Intranasal immunization with C. muridarum major outer membrane protein (MOMP) and cholera toxin elicits local production of neutralising IgA in the prostate

Successful control of sexually transmitted diseases (STDs) through vaccination will require the development of vaccine strategies that target protective immunity to both the female and male reproductive tracts (MRT). In the male, the immune privileged nature of the male reproductive tract provides a barrier to entry of serum immunoglobulins into the male reproductive ducts, thereby preventing the induction of protective immunity using conventional injectable vaccination techniques. In this study we investigated the potential of intranasal (IN) immunization to elicit anti-chlamydial immunity in BALB/c male mice. Intranasal immunization with Chlamydia muridarum major outer membrane protein (MOMP) admixed with cholera toxin (CT) resulted in high levels of MOMP-specific IgA in prostatic fluids (PF) and MOMP-specific IgA-secreting cells in the prostate. Prostatic fluid IgA inhibited in vitro infection of McCoy cells with C. muridarum. Using RT-PCR we also show that mRNA for the polymeric immunoglobulin receptor (PIgR), which transports IgA across mucosal epithelia, is expressed only in the prostate but not in other regions of the male reproductive ducts upstream of the prostate. These data suggest that using intranasal immunization to target IgA to the prostate may protect males against STDs while at the same time maintaining the state of immune privilege within the MRT.

A short-term production scheduling methodology for open-pit mines

A multi-resource multi-stage scheduling methodology is developed to solve short-term open-pit mine production scheduling problems as a generic multi-resource multi-stage scheduling problem. It is modelled using essential characteristics of short-term mining production operations such as drilling, sampling, blasting and excavating under the capacity constraints of mining equipment at each processing stage. Based on an extended disjunctive graph model, a shifting-bottleneck-procedure algorithm is enhanced and applied to obtain feasible short-term open-pit mine production schedules and near-optimal solutions. The proposed methodology and its solution quality are verified and validated using a real mining case study.

Nonlinear pre-fire and post-fire analysis of steel frames

A numerical procedure based on the plastic hinge concept for study of the structural behaviour of steel framed structures exposed to fire is described. Most previous research on fire analysis considered the structural performance due to rising temperature. When strain reversal occurs during the cooling phase, the stress–strain curve is different. The plastic deformation is incorporated into the stress–strain curve to model the strain reversal effect in which unloading under elastic behaviour is allowed. This unloading response is traced by the incremental–iterative Newton–Raphson method. The mechanical properties of the steel member in the present fire analysis follows both Eurocode 3 Part 1.2 and BS5950 Part 8, which implicitly allow for thermal creep deformation. This paper presents an efficient fire analysis procedure for predicting thermal and cooling effects on an isolated element and a multi-storey frame. Several numerical and experimental examples related to structural behaviour in cooling phase are studied and compared with results obtained by other researchers. The proposed method is effective in the fire safety design and analysis of a building in a real fire scenario. The scope of investigation is of great significance since a large number of rescuers would normally enter a fire site as soon as the fire is extinguished and during the cooling phase, so a structural collapse can be catastrophic.

Interleukin-1β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism

One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent.

Interleukin-1beta induces human proximal tubule cell injury, alpha-smooth muscle actin expression and fibronectin production

BACKGROUND Tubulointerstitial lesions, characterized by tubular injury, interstitial fibrosis and the appearance of myofibroblasts, are the strongest predictors of the degree and progression of chronic renal failure. These lesions are typically preceded by macrophage infiltration of the tubulointerstitium, raising the possibility that these inflammatory cells promote progressive renal disease through fibrogenic actions on resident tubulointerstitial cells. The aim of the present study, therefore, was to investigate the potentially fibrogenic mechanisms of interleukin-1beta (IL-1beta), a macrophage-derived pro-inflammatory cytokine, on human proximal tubule cells (PTC). METHODS Confluent, quiescent, passage 2 PTC were established in primary culture from histologically normal segments of human renal cortex (N = 11) and then incubated in serum- and hormone-free media supplemented with either IL-1beta (0 to 4 ng/mL) or vehicle (control). RESULTS IL-1beta significantly enhanced fibronectin secretion by up to fourfold in a time- and concentration-dependent fashion. This was accompanied by significant (2.5- to 6-fold) increases in alpha-smooth muscle actin (alpha-SMA) expression, transforming growth factor beta (TGF-beta1) secretion, nitric oxide (NO) production, NO synthase 2 (NOS2) mRNA and lactate dehydrogenase (LDH) release. Cell proliferation was dose-dependently suppressed by IL-1beta. NG-methyl-l-arginine (L-NMMA; 1 mmol/L), a specific inhibitor of NOS, blocked NO production but did not alter basal or IL-1beta-stimulated fibronectin secretion. In contrast, a pan-specific TGF-beta neutralizing antibody significantly blocked the effects of IL-1beta on PTC fibronectin secretion (IL-1beta, 268.1 +/- 30.6 vs. IL-1beta+alphaTGF-beta 157.9 +/- 14.4%, of control values, P < 0.001) and DNA synthesis (IL-1beta 81.0 +/- 6.7% vs. IL-1beta+alphaTGF-beta 93.4 +/- 2.1%, of control values, P < 0.01). CONCLUSION IL-1beta acts on human PTC to suppress cell proliferation, enhance fibronectin production and promote alpha-smooth muscle actin expression. These actions appear to be mediated by a TGF-beta1 dependent mechanism and are independent of nitric oxide release.

InsulLiving house post-occupancy energy performance report

This research was commissioned by Metecno Pty Ltd, trading as Bondor®. The InsulLiving house was designed and constructed by Bondor®. The house instrumentation (electricity circuits, indoor environment, weather station) was provided by Bondor and supplied and installed by independent contractors. This report contains analysis of data collected from the InsulLiving house at Burpengary during 1 year of occupancy by a family of four for the period 1 April 2012 – 31 March 2013. The data shows a daily average electricity consumption 48% less than the regional average. The analysis confirms that the 9 star house performed thermally slightly better than the simulated performance. The home was 'near zero energy', with its modest 2.1kW solar power system meeting all of the needs for space heating and cooling, lighting and most water heating.

Alcohol ingestion impairs maximal post-exercise rates of myofibrillar protein synthesis following a single bout of concurrent training

Introduction The culture in many team sports involves consumption of large amounts of alcohol after training/competition. The effect of such a practice on recovery processes underlying protein turnover in human skeletal muscle are unknown. We determined the effect of alcohol intake on rates of myofibrillar protein synthesis (MPS) following strenuous exercise with carbohydrate (CHO) or protein ingestion. Methods In a randomized cross-over design, 8 physically active males completed three experimental trials comprising resistance exercise (8×5 reps leg extension, 80% 1 repetition maximum) followed by continuous (30 min, 63% peak power output (PPO)) and high intensity interval (10×30 s, 110% PPO) cycling. Immediately, and 4 h post-exercise, subjects consumed either 500 mL of whey protein (25 g; PRO), alcohol (1.5 g·kg body mass−1, 12±2 standard drinks) co-ingested with protein (ALC-PRO), or an energy-matched quantity of carbohydrate also with alcohol (25 g maltodextrin; ALC-CHO). Subjects also consumed a CHO meal (1.5 g CHO·kg body mass−1) 2 h post-exercise. Muscle biopsies were taken at rest, 2 and 8 h post-exercise. Results Blood alcohol concentration was elevated above baseline with ALC-CHO and ALC-PRO throughout recovery (P<0.05). Phosphorylation of mTORSer2448 2 h after exercise was higher with PRO compared to ALC-PRO and ALC-CHO (P<0.05), while p70S6K phosphorylation was higher 2 h post-exercise with ALC-PRO and PRO compared to ALC-CHO (P<0.05). Rates of MPS increased above rest for all conditions (~29–109%, P<0.05). However, compared to PRO, there was a hierarchical reduction in MPS with ALC-PRO (24%, P<0.05) and with ALC-CHO (37%, P<0.05). Conclusion We provide novel data demonstrating that alcohol consumption reduces rates of MPS following a bout of concurrent exercise, even when co-ingested with protein. We conclude that alcohol ingestion suppresses the anabolic response in skeletal muscle and may therefore impair recovery and adaptation to training and/or subsequent performance.

Ownership, corporate governance and IPO post-listing liquidity

This thesis investigates how ownership structure and corporate governance relate to the post-listing liquidity of IPO firms. Using a sample of 1,049 Chinese IPOs from 2001 to 2010, the results show firms with a broader shareholder base and higher ownership concentration have greater post-listing liquidity. So do firms with higher state ownership and lower institution ownership. Corporate governance is also important; post-listing liquidity is higher for firms with CEO duality, a larger and more independent board, and more frequent board meetings. The 2005 Split Share Structure Reform, which increased the proportion of tradable shares, has a positive impact on liquidity.

Talk about a YouTube video in preschool : the mutual production of shared understanding for learning with digital technology

Much of what is written about digital technologies in preschool contexts focuses on young children’s acquisition of skills rather than their meaning-making during use of technologies. In this paper, we consider how the viewing of a YouTube video was used by a teacher and children to produce shared understandings about it. Conversation analysis of talk and interaction during the viewing of the video establishes some of the ways that individual accounts of events were produced for others and then endorsed as shared understandings. The analysis establishes how adults and children made use of verbal and embodied actions during interactions to produce shared understandings of the YouTube video, the events it recorded and written commentary about those events

IL-23R is epigenetically regulated and modulated by chemotherapy in non-small cell lung cancer

The Interleukin-23 (IL-23)/IL-23R signaling axis is an important inflammatory pathway, involved in the stimulation and regulation of the T helper (Th) 17 lymphocytes, resulting in the production of IL-17. Aside from auto-immunity, this cytokine has also been linked to carcinogenesis and polymorphisms in the IL-23R gene are associated with an increased risk for the development of a number of different cancers. Activation of the IL-23 pathway results in the up-regulation of STAT3 and it is thought that the pathological consequences associated with this are in part due to the production of IL-17. We have previously identified IL-23A as pro-proliferative and epigenetically regulated in non-small cell lung cancer (NSCLC). The current study aims to evaluate IL-23R in greater detail in NSCLC. We demonstrate that IL-23R is expressed and epigenetically regulated in NSCLC through histone post-translation modifications and CpG island methylation. In addition, Gemcitabine treatment, a chemotherapy drug used in the treatment of NSCLC, resulted in the up-regulation of the IL-23R. Furthermore, Apilimod (STA 5326), a small molecule which blocks the expression of IL-23 and IL-12, reduced the proliferative capacity of NSCLC cells, particularly in the adenocarcinoma (A549) sub-type. Apilimod is currently undergoing investigation in a number of clinical trials for the treatment of auto-immune conditions such as Crohn's disease and Rheumatoid Arthritis. Our results may have implications for treating NSCLC patients with Gemcitabine or epigenetic targeted therapies. However, Apilimod may possibly provide a new treatment avenue for NSCLC patients. Work is currently ongoing to further delineate the IL-23/IL-23R axis in this disease.

Music production in times of monopoly : the example of Sweden

For several decades now, Sweden has been successful in the worldwide popular music arena. This article explores how Sweden, as an integral part of the global music industry, has been able to cope with the changed market conditions brought about by regulatory changes and digital technologies. The article reflects on the virtualization of music distribution, the decline of the long‐play album and the ageing popular music audience.

Literacies on the Web : Co-Production of Literary Texts on Fan Fiction Sites

In this chapter the authors discuss and informal learning settings such as fan fiction sites and their relations to teaching and learning within formal learning settings. Young people today spend a lot of time with social media built on user generated content. These media are often characterized by participatory culture which offers a good environment for developing skills and identity work. In this chapter the authors problematize fan fiction sites as informal learning settings where the possibilities to learn are powerful and significant. They also discuss the learning processes connected to the development of literacies. Here the rhetoric principle of “imitatio” plays a vital part as well as the co-production of texts on the sites, strongly supported by the beta reader and the power of positive feedback. They also display that some fans, through the online publication of fan fiction, are able to develop their craft in a way which previously have been impossible.

A Review On The Production Of Levulinic Acid And Furanics From Sugars

Sugarcane products represent an abundant and relatively low cost carbon resource that can be utilised to produce chemical intermediates such as levulinic acid and furanics. These chemicals can be easily upgraded to commodity and specialty chemicals and biofuels by high yielding and well established technologies. However, there are challenges and technical hurdles that need to be overcome before these chemical intermediates can be cost-effectively produced in commercial quantities. The paper reviews production of levulinic acid and furanics from sugars by homogeneous mineral acid catalysts, and reports on preliminary studies on the production of these compounds with environmentally friendly biodegradable sulfonic acids. The yields (>50% of theoretical) of levulinic acid, formic acid and furfural obtained with these organic acids are comparable to that of sulphuric acid currently used for their production.

The next publication revolution : open access and the post-2014 Research Excellence Framework

The world is increasingly moving towards more open models of publishing and communication. The UK government has demonstrated a firm commitment to ensuring that academic research outputs are made available to all who might benefit from access to them, and its open access policy attempts to make academic publications freely available to readers, rather than being locked behind pay walls or only available to researchers with access to well-funded university libraries. Open access policies have an important role to play in fostering an open innovation ecosystem and ensuring that maximum value is derived from investments in university-based research. But are we ready to embrace this change?

Sounds From The Empty City (soundtrack)

These wordless songs were composed as music first, and soundtrack second. There is a difference. A soundtrack will always be connected with whatever it is accompanying. Music doesn’t neccessarily need to reference anything else. The Empty City transformed a picture book into a non-verbal performance combining the live and animated. Without spoken words the show would dance on the dangerous intersection of music, image and action. In both theatre and film (and this production drew on both traditions) soundtrack and music are often added on at the end when everything’s been pre-determined, a passive, responsive mode for such a powerful artform. It’s literally added in ‘post’. In The Empty City, music was present from its inception and grew with the show. It was active in process and product. It frequently led rehearsals and shaped other key decisions in virtual and live performance. Rather than tailor-make music towards pre-determined moments, independent compositions created without specific reference to narrative experimented with the creation of a flock of small musical pieces. I was interested in seeing how they flew and where they roosted, rather than having them born and raised in (narrative) captivity. The sonic palette is largely acoustic, incorporating ukulele, prepared piano and supported by a range of other elements tending towards electronica. Eventually more than seventy pieces of music were made for this show, twice the number used. These pieces were then placed in relation to the emerging scenes, then adapted in duration, texture and progression to develop a relationship with the scene. In this way, music (even when it’s synced) has a conversation with a performance, an exchange that may result in surprise rather than fulfillment of expectation. Leitmotif emerged from loops and layers, as the pieces of music ‘conversed’ with each other, rather than being premeditated and imposed. Nineteen of these tracks are compiled for this release, which finds the compositions (which progressed through many versions) poised at the moment between their fullest iteration as ‘music’ and their editing and full incorporation into a sychronised soundtrack. They are released as the began: as 'music-alone' (Kivy) In picture-book writing, the mutual interplay of text and image is sometimes referred to as interanimation , and this is the kind of symbiosis this project sought in the creation of the soundtrack. Reviewers of the noted the important role of the soundtrack in two separate productions of The Empty City: “The original score…takes centre stage” (Borhani, 2013) “…swept up in its repetition of sounds and images, like a Bach fugue” (Zampatti, 2013)