blood donors are cultured together in direct contact with growth arrested MSC. T-cell activation (proliferation) was measured by uptake of tritiated thymidine. Human L-MSC were tested in parallel with human BM-MSC and rabbit L-MSC. Human and rabbit L-MSC were also tested for their ability to stimulate the growth of limbal epithelial (LE) cells in colony formation assays (for both human as well as rabbit LE cells). Results: L-MSC cultures were >95% negative for CD34, CD45 and HLA-DR and positive for CD73, CD90, CD105 and HLA-ABC. Modest levels (30%) of CD146 expression were observed for L-MSC cultures grown in serum-supplemented growth medium, but not those grown in MesenCult-XF. All MSC cultures derived from both human and rabbit tissue suppressed T-cell activation to varying degrees according to culture technique and species (MesenCult-XF >> serum-fed cultures, rabbit L-MSC >> human L-MSC). All L-MSC stimulated colony formation by LE cells irrespectively of the combination of cell species used. Conclusions: L-MSC display immunosuppressive qualities, in addition to their established non-immunogenic cell surface marker profile, and stimulate LE cell growth in vitro across species boundaries. These results support the potential use of allogeneic or even xenogeneic L-MSC in the treatment of corneal disorders.

A pattern based two-stage text classifier

In a classification problem typically we face two challenging issues, the diverse characteristic of negative documents and sometimes a lot of negative documents that are closed to positive documents. Therefore, it is hard for a single classifier to clearly classify incoming documents into classes. This paper proposes a novel gradual problem solving to create a two-stage classifier. The first stage identifies reliable negatives (negative documents with weak positive characteristics). It concentrates on minimizing the number of false negative documents (recall-oriented). We use Rocchio, an existing recall based classifier, for this stage. The second stage is a precision-oriented “fine tuning”, concentrates on minimizing the number of false positive documents by applying pattern (a statistical phrase) mining techniques. In this stage a pattern-based scoring is followed by threshold setting (thresholding). Experiment shows that our statistical phrase based two-stage classifier is promising.

Read classification for next generation sequencing

Next Generation Sequencing (NGS) has revolutionised molec- ular biology, allowing routine clinical sequencing. NGS data consists of short sequence reads, given context through downstream assembly and annotation, a process requiring reads consistent with the assumed species or species group. The common bacterium Staphylococcus aureus may cause severe and life-threatening infections in humans, with some strains exhibiting antibiotic resistance. Here we apply an SVM classifier to the important problem of distinguishing S. aureus sequencing projects from other pathogens, including closely related Staphylococci. Using a sequence k-mer representation, we achieve precision and recall above 95%, implicating features with important functional associations.

In vitro functional characterisation of IGF-I : VN-induced breast cancer progression

Members of the insulin-like growth factor (IGF) family have been shown to play critical roles in normal growth and development, as well as in tumour biology. The IGF system is complex and the biological effects of the IGFs are determined by their diverse interactions between many molecules, including their interactions with extracellular matrix (ECM) proteins. Recent studies have demonstrated that IGFs associate with the ECM protein vitronectin (VN) through IGF-binding proteins (IGFBP) and that this interaction modulates IGF-stimulated biological functions, namely cell migration and cell survival through the cooperative involvement of the type-I IGF receptor (IGF-1R) and VN-binding integrins. Since IGFs play important roles in the transformation and progression of breast cancer and VN has been found to be over-expressed at the leading edge of breast tumours, this project aimed to describe the effects of IGF-I:VN interactions on breast cell function. This was undertaken to dissect the molecular mechanisms underlying IGF-I:VN-induced responses and to design inhibitors to block the effects of such interactions. The studies described herein demonstrate that the increase in migration of MCF-7 breast cancer cells in response to the IGF-I:IGFBP-5:VN complex is accompanied by differential expression of genes known to be involved in migration, invasion and/or survival, including Tissue-factor (TF), Stratifin (SFN), Ephrin-B2, Sharp-2 and PAI-1. This „migration gene signature‟ was confirmed using real-time PCR analysis. Substitution of the native IGF-I within the IGF-I:IGFBP:VN complex with the IGF-I analogue, \[L24]\[A31]-IGF-I, which has a reduced affinity for the IGF-1R, failed to stimulate cell migration and interestingly, also failed to induce the differential gene expression. This supports the involvement of the IGF-1R in mediating these changes in gene expression. Furthermore, lentiviral shRNA-mediated stable knockdown of TF and SFN completely abrogated the increased cell migration induced by IGF-I:IGFBP:VN complexes in MCF-7 cells. Indeed, when these cells were grown in 3D Matrigel™ cultures a decrease in the overall size of the 3D spheroids in response to the IGF-I:IGFBP:VN complexes was observed compared to the parental MCF-7 cells. This suggests that TF and SFN have a role in complex-stimulated cell survival. Moreover, signalling studies performed on cells with the reduced expression of either TF or SFN had a decreased IGF-1R activation, suggesting the involvement of signalling pathways downstream of IGF-1R in TF- and/or SFN-mediated cell migration and cell survival. Taken together, these studies provide evidence for a common mechanism activated downstream of the IGF-1R that induces the expression of the „migration gene signature‟ in response to the IGF-I:IGFBP:VN complex that confers breast cancer cells the propensity to migrate and survive. Given the functional significance of the interdependence of ECM and growth factor (GF) interactions in stimulating processes key to breast cancer progression, this project aimed at developing strategies to prevent such growth factor:ECM interactions in an effort to inhibit the downstream functional effects. This may result in the reduction in the levels of ECM-bound IGF-I present in close proximity to the cells, thereby leading to a reduction in the stimulation of IGF-1R present on the cell surface. Indeed, the inhibition of IGF-I-mediated effects through the disruption of its association with ECM would not alter the physiological levels of IGF-I and potentially only exert effects in situations where abnormal over expression of ECM proteins are found; namely carcinomas and hyperproliferative diseases. In summary, this PhD project has identified novel, innovative and realistic strategies that can be used in vitro to inhibit the functions exerted by the IGF-I:IGFBP:VN multiprotein complexes critical for cancer progression, with a potential to be translated into in vivo investigations. Furthermore, TF and SFN were found to mediate IGF-I:IGFBP:VN-induced effects, thereby revealing their potential to be used as therapeutic targets or as predictive biomarkers for the efficacy of IGF-1R targeting therapies in breast cancer patients. In addition to its therapeutic and clinical scope, this PhD project has significantly contributed to the understanding of the role of the IGF system in breast tumour biology by providing valuable new information on the mechanistic events underpinning IGF-I:VN-mediated effects on breast cell functions. Furthermore, this is the first instance where favourable binding sites for IGF-II, IGFBP-3 and IGFBP-5 on VN have been identified. Taken together, this study has functionally characterised the interactions between IGF-I and VN and through innovative strategies has provided a platform for the development of novel therapies targeting these interactions and their downstream effects.