933 resultados para ENDOCRINE DISRUPTION


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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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Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

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Ghrelin was first identified in 1999 by Kojima and colleagues (Kojima et al. 1999) as the natural ligand of an orphan G-protein coupled receptor, the Growth Hormone (GH) secretagogue receptor (GHS-R), which had been identified several years earlier through the actions of a growing number of synthetic growth hormone releasing peptides (GHRPs) and non-peptidyl GH secretagogues (Howard et al. 1996). Early studies, therefore, focussed on the actions of ghrelin as an important regulator of GH secretion. As a result Kojima et al (1999) designated this GH-releasing peptide, ghrelin (ghre is the Proto-Indo-European root of the word 'grow'). We now recognise that the functions of ghrelin extend well beyond its GH releasing actions and that it is a multi-functional peptide with both endocrine and autocrine/paracrine modes of action.

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The gonadotropin hypothesis proposes that elevated serum gonadotropin levels may increase the risk of epithelial ovarian cancer (EOC). We have studied the effect of treating EOC cell lines (OV207 and OVCAR-3) with FSH or LH. Both gonadotropins activated the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and increased cell migration that was inhibited by the MAPK 1 inhibitor PD98059. Both extra- and intracellular calcium ion signalling were implicated in gonadotropin-induced ERK1/2 activation as treatment with either the calcium chelator EGTA or an inhibitor of intracellular calcium release, dantrolene, inhibited gonadotropin-induced ERK1/2 activation. Verapamil was also inhibitory, indicating that gonadotropins activate calcium influx via L-type voltage-dependent calcium channels. The cAMP/protein kinase A (PKA) pathway was not involved in the mediation of gonadotropin action in these cells as gonadotropins did not increase intracellular cAMP formation and inhibition of PKA did not affect gonadotropin-induced phosphorylation of ERK1/2. Activation of ERK1/2 was inhibited by the protein kinase C (PKC) inhibitor GF 109203X as well as by the PKCδ inhibitor rottlerin, and downregulation of PKCδ was inhibited by small interfering RNA (siRNA), highlighting the importance of PKCδ in the gonadotropin signalling cascade. Furthermore, in addition to inhibition by PD98059, gonadotropin-induced ovarian cancer cell migration was also inhibited by verapamil, GF 109203X and rottlerin. Similarly, gonadotropin-induced proliferation was inhibited by PD98059, verapamil, GF 109203X and PKCδ siRNA. Taken together, these results demonstrate that gonadotropins induce both ovarian cancer cell migration and proliferation by activation of ERK1/2 signalling in a calcium- and PKCδ-dependent manner.

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Abstract Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.

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Perhaps the most innovative of all independent OLD ventures specialising in ROW content is Jaman. Founded in 2007 by IT entrepreneur Gaurav Dhillon, and based in San Mateo, California, Jaman is a quality specialist distributor of non-Hollywood films. As of late 2010, Jaman had 1.8 million registered users and attracts viewers from most countries in the world. 75% of all use is generated from outside the U.S. Jaman does very well in English speaking parts of the world, particularly current and former Commonwealth countries. The United Kingdom accounts for 29% of users, North America (U.S. and Canada) 26%, and India represents 23%. Jaman is sometimes referred to as ‘social cinema’: a website which brings together the critique and review of a cinephile website (the forums of Rue-morgue.com for cinefantastique movie fans for example) with the social interaction, community and functionality of a social media site (for example Facebook.com). Jaman could be considered a pioneer in this space; a first mover in wrapping commercial movie downloading in an interactive social experience.

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The main aim of this thesis is to analyse and optimise a public hospital Emergency Department. The Emergency Department (ED) is a complex system with limited resources and a high demand for these resources. Adding to the complexity is the stochastic nature of almost every element and characteristic in the ED. The interaction with other functional areas also complicates the system as these areas have a huge impact on the ED and the ED is powerless to change them. Therefore it is imperative that OR be applied to the ED to improve the performance within the constraints of the system. The main characteristics of the system to optimise included tardiness, adherence to waiting time targets, access block and length of stay. A validated and verified simulation model was built to model the real life system. This enabled detailed analysis of resources and flow without disruption to the actual ED. A wide range of different policies for the ED and a variety of resources were able to be investigated. Of particular interest was the number and type of beds in the ED and also the shift times of physicians. One point worth noting was that neither of these resources work in isolation and for optimisation of the system both resources need to be investigated in tandem. The ED was likened to a flow shop scheduling problem with the patients and beds being synonymous with the jobs and machines typically found in manufacturing problems. This enabled an analytic scheduling approach. Constructive heuristics were developed to reactively schedule the system in real time and these were able to improve the performance of the system. Metaheuristics that optimised the system were also developed and analysed. An innovative hybrid Simulated Annealing and Tabu Search algorithm was developed that out-performed both simulated annealing and tabu search algorithms by combining some of their features. The new algorithm achieves a more optimal solution and does so in a shorter time.

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Starting with the incident now known as the Cow’s Head Protest, this article traces and unpacks the events, techniques, and conditions surrounding the representation of ethno-religious minorities in Malaysia. The author suggests that the Malaysian Indians’ struggle to correct the dominant reading of their community as an impoverished and humbled underclass is a disruption of the dominant cultural order in Malaysia. It is also among the key events to have has set in motion a set of dynamics—the visual turn—introduced by new media into the politics of ethno-communal representation in Malaysia. Believing that this situation requires urgent examination the author attempts to outline the problematics of the task.

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This article explores the way in which a major Australian radiology organization implemented a complex accounting information system and how workers in the 72 radiology practises that had to use it resisted the change. The study reports on the issues that led to the circumvention of the system by individuals and, after only three years, complete withdrawal of the accounting information system by the parent organization. This article has implications for firms in the health care and other sectors considering implementing new accounting information systems. Organizations need to incorporate change management techniques and provide open communication to all stakeholders to minimize disruption and potential problems.

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Background: In vitro investigations have demonstrated the importance of the ribcage in stabilising the thoracic spine. Surgical alterations of the ribcage may change load-sharing patterns in the thoracic spine. Computer models are used in this study to explore the effect of surgical disruption of the rib-vertebrae connections on ligament load-sharing in the thoracic spine. Methods: A finite element model of a T7-8 motion segment, including the T8 rib, was developed using CT-derived spinal anatomy for the Visible Woman. Both the intact motion segment and the motion segment with four successive stages of destabilization (discectomy and removal of right costovertebral joint, right costotransverse joint and left costovertebral joint) were analysed for a 2000Nmm moment in flexion/extension, lateral bending and axial rotation. Joint rotational moments were compared with existing in vitro data and a detailed investigation of the load sharing between the posterior ligaments carried out. Findings: The simulated motion segment demonstrated acceptable agreement with in vitro data at all stages of destabilization. Under lateral bending and axial rotation, the costovertebral joints were of critical importance in resisting applied moments. In comparison to the intact joint, anterior destabilization increases the total moment contributed by the posterior ligaments. Interpretation: Surgical removal of the costovertebral joints may lead to excessive rotational motion in a spinal joint, increasing the risk of overload and damage to the remaining ligaments. The findings of this study are particularly relevant for surgical procedures involving rib head resection, such as some techniques for scoliosis deformity correction.

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In this video, the words animated on screen are sometimes the same and sometimes different from those spoken by a male voice. Both narratives, written and spoken, are constructed entirely from clichés and mixed metaphors. This work examines processes of signification. It emphasizes disruption and disconnection as fundamental and generative operations in making meaning. Extending on post-structural and deconstructionist ideas, this work questions the relationship between written and spoken words. It upsets the assumed efficacy of metaphors and clichés to question the sites and mechanisms of signification.

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In this video, a couple sits on a couch slowly breaking up. A typical shot/reverse-shot filmic structure is offset as the sound and image goes out of synch. At different times, it becomes so out of synch that they mouth each other’s words. This work engages with the signifying processes of romantic narratives. It emphasizes disruption and discontinuity as fundamental and generative operations in making meaning. Extending on post-structural and deconstructionist ideas, this work emphasizes the constructed nature of representations of heterosexual relationships. It draws attention to the gaps, slippages and fragments that pervade signifying acts.