Different correlation of Sphingosine-1-Phosphate receptor 1 with receptor activator of nuclear factor kappa B ligand and regulatory T cells in rat periapical lesions

Introduction Sphingosine-1-phosphate receptor 1 (S1P1) is crucial for regulation of immunity and bone metabolism. This study aimed to investigate the expression of S1P1 in rat periapical lesions and its relationship with receptor activator of nuclear factor kappa B ligand (RANKL) and regulatory T (Treg) cells. Methods Periapical lesions were induced by pulp exposure in the first lower molars of 55 Wistar rats. Thirty rats were killed on days 0, 7, 14, 21, 28, and 35, and their mandibles were harvested for x-ray imaging, micro–computed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. The remaining 25 rats were killed on days 0, 14, 21, 28, and 35, and mandibles were harvested for flow cytometry. Results The volume and area of the periapical lesions increased from day 0 to day 21 and then remained comparably stable after day 28. S1P1-positive cells were observed in the inflammatory periapical regions; the number of S1P1-positive cells peaked at day 14 and then decreased from day 21 to day 35. The distribution of S1P1-positive cells was positively correlated with the dynamics of RANKL-positive cells but was negatively correlated with that of Treg cells. Conclusions S1P1 expression was differentially correlated with RANKL and Treg cell infiltration in the periapical lesions and is therefore a contributing factor to the pathogenesis of such lesions.

A technique for analysing GOOSE packets when testing relays in an IEC 61850-8-1 environment

While the implementation of the IEC 61850 standard has significantly enhanced the performance of communications in electrical substations, it has also increased the complexity of the system. Subsequently, these added elaborations have introduced new challenges in relation to the skills and tools required for the design, test and maintenance of 61850-compatible substations. This paper describes a practical experience of testing a protection relay using a non-conventional test equipment; in addition, it proposes a third party software technique to reveal the contents of the packets transferred on the substation network. Using this approach, the standard objects can be linked and interpreted to what the end-users normally see in the IED and test equipment proprietary software programs.

Formal modelling and analysis of DNP3 secure authentication

Supervisory Control and Data Acquisition (SCADA) systems are one of the key foundations of smart grids. The Distributed Network Protocol version 3 (DNP3) is a standard SCADA protocol designed to facilitate communications in substations and smart grid nodes. The protocol is embedded with a security mechanism called Secure Authentication (DNP3-SA). This mechanism ensures that end-to-end communication security is provided in substations. This paper presents a formal model for the behavioural analysis of DNP3-SA using Coloured Petri Nets (CPN). Our DNP3-SA CPN model is capable of testing and verifying various attack scenarios: modification, replay and spoofing, combined complex attack and mitigation strategies. Using the model has revealed a previously unidentified flaw in the DNP3-SA protocol that can be exploited by an attacker that has access to the network interconnecting DNP3 devices. An attacker can launch a successful attack on an outstation without possessing the pre-shared keys by replaying a previously authenticated command with arbitrary parameters. We propose an update to the DNP3-SA protocol that removes the flaw and prevents such attacks. The update is validated and verified using our CPN model proving the effectiveness of the model and importance of the formal protocol analysis.

All horticultural factsheets (Part 1)

Teaching Resource material prepared for DLB320 Landscape Horticulture, available to wider group of users via ePrints.

Vascular endothelial growth factor is an autocrine growth factor, signaling through neuropilin-1 in non-small cell lung cancer

Background The VEGF pathway has become an important therapeutic target in lung cancer, where VEGF has long been established as a potent pro-angiogenic growth factor expressed by many types of tumors. While Bevacizumab (Avastin) has proven successful in increasing the objective tumor response rate and in prolonging progression and overall survival in patients with NSCLC, the survival benefit is however relatively short and the majority of patients eventually relapse. The current use of tyrosine kinase inhibitors alone and in combination with chemotherapy has been underwhelming, highlighting an urgent need for new targeted therapies. In this study, we examined the mechanisms of VEGF-mediated survival in NSCLC cells and the role of the Neuropilin receptors in this process. Methods NSCLC cells were screened for expression of VEGF and its receptors. The effects of recombinant VEGF and its blockade on lung tumor cell proliferation and cell cycle were examined. Phosphorylation of Akt and Erk1/2 proteins was examined by high content analysis and confocal microscopy. The effects of silencing VEGF on cell proliferation and survival signaling were also assessed. A Neuropilin-1 stable-transfected cell line was generated. Cell growth characteristics in addition to pAkt and pErk1/2 signaling were studied in response to VEGF and its blockade. Tumor growth studies were carried out in nude mice following subcutaneous injection of NP1 over-expressing cells. Results Inhibition of the VEGF pathway with anti-VEGF and anti-VEGFR-2 antibodies or siRNA to VEGF, NP1 and NP2 resulted in growth inhibition of NP1 positive tumor cell lines associated with down-regulation of PI3K and MAPK kinase signaling. Stable transfection of NP1 negative cells with NP1 induced proliferation in vitro, which was further enhanced by exogenous VEGF. In vivo, NP1 over-expressing cells significantly increased tumor growth in xenografts compared to controls. Conclusions Our data demonstrate that VEGF is an autocrine growth factor in NSCLC signaling, at least in part, through NP1. Targeting this VEGF receptor may offer potential as a novel therapeutic approach and also support the evaluation of the role of NP1 as a biomarker predicting sensitivity or resistance to VEGF and VEGFR-targeted therapies in the clinical arena.

Functional and psychosocial outcomes 1 year after mild stroke

Background Mild stroke survivors are generally discharged from acute care within a few days of the stroke event, often without rehabilitation follow-up. We aimed to examine the recovery trajectory for male patients and their wife-caregivers during the 12 months postdischarge. Methods A descriptive study was undertaken to examine functional outcomes, quality of life (QOL), depression, caregiver strain, and marital function in a prospective cohort of male survivors of mild stroke and their wife-caregivers during the 12 months postdischarge. Data from each point in time were summarized and repeated measures analyses undertaken. Logistic regression was used to determine which baseline demographic and biopsychosocial variables influenced or predicted marital functioning 1 year postdischarge. Results A total of 38 male patients (mean age 63.4 years) and their wife-caregivers (mean age 58.5 years) were examined. The median discharge National Institutes of Health Stroke Scale score was 1.5, modified Rankin Scale score was 1.0, Barthel Index was 100.0, and Stroke Impact Scale-16v2 score was 78.5. The patients' modified Rankin Scale (function) and QOL scores improved significantly over time (F (2) = 4.583, P = .017; and F (6) = 5.632, P < .001, respectively). However, the wife-caregiver QOL scores did not change. Multivariate analysis revealed overall worsening of depression for both the patient and wife-caregivers (F (6, 32) = 3.087, P = .017) and marital function (F (6, 32) = 3.961, P = .004), although the wife-caregivers' perceptions of caregiver strain improved (F (6, 32) = 3.923, P = .007). None of the measured variables were associated with marital functioning 1 year postdischarge. Conclusions Despite improvement in patients' functional status, other patient and wife-caregiver psychosocial outcomes during the 12 months postdischarge may be negatively affected. Thus, attention needs to focus on recovery beyond functional outcomes.

The sweet aroma of success: Modification of products for new markets in the case of TORQ by Di Bella Coffee

In 2002, Phillip Di Bella’s childhood passion for coffee and keen entrepreneurial spirit led him to establish a small coffee roasting warehouse in in the inner suburbs of Brisbane (Di Bella, 2012). With a keen sense of direction and passion for his coffee products and providing unparalleled customer service, Di Bella Coffee quickly grew to become a key player in the coffee roasting scene. This passion for the ultimate coffee experience is evident in the firm’s logo ‘Di Bella Coffee Inspires Passion’. Phillip Di Bella stated that ‘the common denominator of this company is about inspiration and passion. We are not a coffee company, we are a people company. You know, are we inspiring you from the moment you walk in the door to the moment you leave. If you are not feeling inspired then we haven’t done our job properly as a company’. Fundamentally, providing the ultimate coffee experience, as detailed in the following case is one in which focuses on the coffee consumption experience, not the coffee itself. Over that last 10 years Di Bella Coffee has constantly strived for the ultimate coffee, while expanding business operations into the booming Asian coffee market, establishing headquarters in Shanghai in 2010. In 2011, Di Bella Coffee commenced their second international venture with the launch of operations in India (Di Bella Coffee, 2012); followed shortly by the creation of a new category of coffee, set to revolutionise to coffee industry. The fusion of two traditional forms of coffee; espresso coffee and instant coffee, to create a third category- espresso instant, led to the development of TORQ by Di Bella.

Substrate effects in the supramolecular assembly of 1,3,5-benzene tricarboxylic acid on graphite and graphene

The behavior of small molecules on a surface depends critically on both molecule–substrate and intermolecular interactions. We present here a detailed comparative investigation of 1,3,5-benzene tricarboxylic acid (trimesic acid, TMA) on two different surfaces: highly oriented pyrolytic graphite (HOPG) and single-layer graphene (SLG) grown on a polycrystalline Cu foil. On the basis of high-resolution scanning tunnelling microscopy (STM) images, we show that the epitaxy matrix for the hexagonal TMA chicken wire phase is identical on these two surfaces, and, using density functional theory (DFT) with a non-local van der Waals correlation contribution, we identify the most energetically favorable adsorption geometries. Simulated STM images based on these calculations suggest that the TMA lattice can stably adsorb on sites other than those identified to maximize binding interactions with the substrate. This is consistent with our net energy calculations that suggest that intermolecular interactions (TMA–TMA dimer bonding) are dominant over TMA–substrate interactions in stabilizing the system. STM images demonstrate the robustness of the TMA films on SLG, where the molecular network extends across the variable topography of the SLG substrates and remains intact after rinsing and drying the films. These results help to elucidate molecular behavior on SLG and suggest significant similarities between adsorption on HOPG and SLG.

Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1β (IL-1β) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1β secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

The Value of Financial Planning Advice: Process and Outcome Effects on Consumer Well-being [Time 1 and 2 Survey Summary Results]

While anecdotal evidence indicates financial advice affects consumers’ financial well-being, this research project is motivated by the absence of empirically-grounded research relating to the extent to which, and, importantly, how, financial planning advice contributes to broader client well-being. Accordingly, the aim of this project is to establish how the quality of financial planning advice can be optimised to add value, not only to clients’ financial situation, but also to broader aspects of their well-being. This broader construct of well-being captures a range of process and outcome factors that map to concepts of security, control, choice, mastery, and life satisfaction (Irving, 2012; Gallery, Gallery, Irving & Newton, 2011; Irving, Gallery, and Gallery, 2009). Financial planning is commonly purported to confer not only tangible benefits, but also intangible benefits, such as increased security and peace of mind that are considered as important, if not more important, than material outcomes. Such claims are intuitively appealing; however, little empirical evidence exists for the notion that engaging with a financial planner or adviser promotes peace of mind, feelings of security, and expands choices and possibilities. Nor is there evidence signalling what mechanisms might underpin such client benefits. In addressing this issue, we examine the financial planning advice (including financial product advice) provided to retail clients, and consider the short- and longer-term impacts on clients’ financial satisfaction and broader well-being. To this end, we examine both process (e.g., how financial planning advice is given) and outcome (e.g., financial situation) effects.

Failure to launch: The self-regulating Md -MYB10R6 gene from apple is active in flowers but not leaves of Petunia

Coloured foliage due to anthocyanin pigments (bronze/red/black) is an attractive trait that is often lacking in many bedding, ornamental and horticultural plants. Apples (Malus × domestica) containing an allelic variant of the anthocyanin regulator, Md-MYB10R6, are highly pigmented throughout the plant, due to autoregulation by MYB10 upon its own promoter. We investigated whether Md-MYB10R6 from apple is capable of functioning within the heterologous host Petunia hybrida to generate plants with novel pigmentation patterns. The Md-MYB10R6 transgene (MYB10–R6pro:MYB10:MYB10term) activated anthocyanin synthesis when transiently expressed in Antirrhinumroseadorsea petals and petunia leaf discs. Stable transgenic petunias containing Md-MYB10R6 lacked foliar pigmentation but had coloured flowers, complementing the an2 phenotype of ‘Mitchell’ petunia. The absence of foliar pigmentation was due to the failure of the Md-MYB10R6 gene to self-activate in vegetative tissues, suggesting that additional protein partners are required for Md-MYB10 to activate target genes in this heterologous system. In petunia flowers, where endogenous components including MYB-bHLH-WDR (MBW) proteins were present, expression of the Md-MYB10R6 promoter was initiated, allowing auto-regulation to occur and activating anthocyanin production. Md-MYB10 is capable of operating within the petunia MBW gene regulation network that controls the expression of the anthocyanin biosynthesis genes, AN1 (bHLH) and MYBx (R3-MYB repressor) in petals.

Effect of different surface profile on wear of rail steel (AS1085.1) used in Australian heavy-haul railways

The extreme diversity of conditions acting on railways necessitates a variety of experimental approaches to study the critical wear mechanisms that present themselves at the contact interface. This work investigates the effects of contact pressure and geometry in rolling-contact wear tests by using discs with different radii of curvature to simulate the varying contact conditions that may be typically found in the field. It is commonly adapted to line contact interface as it has constant contact pressure. But practical scenario of the rail wheel interface, the contact area increase and contact pressure change as tracks worn off. The tests were conducted without any significant amount of traction, but micro slip was still observed due to contact deformation. Moreover, variation of contact pressure was observed due to contact patch elongation and diameter reduction. Rolling contact fatigue, adhesive and sliding wear were observed on the curved contact interface. The development of different wear regimes and material removal phenomena were analysed using microscopic images in order to broaden the understanding of the wear mechanisms occurring in the rail-wheel contact.

Resistance exercise with low glycogen increases p53 phosphorylation and PGC-1α mRNA in skeletal muscle

Purpose We determined the effect of reduced muscle glycogen availability on cellular pathways regulating mitochondrial biogenesis and substrate utilization after a bout of resistance exercise. Methods Eight young, recreationally trained men undertook a glycogen depletion protocol of one-leg cycling to fatigue (LOW), while the contralateral (control) leg rested (CONT). Following an overnight fast, subjects completed 8 sets of 5 unilateral leg press repetitions (REX) at 80 % 1 Repetition Maximum (1RM) on each leg. Subjects consumed 500 mL protein/CHO beverage (20 g whey + 40 g maltodextrin) upon completion of REX and 2 h later. Muscle biopsies were obtained at rest and 1 and 4 h after REX in both legs. Results Resting muscle glycogen was higher in the CONT than LOW leg (~384 ± 114 vs 184 ± 36 mmol kg−1 dry wt; P < 0.05), and 1 h and 4 h post-exercise (P < 0.05). Phosphorylation of p53Ser15 increased 1 h post-exercise in LOW (~115 %, P < 0.05) and was higher than CONT at this time point (~87 %, P < 0.05). p38MAPKThr180/Tyr182 phosphorylation increased 1 h post-exercise in both CONT and LOW (~800–900 %; P < 0.05) but remained above rest at 4 h only in CONT (~585 %, P < 0.05; different between legs P < 0.05). Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) mRNA was elevated 4 h post-exercise in LOW (~200 %, P < 0.05; different between legs P < 0.05). There were no changes in Fibronectin type III domain-containing protein 5 (FNDC5) mRNA for CONT or LOW legs post-exercise. Conclusion Undertaking resistance exercise with low glycogen availability may enhance mitochondrial-related adaptations through p53 and PGC-1α-mediated signalling.