385 resultados para PP-MA
Resumo:
Tyrosine trans-phosphorylation is a key event in receptor tyrosine kinase signaling, yet, the structural basis for this process has eluded definition. Here, we present the crystal structure of the FGF receptor 2 kinases caught in the act of trans-phosphorylation of Y769, the major C-terminal phosphorylation site. The structure reveals that enzyme- and substrate-acting kinases engage each other through elaborate and specific interactions not only in the immediate vicinity of Y769 and the enzyme active site, but also in regions that are as much of 18 A away from D626, the catalytic base in the enzyme active site. These interactions lead to an unprecedented level of specificity and precision during the trans-phosphorylation on Y769. Time-resolved mass spectrometry analysis supports the observed mechanism of trans-phosphorylation. Our data provide a molecular framework for understanding the mechanism of action of Kallmann syndrome mutations and the order of trans-phosphorylation reactions in FGFRs. We propose that the salient mechanistic features of Y769 trans-phosphorylation are applicable to trans-phosphorylation of the equivalent major phosphorylation sites in many other RTKs.
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We report that 10% of melanoma tumors and cell lines harbor mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. These novel mutations include three truncating mutations and 20 missense mutations occurring at evolutionary conserved residues in FGFR2 as well as among all four FGFRs. The mutation spectrum is characteristic of those induced by UV radiation. Mapping of these mutations onto the known crystal structures of FGFR2 followed by in vitro and in vivo studies show that these mutations result in receptor loss of function through several distinct mechanisms, including loss of ligand binding affinity, impaired receptor dimerization, destabilization of the extracellular domains, and reduced kinase activity. To our knowledge, this is the first demonstration of loss-of-function mutations in a class IV receptor tyrosine kinase in cancer. Taken into account with our recent discovery of activating FGFR2 mutations in endometrial cancer, we suggest that FGFR2 may join the list of genes that play context-dependent opposing roles in cancer.
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This work details the results of a face authentication test (FAT2004) (http://www.ee.surrey.ac.uk/banca/icpr2004) held in conjunction with the 17th International Conference on Pattern Recognition. The contest was held on the publicly available BANCA database (http://www.ee.surrey.ac.uk/banca) according to a defined protocol (E. Bailly-Bailliere et al., June 2003). The competition also had a sequestered part in which institutions had to submit their algorithms for independent testing. 13 different verification algorithms from 10 institutions submitted results. Also, a standard set of face recognition software packages from the Internet (http://www.cs.colostate.edu/evalfacerec) were used to provide a baseline performance measure.
Resumo:
The aim of this research is to explore the meaning of the experience of school-based youth health nursing in Queensland, Australia. The research follows a qualitative approach and is based on indepth interviews. The dominant experience is negative because participants feel they have to battle to gain respect and survive in the school environment. The small, positive experience of school-based youth health nursing is related to student consultations. Student consultations are a ‘golden egg’ because participants gain a sense of reward from making a difference to student wellbeing. This paper proposes operational recommendations including those related to health promotion and professional development and strategic recommendations regarding this model of school nursing. The authors conclude, first, that this ‘golden egg’ should be promoted to ensure all school nurses reap the rewards, second, that this model of school nursing is not the most effective model.
Resumo:
Continuing monitoring of diesel engine performance is critical for early detection of fault developments in the engine before they materialize and become a functional failure. Instantaneous crank angular speed (IAS) analysis is one of a few non intrusive condition monitoring techniques that can be utilized for such tasks. In this experimental study, IAS analysis was employed to estimate the loading condition of a 4-stroke 4-cylinder diesel engine in a laboratory condition. It was shown that IAS analysis can provide useful information about engine speed variation caused by the changing piston momentum and crankshaft acceleration during the engine combustion process. It was also found that the major order component of the IAS spectrum directly associated with the engine firing frequency (at twice the mean shaft revolution speed) can be utilized to estimate the engine loading condition regardless of whether the engine is operating at normal running conditions or in a simulated faulty injector case. The amplitude of this order component follows a clear exponential curve as the loading condition changes. A mathematical relationship was established for the estimation of the engine power output based on the amplitude of the major order component of the measured IAS spectrum.
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In this work, we present the development of a Pt/graphene/SiC device for hydrogen gas sensing. A single layer of graphene was deposited on 6H-SiC via chemical vapor deposition. The presence of graphene C-C bonds was observed via X-ray photoelectron spectroscopy analysis. Current-voltage characteristics of the device were measured at the presence of hydrogen at different temperatures, from 25°C to 170°C. The dynamic response of the device was recorded towards hydrogen gas at an optimum temperature of 130°C. A voltage shift of 191 mV was recorded towards 1% hydrogen at −1 mA constant current.
Resumo:
Non-invasive vibration analysis has been used extensively to monitor the progression of dental implant healing and stabilization. It is now being considered as a method to monitor femoral implants in transfemoral amputees. This paper evaluates two modal analysis excitation methods and investigates their capabilities in detecting changes at the interface between the implant and the bone that occur during osseointegration. Excitation of bone-implant physical models with the electromagnetic shaker provided higher coherence values and a greater number of modes over the same frequency range when compared to the impact hammer. Differences were detected in the natural frequencies and fundamental mode shape of the model when the fit of the implant was altered in the bone. The ability to detect changes in the model dynamic properties demonstrates the potential of modal analysis in this application and warrants further investigation.
Resumo:
Providing effective IT support for business processes has become crucial for enterprises to stay competitive. In response to this need numerous process support paradigms (e.g., workflow management, service flow management, case handling), process specification standards (e.g., WS-BPEL, BPML, BPMN), process tools (e.g., ARIS Toolset, Tibco Staffware, FLOWer), and supporting methods have emerged in recent years. Summarized under the term “Business Process Management” (BPM), these paradigms, standards, tools, and methods have become a success-critical instrument for improving process performance.
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We propose an approach to employ eigen light-fields for face recognition across pose on video. Faces of a subject are collected from video frames and combined based on the pose to obtain a set of probe light-fields. These probe data are then projected to the principal subspace of the eigen light-fields within which the classification takes place. We modify the original light-field projection and found that it is more robust in the proposed system. Evaluation on VidTIMIT dataset has demonstrated that the eigen light-fields method is able to take advantage of multiple observations contained in the video.
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The design of artificial intelligence in computer games is an important component of a player's game play experience. As games are becoming more life-like and interactive, the need for more realistic game AI will increase. This is particularly the case with respect to AI that simulates how human players act, behave and make decisions. The purpose of this research is to establish a model of player-like behavior that may be effectively used to inform the design of artificial intelligence to more accurately mimic a player's decision making process. The research uses a qualitative analysis of player opinions and reactions while playing a first person shooter video game, with recordings of their in game actions, speech and facial characteristics. The initial studies provide player data that has been used to design a model of how a player behaves.
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For people with intellectual disabilities there are significant barriers to inclusion in socially cooperative endeavours. This paper investigates the effectiveness of Stomp, a tangible user interface (TUI) designed to provide new participatory experiences for people with intellectual disability. Results from an observational study reveal the extent to which the Stomp system supports social and physical interaction. The tangible, spatial and embodied qualities of Stomp result in an experience that does not rely on the acquisition of specific competencies before interaction and engagement can occur.
Resumo:
Backgrounds Whether suicide in China has significant seasonal variations is unclear. The aim of this study is to examine the seasonality of suicide in Shandong China and to assess the associations of suicide seasonality with gender, residence, age and methods of suicide. Methods Three types of tests (Chi-square, Edwards' T and Roger's Log method) were used to detect the seasonality of the suicide data extracted from the official mortality data of Shandong Disease Surveillance Point (DSP) system. Peak/low ratios (PLRs) and 95% confidence intervals (CIs) were calculated to indicate the magnitude of seasonality. Results A statistically significant seasonality with a single peak in suicide rates in spring and early summer, and a dip in winter was observed, which remained relatively consistent over years. Regardless of gender, suicide seasonality was more pronounced in rural areas, younger age groups and for non-violent methods, in particular, self-poisoning by pesticide. Conclusions There are statistically significant seasonal variations of completed suicide for both men and women in Shandong, China. Differences exist between residence (urban/rural), age groups and suicide methods. Results appear to support a sociological explanation of suicide seasonality.
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The existing Collaborative Filtering (CF) technique that has been widely applied by e-commerce sites requires a large amount of ratings data to make meaningful recommendations. It is not directly applicable for recommending products that are not frequently purchased by users, such as cars and houses, as it is difficult to collect rating data for such products from the users. Many of the e-commerce sites for infrequently purchased products are still using basic search-based techniques whereby the products that match with the attributes given in the target user's query are retrieved and recommended to the user. However, search-based recommenders cannot provide personalized recommendations. For different users, the recommendations will be the same if they provide the same query regardless of any difference in their online navigation behaviour. This paper proposes to integrate collaborative filtering and search-based techniques to provide personalized recommendations for infrequently purchased products. Two different techniques are proposed, namely CFRRobin and CFAg Query. Instead of using the target user's query to search for products as normal search based systems do, the CFRRobin technique uses the products in which the target user's neighbours have shown interest as queries to retrieve relevant products, and then recommends to the target user a list of products by merging and ranking the returned products using the Round Robin method. The CFAg Query technique uses the products that the user's neighbours have shown interest in to derive an aggregated query, which is then used to retrieve products to recommend to the target user. Experiments conducted on a real e-commerce dataset show that both the proposed techniques CFRRobin and CFAg Query perform better than the standard Collaborative Filtering (CF) and the Basic Search (BS) approaches, which are widely applied by the current e-commerce applications. The CFRRobin and CFAg Query approaches also outperform the e- isting query expansion (QE) technique that was proposed for recommending infrequently purchased products.
Resumo:
A novel m-ary tree based approach is presented to solve asset management decisions which are combinatorial in nature. The approach introduces a new dynamic constraint based control mechanism which is capable of excluding infeasible solutions from the solution space. The approach also provides a solution to the challenges with ordering of assets decisions.