448 resultados para non conventional secretion


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Lipopolysaccharide-activated macrophages rapidly synthesize and secrete tumor necrosis factor α (TNFα) to prime the immune system. Surface delivery of membrane carrying newly synthesized TNFα is controlled and limited by the level of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 4 and SNAP-23. Many functions in immune cells are coordinated from lipid rafts in the plasmamembrane, and we investigated a possible role for lipid rafts in TNFα trafficking and secretion. TNFα surface delivery and secretion were found to be cholesterol- dependent. Upon macrophage activation, syntaxin 4 was recruited to cholesterol-dependent lipid rafts, whereas its regulatory protein, Munc18c, was excluded from the rafts. Syntaxin 4 in activated macrophages localized to discrete cholesterol-dependent puncta on the plasmamembrane, particularly on filopodia. Imaging the early stages of TNFα surface distribution revealed these puncta to be the initial points of TNFα delivery. During the early stages of phagocytosis, syntaxin 4 was recruited to the phagocytic cup in a cholesterol dependent manner. Insertion of VAMP3-positive recycling endosome membrane is required for efficient ingestion of a pathogen. Without this recruitment of syntaxin 4, it is not incorporated into the plasma membrane, and phagocytosis is greatly reduced. Thus, relocation of syntaxin 4 into lipid rafts in macrophages is a critical and rate-limiting step in initiating an effective immune response.

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Membrane traffic in activated macrophages is required for two critical events in innate immunity: proinflammatory cytokine secretion and phagocytosis of pathogens. We found a joint trafficking pathway linking both actions, which may economize membrane transport and augment the immune response. Tumor necrosis factor α (TNFα) is trafficked from the Golgi to the recycling endosome (RE), where vesicle-associated membrane protein 3 mediates its delivery to the cell surface at the site of phagocytic cup formation. Fusion of the RE at the cup simultaneously allows rapid release of TNFα and expands the membrane for phagocytosis.

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This paper illustrates robust fixed order power oscillation damper design for mitigating power systems oscillations. From implementation and tuning point of view, such low and fixed structure is common practice for most practical applications, including power systems. However, conventional techniques of optimal and robust control theory cannot handle the constraint of fixed-order as it is, in general, impossible to ensure a target closed-loop transfer function by a controller of any given order. This paper deals with the problem of synthesizing or designing a feedback controller of dynamic order for a linear time-invariant plant for a fixed plant, as well as for an uncertain family of plants containing parameter uncertainty, so that stability, robust stability and robust performance are attained. The desired closed-loop specifications considered here are given in terms of a target performance vector representing a desired closed-loop design. The performance of the designed controller is validated through non-linear simulations for a range of contingencies.

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Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates TLR signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii depleted conditioned media leads to enhanced macrophage activation and increased TNF secretion compared to cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.

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This paper presents a feasible spatial collision avoidance approach for fixed-wing unmanned aerial vehicles (UAVs). The proposed strategy aims to achieve the desired relative bearing in the horizontal plane and relative elevation in the vertical plane so that the host aircraft is able to avoid collision with the intruder aircraft in 3D. The host aircraft will follow a desired trajectory in the collision avoidance course and resume the pre-arranged trajectory after collision is avoided. The approaching stopping condition is determined for the host aircraft to trigger an evasion maneuver to avoid collision in terms of measured heading. A switching controller is designed to achieve the spatial collision avoidance strategy. Simulation results demonstrate that the proposed approach can effectively avoid spatial collision, making it suitable for integration into flight control systems of UAVs.

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Conventional training methods for nurses involve many physical factors that place limits on potential class sizes. Alternate training methods with lower physical requirements may support larger class sizes, but given the tactile quality of nurse training, are most appropriately applied to supplement the conventional methods. However, where the importance of physical factors are periphery, such alternate training methods can provide an important way to increase upper class-size limits and therefore the rate of trained nurses entering the important role of critical care. A major issue in ICU training is that the trainee can be released into a real-life intensive care scenario with sub optimal preparation and therefore a level of anxiety for the student concerned, and some risk for the management level nurses, as patient safety is paramount. This lack of preparation places a strain on the allocation of human and non-human resources to teaching, as students require greater levels of supervision. Such issues are a concern to ICU management, as they relate to nursing skill development and patient health outcomes, as nursing training is potentially dangerous for patients who are placed in the care of inexperienced staff. As a solution to this problem, we present a prototype ICU handover training environment that has been developed in a socially interactive virtual world. Nurses in training can connect remotely via the Internet to this environment and engage in collaborative ICU handover training classes.

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Directors’ and executives’ remuneration, including levels of pay, accountability and transparency, is controversial. Section 250R of the CLERP (Audit Reform & Disclosure) Act 2004 that was not greatly anticipated, requires the holding of a non-binding resolution on board remuneration at companies’ annual general meetings. The reform has been criticised on the basis that, inter alia, it blurs the respective roles of shareholders and directors. This article identifies possible motivations for the imposition of the non-binding resolution in Australia. These are evaluated with reference to sources of corporate governance policy and the current state of Australia’s relevant corporate governance structures. We speculate that the non-binding vote will not amount to a substantive addition to the corporate governance regime.

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Charge of the light brigade: A molecule is able to walk back and forth upon a five-foothold pentaethylenimine track without external intervention. The 1D random walk is highly processive (mean step number 530) and exchange takes place between adjacent amine groups in a stepwise fashion. The walker performs a simple task whilst walking: quenching of the fluorescence of an anthracene group sited at one end of the track. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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There are several popular soil moisture measurement methods today such as time domain reflectometry, electromagnetic (EM) wave, electrical and acoustic methods. Significant studies have been dedicated in developing method of measurements using those concepts, especially to achieve the characteristics of noninvasiveness. EM wave method provides an advantage because it is non-invasive to the soil and does not need to utilise probes to penetrate or bury in the soil. But some EM methods are also too complex, expensive, and not portable for the application of Wireless Sensor Networks; for example satellites or UAV (Unmanned Aerial Vehicle) based sensors. This research proposes a method in detecting changes in soil moisture using soil-reflected electromagnetic (SREM) wave from Wireless Sensor Networks (WSNs). Studies have shown that different levels of soil moisture will affects soil’s dielectric properties, such as relative permittivity and conductivity, and in turns change its reflection coefficients. The SREM wave method uses a transmitter adjacent to a WSNs node with purpose exclusively to transmit wireless signals that will be reflected by the soil. The strength from the reflected signal that is determined by the soil’s reflection coefficients is used to differentiate the level of soil moisture. The novel nature of this method comes from using WSNs communication signals to perform soil moisture estimation without the need of external sensors or invasive equipment. This innovative method is non-invasive, low cost and simple to set up. There are three locations at Brisbane, Australia chosen as the experiment’s location. The soil type in these locations contains 10–20% clay according to the Australian Soil Resource Information System. Six approximate levels of soil moisture (8, 10, 13, 15, 18 and 20%) are measured at each location; with each measurement consisting of 200 data. In total 3600 measurements are completed in this research, which is sufficient to achieve the research objective, assessing and proving the concept of SREM wave method. These results are compared with reference data from similar soil type to prove the concept. A fourth degree polynomial analysis is used to generate an equation to estimate soil moisture from received signal strength as recorded by using the SREM wave method.

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Percolation flow problems are discussed in many research fields, such as seepage hydraulics, groundwater hydraulics, groundwater dynamics and fluid dynamics in porous media. Many physical processes appear to exhibit fractional-order behavior that may vary with time, or space, or space and time. The theory of pseudodifferential operators and equations has been used to deal with this situation. In this paper we use a fractional Darcys law with variable order Riemann-Liouville fractional derivatives, this leads to a new variable-order fractional percolation equation. In this paper, a new two-dimensional variable-order fractional percolation equation is considered. A new implicit numerical method and an alternating direct method for the two-dimensional variable-order fractional model is proposed. Consistency, stability and convergence of the implicit finite difference method are established. Finally, some numerical examples are given. The numerical results demonstrate the effectiveness of the methods. This technique can be used to simulate a three-dimensional variable-order fractional percolation equation.

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In the current era of global economic instability, business and industry have already identified a widening gap between graduate skills and employability. An important element of this is the lack of entrepreneurial skills in graduates. This Teaching Fellowship investigated two sides of a story about entrepreneurial skills and their teaching. Senior players in the innovation commercialisation industry, a high profile entrepreneurial sector, were surveyed to gauge their needs and experiences of graduates they employ. International contexts of entrepreneurship education were investigated to explore how their teaching programs impart the skills of entrepreneurship. Such knowledge is an essential for the design of education programs that can deliver the entrepreneurial skills deemed important by industry for future sustainability. Two programs of entrepreneurship education are being implemented at QUT that draw on the best practice exemplars investigated during this Fellowship. The QUT Innovation Space (QIS) focuses on capturing the innovation and creativity of students, staff and others. The QIS is a physical and virtual meeting and networking space; a connected community enhancing the engagement of participants. The Q_Hatchery is still embryonic; but it is intended to be an innovation community that brings together nascent entrepreneurial businesses to collaborate, train and support each other. There is a niche between concept product and business incubator where an experiential learning environment for otherwise isolated ‘garage-at-home’ businesses could improve success rates. The QIS and the Q_Hatchery serve as living research laboratories to trial the concepts emerging from the skills survey. The survey of skills requirements of the innovation commercialisation industry has produced a large and high quality data set still being explored. Work experience as an employability factor has already emerged as an industry requirement that provides employee maturity. Exploratory factor analysis of the skills topics surveyed has led to a process-based conceptual model for teaching and learning higher-order entrepreneurial skills. Two foundational skills domains (Knowledge, Awareness) are proposed as prerequisites which allow individuals with a suite of early stage entrepreneurial and behavioural skills (Pre-leadership) to further leverage their careers into a leadership role in industry with development of skills around higher order elements of entrepreneurship, management in new business ventures and progressing winning technologies to market. The next stage of the analysis is to test the proposed model through structured equation modelling. Another factor that emerged quickly from the survey analysis broadens the generic concept of team skills currently voiced in Australian policy documents discussing the employability agenda. While there was recognition of the role of sharing, creating and using knowledge in a team-based interdisciplinary context, the adoption and adaptation of behaviours and attitudes of other team members of different disciplinary backgrounds (interprofessionalism) featured as an issue. Most undergraduates are taught and undertake teamwork in silos and, thus, seldom experience a true real-world interdisciplinary environment. Enhancing the entrepreneurial capacity of Australian industry is essential for the economic health of the country and can only be achieved by addressing the lack of entrepreneurial skills in graduates from the higher education system. This Fellowship has attempted to address this deficiency by identifying the skills requirements and providing frameworks for their teaching.

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In TSPD Pty Ltd v Resortrez Pty Ltd [2008] QSC 001 Fryberg J made an order permitting the applicant to inspect and copy documents which had been produced to the court under a subpoena, but had remained in the registry. Though not essential to the decision the judgment contains some interesting discussion about the construction of r 242 of the Uniform Civil Procedure Rules 1999 (Qld) (UCPR).

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Objective The aim of this study was to demonstrate the potential of near-infrared (NIR) spectroscopy for categorizing cartilage degeneration induced in animal models. Method Three models of osteoarthritic degeneration were induced in laboratory rats via one of the following methods: (i) menisectomy (MSX); (ii) anterior cruciate ligament transaction (ACLT); and (iii) intra-articular injection of mono-ido-acetete (1 mg) (MIA), in the right knee joint, with 12 rats per model group. After 8 weeks, the animals were sacrificed and tibial knee joints were collected. A custom-made nearinfrared (NIR) probe of diameter 5 mm was placed on the cartilage surface and spectral data were acquired from each specimen in the wavenumber range 4 000 – 12 500 cm−1. Following spectral data acquisition, the specimens were fixed and Safranin–O staining was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis based on principal component analysis and partial least squares regression, the spectral data were then related to the Mankinscores of the samples tested. Results Mild to severe degenerative cartilage changes were observed in the subject animals. The ACLT models showed mild cartilage degeneration, MSX models moderate, and MIA severe cartilage degenerative changes both morphologically and histologically. Our result demonstrate that NIR spectroscopic information is capable of separating the cartilage samples into different groups relative to the severity of degeneration, with NIR correlating significantly with their Mankinscore (R2 = 88.85%). Conclusion We conclude that NIR is a viable tool for evaluating articularcartilage health and physical properties such as change in thickness with degeneration.

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Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life.