998 resultados para Receptor sensor de cálcio


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Railway signaling facilitates two main functions, namely, train detection and train control, in order to maintain safe separations among the trains. Track circuits are the most commonly used train detection means with the simple open/close circuit principles; and subsequent adoption of axle counters further allows the detection of trains under adverse track conditions. However, with electrification and power electronics traction drive systems, aggravated by the electromagnetic interference in the vicinity of the signaling system, railway engineers often find unstable or even faulty operations of track circuits and axle counting systems, which inevitably jeopardizes the safe operation of trains. A new means of train detection, which is completely free from electromagnetic interference, is therefore required for the modern railway signaling system. This paper presents a novel optical fiber sensor signaling system. The sensor operation, field setup, axle detection solution set, and test results of an installation in a trial system on a busy suburban railway line are given.

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Wireless Multi-media Sensor Networks (WMSNs) have become increasingly popular in recent years, driven in part by the increasing commoditization of small, low-cost CMOS sensors. As such, the challenge of automatically calibrating these types of cameras nodes has become an important research problem, especially for the case when a large quantity of these type of devices are deployed. This paper presents a method for automatically calibrating a wireless camera node with the ability to rotate around one axis. The method involves capturing images as the camera is rotated and computing the homographies between the images. The camera parameters, including focal length, principal point and the angle and axis of rotation can then recovered from two or more homographies. The homography computation algorithm is designed to deal with the limited resources of the wireless sensor and to minimize energy con- sumption. In this paper, a modified RANdom SAmple Consensus (RANSAC) algorithm is proposed to effectively increase the efficiency and reliability of the calibration procedure.

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The multi-criteria decision making methods, Preference METHods for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA), and the two-way Positive Matrix Factorization (PMF) receptor model were applied to airborne fine particle compositional data collected at three sites in Hong Kong during two monitoring campaigns held from November 2000 to October 2001 and November 2004 to October 2005. PROMETHEE/GAIA indicated that the three sites were worse during the later monitoring campaign, and that the order of the air quality at the sites during each campaign was: rural site > urban site > roadside site. The PMF analysis on the other hand, identified 6 common sources at all of the sites (diesel vehicle, fresh sea salt, secondary sulphate, soil, aged sea salt and oil combustion) which accounted for approximately 68.8 ± 8.7% of the fine particle mass at the sites. In addition, road dust, gasoline vehicle, biomass burning, secondary nitrate, and metal processing were identified at some of the sites. Secondary sulphate was found to be the highest contributor to the fine particle mass at the rural and urban sites with vehicle emission as a high contributor to the roadside site. The PMF results are broadly similar to those obtained in a previous analysis by PCA/APCS. However, the PMF analysis resolved more factors at each site than the PCA/APCS. In addition, the study demonstrated that combined results from multi-criteria decision making analysis and receptor modelling can provide more detailed information that can be used to formulate the scientific basis for mitigating air pollution in the region.

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Prostate cancer is the second most common cause of cancer-related deaths in Western males. Current diagnostic, prognostic and treatment approaches are not ideal and advanced metastatic prostate cancer is incurable. There is an urgent need for improved adjunctive therapies and markers for this disease. GPCRs are likely to play a significant role in the initiation and progression of prostate cancer. Over the last decade, it has emerged that G protein coupled receptors (GPCRs) are likely to function as homodimers and heterodimers. Heterodimerisation between GPCRs can result in the formation of novel pharmacological receptors with altered functional outcomes, and a number of GPCR heterodimers have been implicated in the pathogenesis of human disease. Importantly, novel GPCR heterodimers represent potential new targets for the development of more specific therapeutic drugs. Ghrelin is a 28 amino acid peptide hormone which has a unique n-octanoic acid post-translational modification. Ghrelin has a number of important physiological roles, including roles in appetite regulation and the stimulation of growth hormone release. The ghrelin receptor is the growth hormone secretagogue receptor type 1a, GHS-R1a, a seven transmembrane domain GPCR, and GHS-R1b is a C-terminally truncated isoform of the ghrelin receptor, consisting of five transmembrane domains. Growing evidence suggests that ghrelin and the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, may have a role in the progression of a number of cancers, including prostate cancer. Previous studies by our research group have shown that the truncated ghrelin receptor isoform, GHS-R1b, is not expressed in normal prostate, however, it is expressed in prostate cancer. The altered expression of this truncated isoform may reflect a difference between a normal and cancerous state. A number of mutant GPCRs have been shown to regulate the function of their corresponding wild-type receptors. Therefore, we investigated the potential role of interactions between GHS-R1a and GHS-R1b, which are co-expressed in prostate cancer and aimed to investigate the function of this potentially new pharmacological receptor. In 2005, obestatin, a 23 amino acid C-terminally amidated peptide derived from preproghrelin was identified and was described as opposing the stimulating effects of ghrelin on appetite and food intake. GPR39, an orphan GPCR which is closely related to the ghrelin receptor, was identified as the endogenous receptor for obestatin. Recently, however, the ability of obestatin to oppose the effects of ghrelin on appetite and food intake has been questioned, and furthermore, it appears that GPR39 may in fact not be the obestatin receptor. The role of GPR39 in the prostate is of interest, however, as it is a zinc receptor. Zinc has a unique role in the biology of the prostate, where it is normally accumulated at high levels, and zinc accumulation is altered in the development of prostate malignancy. Ghrelin and zinc have important roles in prostate cancer and dimerisation of their receptors may have novel roles in malignant prostate cells. The aim of the current study, therefore, was to demonstrate the formation of GHS-R1a/GHS-R1b and GHS-R1a/GPR39 heterodimers and to investigate potential functions of these heterodimers in prostate cancer cell lines. To demonstrate dimerisation we first employed a classical co-immunoprecipitation technique. Using cells co-overexpressing FLAG- and Myc- tagged GHS-R1a, GHS-R1b and GPR39, we were able to co-immunoprecipitate these receptors. Significantly, however, the receptors formed high molecular weight aggregates. A number of questions have been raised over the propensity of GPCRs to aggregate during co-immunoprecipitation as a result of their hydrophobic nature and this may be misinterpreted as receptor dimerisation. As we observed significant receptor aggregation in this study, we used additional methods to confirm the specificity of these putative GPCR interactions. We used two different resonance energy transfer (RET) methods; bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), to investigate interactions between the ghrelin receptor isoforms and GPR39. RET is the transfer of energy from a donor fluorophore to an acceptor fluorophore when they are in close proximity, and RET methods are, therefore, applicable to the observation of specific protein-protein interactions. Extensive studies using the second generation bioluminescence resonance energy transfer (BRET2) technology were performed, however, a number of technical limitations were observed. The substrate used during BRET2 studies, coelenterazine 400a, has a low quantum yield and rapid signal decay. This study highlighted the requirement for the expression of donor and acceptor tagged receptors at high levels so that a BRET ratio can be determined. After performing a number of BRET2 experimental controls, our BRET2 data did not fit the predicted results for a specific interaction between these receptors. The interactions that we observed may in fact represent ‘bystander BRET’ resulting from high levels of expression, forcing the donor and acceptor into close proximity. Our FRET studies employed two different FRET techniques, acceptor photobleaching FRET and sensitised emission FRET measured by flow cytometry. We were unable to observe any significant FRET, or FRET values that were likely to result from specific receptor dimerisation between GHS-R1a, GHS-R1b and GPR39. While we were unable to conclusively demonstrate direct dimerisation between GHS-R1a, GHS-R1b and GPR39 using several methods, our findings do not exclude the possibility that these receptors interact. We aimed to investigate if co-expression of combinations of these receptors had functional effects in prostate cancers cells. It has previously been demonstrated that ghrelin stimulates cell proliferation in prostate cancer cell lines, through ERK1/2 activation, and GPR39 can stimulate ERK1/2 signalling in response to zinc treatments. Additionally, both GHS-R1a and GPR39 display a high level of constitutive signalling and these constitutively active receptors can attenuate apoptosis when overexpressed individually in some cell types. We, therefore, investigated ERK1/2 and AKT signalling and cell survival in prostate cancer the potential modulation of these functions by dimerisation between GHS-R1a, GHS-R1b and GPR39. Expression of these receptors in the PC-3 prostate cancer cell line, either alone or in combination, did not alter constitutive ERK1/2 or AKT signalling, basal apoptosis or tunicamycin-stimulated apoptosis, compared to controls. In summary, the potential interactions between the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, and the related zinc receptor, GPR39, and the potential for functional outcomes in prostate cancer were investigated using a number of independent methods. We did not definitively demonstrate the formation of these dimers using a number of state of the art methods to directly demonstrate receptor-receptor interactions. We investigated a number of potential functions of GPR39 and GHS-R1a in the prostate and did not observe altered function in response to co-expression of these receptors. The technical questions raised by this study highlight the requirement for the application of extensive controls when using current methods for the demonstration of GPCR dimerisation. Similar findings in this field reflect the current controversy surrounding the investigation of GPCR dimerisation. Although GHS-R1a/GHS-R1b or GHS-R1a/GPR39 heterodimerisation was not clearly demonstrated, this study provides a basis for future investigations of these receptors in prostate cancer. Additionally, the results presented in this study and growing evidence in the literature highlight the requirement for an extensive understanding of the experimental method and the performance of a range of controls to avoid the spurious interpretation of data gained from artificial expression systems. The future development of more robust techniques for investigating GPCR dimerisation is clearly required and will enable us to elucidate whether GHS-R1a, GHS-R1b and GPR39 form physiologically relevant dimers.

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Heart failure is a complex disorder, characterized by activation of the sympathetic nervous system, leading to dysregulated Ca2+ homeostasis in cardiac myocytes and tissue remodeling. In a variety of diseases, cardiac malfunction is associated with aberrant fluxes of Ca2+ across both the surface membrane and the internal Ca2+ store, the sarcoplasmic reticulum (SR). One prominent hypothesis residues is that in heart failure, the activity of the ryanodine receptor (RyR2) Ca2+ release channel in the SR is increased due to excess phosphorylation and that this contributes to excess SR Ca2+ leak in diastole, reduced SR Ca2+ load and decreased contractility (Huke & Bers, 2008). There is controversy over which serine residues in RyR2 are hyperphosphorylated in animal models of heart failure and whether this is via the CaMKII or the PKA-linked signaling pathway. S2808, S2814 and S2030 in RyR2 have been variously claimed to be hyperphosphorylated. Our aim was to examine the degree of phosphorylation of these residues in RyR2 from failing human hearts. The use of human tissue was approved by the Human Research Ethics Committee, The Prince Charles Hospital, EC28114. Left ventricular tissue samples were obtained from an explanted heart of a patient with endstage heart failure (Emery Dreifuss Muscular Dystrophy with cardiomyopathy) and non-failing tissue was from a patient with cystic fibrosis undergoing heart-lung transplantation with no history of heart disease. SR vesicles were prepared as described by Laver et al. (1995) and examined with SDS-Page and Western Blot. Transferred proteins were probed with antibodies to detect total protein phosphorylation, phosphorylation of RyR2 serine residues S2808, S2814, S2030 and for the key proteins calsequestrin, triadin, junctin and FKBP12.6. To avoid membrane stripping artifact, each membrane was exposed to one phosphorylation-specific antibody and signal densities quantified using Bio-Rad Quantity One software. We found no distinguishable difference between failing and healthy hearts in the protein expression levels of RyR2, triadin, junctin or calsequestrin. We found an expected upregulation of total RyR2 phosphorylation in the failing heart sample, compared to a matched amount of RyR2 (quantified using densiometry) in healthy heart. Probing with antibodies detecting only the phosphorylated form of the specific RyR2 residues showed that the increase in total RyR2 phosphorylation in the failing heart was due to hyperphosphorylation of S2808 and S2814. We found that S2030 phosphorylation levels were unchanged in human heart failure. Interestingly, we found that S2030 has a basal level of phosphorylation in the healthy human heart, different from the absence of basal phosphorylation recently reported in rodent heart (Huke & Bers, 2008). Finally, preliminary results indicate that less FKBP 12.6 is associated with RyR2 in the failing heart, possibly as a consequence of PKA activation. In conclusion, residues S2808 and S2814 are hyperphosphorylated in human heart failure, presumably due to upregulation of the CaMKII and/or PKA signaling pathway as a result of chronic activation of the sympathetic nervous system. Such changes in RyR2 phosphorylation are believed to contribute to the leaky RyR2 phenotype associated with heart failure, which increases the incidence of arrhythmia and contributes to the severely impaired contractile performance of the failing heart. Huke S & Bers DM. (2008). Ryanodine receptor phosphorylation at serine 2030, 2808 and 2814 in rat cardiomyocytes. Biochemical and Biophysical Research Communications 376, 80-85. Laver DR, Roden LD, Ahern GP, Eager KR, Junankar PR & Dulhunty AF. (1995). Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle. Journal of Membrane Biology 147, 7-22. Proceedings

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Harmful Algal Blooms (HABs) have become an important environmental concern along the western coast of the United States. Toxic and noxious blooms adversely impact the economies of coastal communities in the region, pose risks to human health, and cause mortality events that have resulted in the deaths of thousands of fish, marine mammals and seabirds. One goal of field-based research efforts on this topic is the development of predictive models of HABs that would enable rapid response, mitigation and ultimately prevention of these events. In turn, these objectives are predicated on understanding the environmental conditions that stimulate these transient phenomena. An embedded sensor network (Fig. 1), under development in the San Pedro Shelf region off the Southern California coast, is providing tools for acquiring chemical, physical and biological data at high temporal and spatial resolution to help document the emergence and persistence of HAB events, supporting the design and testing of predictive models, and providing contextual information for experimental studies designed to reveal the environmental conditions promoting HABs. The sensor platforms contained within this network include pier-based sensor arrays, ocean moorings, HF radar stations, along with mobile sensor nodes in the form of surface and subsurface autonomous vehicles. FreewaveTM radio modems facilitate network communication and form a minimally-intrusive, wireless communication infrastructure throughout the Southern California coastal region, allowing rapid and cost-effective data transfer. An emerging focus of this project is the incorporation of a predictive ocean model that assimilates near-real time, in situ data from deployed Autonomous Underwater Vehicles (AUVs). The model then assimilates the data to increase the skill of both nowcasts and forecasts, thus providing insight into bloom initiation as well as the movement of blooms or other oceanic features of interest (e.g., thermoclines, fronts, river discharge, etc.). From these predictions, deployed mobile sensors can be tasked to track a designated feature. This focus has led to the creation of a technology chain in which algorithms are being implemented for the innovative trajectory design for AUVs. Such intelligent mission planning is required to maneuver a vehicle to precise depths and locations that are the sites of active blooms, or physical/chemical features that might be sources of bloom initiation or persistence. The embedded network yields high-resolution, temporal and spatial measurements of pertinent environmental parameters and resulting biology (see Fig. 1). Supplementing this with ocean current information and remotely sensed imagery and meteorological data, we obtain a comprehensive foundation for developing a fundamental understanding of HAB events. This then directs labor- intensive and costly sampling efforts and analyses. Additionally, we provide coastal municipalities, managers and state agencies with detailed information to aid their efforts in providing responsible environmental stewardship of their coastal waters.

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Autonomous Underwater Vehicles (AUVs) are revolutionizing oceanography through their versatility, autonomy and endurance. However, they are still an underutilized technology. For coastal operations, the ability to track a certain feature is of interest to ocean scientists. Adaptive and predictive path planning requires frequent communication with significant data transfer. Currently, most AUVs rely on satellite phones as their primary communication. This communication protocol is expensive and slow. To reduce communication costs and provide adequate data transfer rates, we present a hardware modification along with a software system that provides an alternative robust disruption- tolerant communications framework enabling cost-effective glider operation in coastal regions. The framework is specifically designed to address multi-sensor deployments. We provide a system overview and present testing and coverage data for the network. Additionally, we include an application of ocean-model driven trajectory design, which can benefit from the use of this network and communication system. Simulation and implementation results are presented for single and multiple vehicle deployments. The presented combination of infrastructure, software development and deployment experience brings us closer to the goal of providing a reliable and cost-effective data transfer framework to enable real-time, optimal trajectory design, based on ocean model predictions, to gather in situ measurements of interesting and evolving ocean features and phenomena.

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Mobile sensor platforms such as Autonomous Underwater Vehicles (AUVs) and robotic surface vessels, combined with static moored sensors compose a diverse sensor network that is able to provide macroscopic environmental analysis tool for ocean researchers. Working as a cohesive networked unit, the static buoys are always online, and provide insight as to the time and locations where a federated, mobile robot team should be deployed to effectively perform large scale spatiotemporal sampling on demand. Such a system can provide pertinent in situ measurements to marine biologists whom can then advise policy makers on critical environmental issues. This poster presents recent field deployment activity of AUVs demonstrating the effectiveness of our embedded communication network infrastructure throughout southern California coastal waters. We also report on progress towards real-time, web-streaming data from the multiple sampling locations and mobile sensor platforms. Static monitoring sites included in this presentation detail the network nodes positioned at Redondo Beach and Marina Del Ray. One of the deployed mobile sensors highlighted here are autonomous Slocum gliders. These nodes operate in the open ocean for periods as long as one month. The gliders are connected to the network via a Freewave radio modem network composed of multiple coastal base-stations. This increases the efficiency of deployment missions by reducing operational expenses via reduced reliability on satellite phones for communication, as well as increasing the rate and amount of data that can be transferred. Another mobile sensor platform presented in this study are the autonomous robotic boats. These platforms are utilized for harbor and littoral zone studies, and are capable of performing multi-robot coordination while observing known communication constraints. All of these pieces fit together to present an overview of ongoing collaborative work to develop an autonomous, region-wide, coastal environmental observation and monitoring sensor network.

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We consider the problem of object tracking in a wireless multimedia sensor network (we mainly focus on the camera component in this work). The vast majority of current object tracking techniques, either centralised or distributed, assume unlimited energy, meaning these techniques don't translate well when applied within the constraints of low-power distributed systems. In this paper we develop and analyse a highly-scalable, distributed strategy to object tracking in wireless camera networks with limited resources. In the proposed system, cameras transmit descriptions of objects to a subset of neighbours, determined using a predictive forwarding strategy. The received descriptions are then matched at the next camera on the objects path using a probability maximisation process with locally generated descriptions. We show, via simulation, that our predictive forwarding and probabilistic matching strategy can significantly reduce the number of object-misses, ID-switches and ID-losses; it can also reduce the number of required transmissions over a simple broadcast scenario by up to 67%. We show that our system performs well under realistic assumptions about matching objects appearance using colour.

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This paper presents a method of recovering the 6 DoF pose (Cartesian position and angular rotation) of a range sensor mounted on a mobile platform. The method utilises point targets in a local scene and optimises over the error between their absolute position and their apparent position as observed by the range sensor. The analysis includes an investigation into the sensitivity and robustness of the method. Practical results were collected using a SICK LRS2100 mounted on a P&H electric mining shovel and present the errors in scan data relative to an independent 3D scan of the scene. A comparison to directly measuring the sensor pose is presented and shows the significant accuracy improvements in scene reconstruction using this pose estimation method.

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A Wireless Sensor Network (WSN) is a set of sensors that are integrated with a physical environment. These sensors are small in size, and capable of sensing physical phenomena and processing them. They communicate in a multihop manner, due to a short radio range, to form an Ad Hoc network capable of reporting network activities to a data collection sink. Recent advances in WSNs have led to several new promising applications, including habitat monitoring, military target tracking, natural disaster relief, and health monitoring. The current version of sensor node, such as MICA2, uses a 16 bit, 8 MHz Texas Instruments MSP430 micro-controller with only 10 KB RAM, 128 KB program space, 512 KB external ash memory to store measurement data, and is powered by two AA batteries. Due to these unique specifications and a lack of tamper-resistant hardware, devising security protocols for WSNs is complex. Previous studies show that data transmission consumes much more energy than computation. Data aggregation can greatly help to reduce this consumption by eliminating redundant data. However, aggregators are under the threat of various types of attacks. Among them, node compromise is usually considered as one of the most challenging for the security of WSNs. In a node compromise attack, an adversary physically tampers with a node in order to extract the cryptographic secrets. This attack can be very harmful depending on the security architecture of the network. For example, when an aggregator node is compromised, it is easy for the adversary to change the aggregation result and inject false data into the WSN. The contributions of this thesis to the area of secure data aggregation are manifold. We firstly define the security for data aggregation in WSNs. In contrast with existing secure data aggregation definitions, the proposed definition covers the unique characteristics that WSNs have. Secondly, we analyze the relationship between security services and adversarial models considered in existing secure data aggregation in order to provide a general framework of required security services. Thirdly, we analyze existing cryptographic-based and reputationbased secure data aggregation schemes. This analysis covers security services provided by these schemes and their robustness against attacks. Fourthly, we propose a robust reputationbased secure data aggregation scheme for WSNs. This scheme minimizes the use of heavy cryptographic mechanisms. The security advantages provided by this scheme are realized by integrating aggregation functionalities with: (i) a reputation system, (ii) an estimation theory, and (iii) a change detection mechanism. We have shown that this addition helps defend against most of the security attacks discussed in this thesis, including the On-Off attack. Finally, we propose a secure key management scheme in order to distribute essential pairwise and group keys among the sensor nodes. The design idea of the proposed scheme is the combination between Lamport's reverse hash chain as well as the usual hash chain to provide both past and future key secrecy. The proposal avoids the delivery of the whole value of a new group key for group key update; instead only the half of the value is transmitted from the network manager to the sensor nodes. This way, the compromise of a pairwise key alone does not lead to the compromise of the group key. The new pairwise key in our scheme is determined by Diffie-Hellman based key agreement.

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