Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis.

During epithelial ovarian cancer (EOC) progression, intraperitoneally disseminating tumor cells and multicellular aggregates (MCAs) present in ascites fluid adhere to the peritoneum and induce retraction of the peritoneal mesothelial monolayer prior to invasion of the collagen-rich submesothelial matrix and proliferation into macro-metastases. Clinical studies have shown heterogeneity among EOC metastatic units with respect to cadherin expression profiles and invasive behavior; however, the impact of distinct cadherin profiles on peritoneal anchoring of metastatic lesions remains poorly understood. In the current study, we demonstrate that metastasis-associated behaviors of ovarian cancer cells and MCAs are influenced by cellular cadherin composition. Our results show that mesenchymal N-cadherin-expressing (Ncad+) cells and MCAs invade much more efficiently than E-cadherin-expressing (Ecad+) cells. Ncad+ MCAs exhibit rapid lateral dispersal prior to penetration of three-dimensional collagen matrices. When seeded as individual cells, lateral migration and cell-cell junction formation precede matrix invasion. Neutralizing the Ncad extracellular domain with the monoclonal antibody GC-4 suppresses lateral dispersal and cell penetration of collagen gels. In contrast, use of a broad-spectrum matrix metalloproteinase (MMP) inhibitor (GM6001) to block endogenous membrane type 1 matrix metalloproteinase (MT1-MMP) activity does not fully inhibit cell invasion. Using intact tissue explants, Ncad+ MCAs were also shown to efficiently rupture peritoneal mesothelial cells, exposing the submesothelial collagen matrix. Acquisition of Ncad by Ecad+ cells increased mesothelial clearance activity but was not sufficient to induce matrix invasion. Furthermore, co-culture of Ncad+ with Ecad+ cells did not promote a 'leader-follower' mode of collective cell invasion, demonstrating that matrix remodeling and creation of invasive micro-tracks are not sufficient for cell penetration of collagen matrices in the absence of Ncad. Collectively, our data emphasize the role of Ncad in intraperitoneal seeding of EOC and provide the rationale for future studies targeting Ncad in preclinical models of EOC metastasis

Conserving pattern and process in the Southern Ocean: designing a Marine Protected Area for the Prince Edward Islands

South Africa is currently proclaiming a Marine Protected Area (MPA) in the Exclusive Economic Zone (EEZ) of its sub-Antarctic Prince Edward Islands. The objectives of the MPA are to: 1) contribute to a national and global representative system of MPAs, 2) serve as a scientific reference point to inform future management, 3) contribute to the recovery of the Patagonian toothfish (Dissostichus eleginoides), and 4) reduce the bird bycatch of the toothfish fishery, particularly of albatrosses and petrels. This study employs systematic conservation planning methods to delineate a MPA within the EEZ that will conserve biodiversity patterns and processes within sensible management boundaries, while minimizing conflict with the legal toothfish fishery. After collating all available distributional data on species, benthic habitats and ecosystem processes, we used C-Plan software to delineate a MPA with three management zones: four IUCN Category Ia reserves (13% of EEZ); two Conservation Zones (21% of EEZ); and three Category IV reserves (remainder of EEZ). Compromises between conservation target achievement and the area required by the MPA are apparent in the final reserve design. The proposed MPA boundaries are expected to change over time as new data become available and as impacts of climate change become more evident

Profile of cytokines, growth factors and chemokines during attacks of FMF

PubMe

Designing multiplayer games to facilitate emergent social behaviours online

This paper discusses an exploratory case study of the design of games that facilitate spontaneous social interaction and group behaviours among distributed individuals, based largely on symbolic presence 'state' changes. We present the principles guiding the design of our game environment: presence as a symbolic phenomenon, the importance of good visualization and the potential for spontaneous self-organization among groups of people. Our game environment, comprising a family of multiplayer 'bumper-car' style games, is described, followed by a discussion of lessons learned from observing users of the environment. Finally, we reconsider and extend our design principles in light of our observations

Analysis of parallel process in HVAC systems using deep autoencoders

P. 15-26Heating, Ventilation, and Air Conditioning (HVAC) systems are generally built in a modular manner, comprising several identical subsystems in order to achieve their nominal capacity. These parallel subsystems and elements should have the same behavior and, therefore, differences between them can reveal failures and inefficiency in the system. The complexity in HVAC systems comes from the number of variables involved in these processes. For that reason, dimensionality reduction techniques can be a useful approach to reduce the complexity of the HVAC data and study their operation. However, for most of these techniques, it is not possible to project new data without retraining the projection and, as a result, it is not possible to easily compare several projections. In this paper, a method based on deep autoencoders is used to create a reference model with a HVAC system and new data is projected using this model to be able to compare them. The proposed approach is applied to real data from a chiller with 3 identical compressors at the Hospital of LeónS

Characterizations and first plasma operation of the WEST load-resilient actively cooled ICRF launchers

The paper discusses the characterization of the three high power steady-state and load-resilient ICRF launchers of WEST before their installation in the tokamak. These launchers have been characterized and validated in low-power experiments (milliwatt range) as well as in experiments at the nominal RF voltages and currents in the TITAN vacuum chamber (~30 kV and 915 A peak). The successful commissioning of two of the launchers during the WEST C3 campaign at ~1 MW power level is illustrated. Manual and real-time controlled impedance-matching of the launchers are discussed, as well as the validation of their load-resilience. Furthermore, several redundant and complementary protection systems have been validated and are reviewed in the paper

Fog paradigm for local energy management systems

Cloud Computing infrastructures have been extensively deployed to support energy computation within built environments. This has ranged from predicting potential energy demand for a building (or a group of buildings), undertaking heat profile/energy distribution simulations, to understanding the impact of climate and weather on building operation. Cloud computing usage in these scenarios have benefited from resource elasticity, where the number and types of resources can change based on the complexity of the simulation being considered. While there are numerous advantages of using a cloud based energy management system, there are also significant limitations. For instance, many such systems assume that the data has been pre-staged at a cloud platform prior to simulation, and do not take account of data transfer times from the building to the simulation platform. The need for supporting computation at edge resources, which can be hosted within the building itself or shared within a building complex, has become important over recent year. Additionally, network connectivity between the sensing infrastructure within a built environment and a data centre where analysis is to be carried out can be intermittent or may fail. There is therefore also a need to better understand how computation/analysis can be carried out closer to the data capture site to complement analysis that would be undertaken at the data centre. We describe how the Fog computing paradigm can be used to support some of these requirements, extending the capability of a data centre to support energy simulation within built environments

Mouse podoplanin supports adhesion and aggregation of platelets under arterial shear: a novel mechanism of haemostasis

The Podoplanin-CLEC-2 axis is critical in mice for prevention of haemorrhage in the cerebral vasculature during mid-gestation. This raises the question as to how platelets are captured by podoplanin on neuroepithelial cells in a high shear environment. In this study, we demonstrate that mouse platelets form stable aggregates on mouse podoplanin at arterial shear through a CLEC-2 and Src kinase-dependent pathway. Adhesion and aggregation are also dependent on the platelet glycoprotein (GP) receptors, integrin αIIbβ3 and GPIb, and the feedback agonists ADP and thromboxane A2 (TxA2). CLEC-2 does not bind to von Willebrand factor (VWF) suggesting that the interaction with podoplanin is sufficient to both tether and activate platelets. Consistent with this, surface plasmon resonance measurements reveal that mouse CLEC-2 binds to mouse podoplanin with nanomolar affinity. The present findings demonstrate a novel pathway of haemostasis in which podoplanin supporting platelet capture and activation at arteriolar rates of shear

Habitation

Dans un contexte concurrentiel accru, les industries doivent développer de nouvelles solutions pour répondre à des défis majeurs (innovation, design, fonctionnalité, consommation…). La plastronique, qui est au confluent des domaines de la plasturgie et de l’électronique, permet de répondre à ces nouvelles attentes, en proposant des objets intelligents et connectés. Elle offre la possibilité de concevoir des systèmes de forme complexe 3D. Dans ce contexte de rupture technologique, l’innovation est à l’interface du génie électrique, de la mécatronique et de la plasturgie. Elle fait également appel à des domaines connexes et indispensables tels que la physique et la chimie. La convergence de ces domaines rend indispensable l’acquisition de nouvelles connaissances et compétences transverses dans les métiers de demain. Pour répondre à ces besoins, une formation en plastronique est en émergence à l’Université de Lyon. Les modalités seront décrites dans cet article. Les compétences initiales des apprenants seront élargies pour acquérir les bases théoriques et pratiques de la conception de systèmes plastroniques. Cette formation s’appuiera sur des projets concrets en lien direct avec les acteurs variés de la filière (aéronautique, médical, robotique, etc.). Le prototypage y tiendra une place importante, en permettant de confronter les apprenants à des problématiques industrielles concrètes

Effect of a low-intensity, self-management lifestyle intervention on knee pain in community-based young to middle-aged rural women: a cluster randomised controlled trial

BACKGROUND:Knee pain is common with obesity and weight gain being important risk factors. Previous clinical trials have focused on overweight or obese adults with knee pain and osteoarthritis and demonstrated modest effects of intense weight loss programs on reducing knee pain despite very significant weight loss. There has been no lifestyle intervention that targets community-based adults to test its effect on prevention of knee pain. We aimed to determine the effect of a simple low-intensity self-management lifestyle intervention (HeLP-her), proven in randomised controlled trials to improve lifestyle and prevent weight gain, on knee pain in community-based young to middle-aged rural women. METHODS:A 1-year pragmatic, cluster randomised controlled trial was conducted in 649 community-based women (aged 18-50 years) to receive either the HeLP-her program (consisting of one group session, monthly SMS text messages, one phone coaching session, and a program manual) or one general women's health education session. Secondary analyses were performed in 390 women who had knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and 12-month follow-up. "Any knee pain" was defined as a WOMAC pain score ≥ 1. Knee pain worsening was defined as an increase in WOMAC pain score over 12 months. RESULTS:Thirty-five percent of women had "any knee pain" at baseline. The risk of knee pain worsening did not differ between the intervention and control groups over 12 months. For women with any knee pain at baseline, those in the intervention arm had a lower risk of knee pain worsening compared with those in the control arm (OR 0.37, 95% CI 0.14-1.01, p = 0.05), with a stronger effect observed in women with body mass index ≥ 25 kg/m2 (OR 0.28, 95% CI 0.09-0.87, p = 0.03). CONCLUSIONS:In community-based young to middle-aged women, a simple low-intensity lifestyle program reduced the risk of knee pain worsening in those with any knee pain at baseline, particularly in those overweight or obese. Pragmatic lifestyle programs such as HeLP-her may represent a feasible lifestyle intervention to reduce the burden of knee pain in the community. TRIAL REGISTRATION:ACTRN12612000115831 , registered 24 January 2012.Yuanyuan Wang, Catherine Lombard, Sultana Monira Hussain, Cheryce Harrison, Samantha Kozica, Sharmayne R. E. Brady, Helena Teede and Flavia M. Cicuttin