Antigen quality determines the efficiency of antitumor immune responses generated in the absence of regulatory T cells

The observation that depletion or inhibition of regulatory T cells (Tregs) unleashes efficient antitumor effector immune responses that can lead to tumor eradication in mice has opened new perspectives for the development of cancer immunotherapy. The quality and overall efficiency of the effector immune responses induced in the absence of Tregs seem to depend on multiple factors that determine the result of a battle involving effector T cells (Teffs), Tregs and tumor cells. In this study, we investigated the quality of tumor-associated antigens (TAAs) as one such factor. We show that the presence of a strong dominant antigen is required for the induction of effector responses capable of tumor eradication in the absence of Tregs. The sole addition of a dominant antigen on tumor cells does not change tumor growth in unmanipulated mice, but improves tumor eradication rate from a few to almost 100% in the absence of Tregs. This eradication can be shown to result from the recruitment and activation of specific Teffs recognizing this antigen. We also show that the presence of such dominant antigens has the side effect of restricting the breadth of the immune response to other TAAs, which could favor the generation of escape mutant by tumor editing. Taken together, our results highlight the potential, and some requirements for cancer immunotherapy based on Treg depletion. They also show that, ultimately, tumor fate depends on multiple factors that should all be taken into consideration for the design of more efficient immunotherapy

Multimedia delivery in the future internet

The term “Networked Media” implies that all kinds of media including text, image, 3D graphics, audio and video are produced, distributed, shared, managed and consumed on-line through various networks, like the Internet, Fiber, WiFi, WiMAX, GPRS, 3G and so on, in a convergent manner [1]. This white paper is the contribution of the Media Delivery Platform (MDP) cluster and aims to cover the Networked challenges of the Networked Media in the transition to the Future of the Internet. Internet has evolved and changed the way we work and live. End users of the Internet have been confronted with a bewildering range of media, services and applications and of technological innovations concerning media formats, wireless networks, terminal types and capabilities. And there is little evidence that the pace of this innovation is slowing. Today, over one billion of users access the Internet on regular basis, more than 100 million users have downloaded at least one (multi)media file and over 47 millions of them do so regularly, searching in more than 160 Exabytes1 of content. In the near future these numbers are expected to exponentially rise. It is expected that the Internet content will be increased by at least a factor of 6, rising to more than 990 Exabytes before 2012, fuelled mainly by the users themselves. Moreover, it is envisaged that in a near- to mid-term future, the Internet will provide the means to share and distribute (new) multimedia content and services with superior quality and striking flexibility, in a trusted and personalized way, improving citizens’ quality of life, working conditions, edutainment and safety. In this evolving environment, new transport protocols, new multimedia encoding schemes, cross-layer inthe network adaptation, machine-to-machine communication (including RFIDs), rich 3D content as well as community networks and the use of peer-to-peer (P2P) overlays are expected to generate new models of interaction and cooperation, and be able to support enhanced perceived quality-of-experience (PQoE) and innovative applications “on the move”, like virtual collaboration environments, personalised services/ media, virtual sport groups, on-line gaming, edutainment. In this context, the interaction with content combined with interactive/multimedia search capabilities across distributed repositories, opportunistic P2P networks and the dynamic adaptation to the characteristics of diverse mobile terminals are expected to contribute towards such a vision. Based on work that has taken place in a number of EC co-funded projects, in Framework Program 6 (FP6) and Framework Program 7 (FP7), a group of experts and technology visionaries have voluntarily contributed in this white paper aiming to describe the status, the state-of-the art, the challenges and the way ahead in the area of Content Aware media delivery platforms

A Modular Design for the 56 Variants of the Short Straight Section in the Arcs of the Large Hadron Collider (LHC)

The 360 Short Straight Sections (SSS) necessary for the eight arcs of the LHC machine have to fulfil different requirements. Their main function is to house the lattice two-in-one superconducting quadrupole and various correction magnets, all operating at 1.9 K in a superfluid helium bath. The magnetic and powering schemes of the arcs and the fact that the two proton beams alternate between the inner and outer magnet channels impose 24 different combinations of magnet assemblies, all housed in an identical helium enclosure. The cryogenic architecture of the LHC machine is based on cryogenic loops spanning over one half-cell (53 m) for the 4.6-20 K circuit, over a full cell (107 m) for the 1.9 K circuits, up to the full arc (about 2.3 km) for the shield cooling line. This cryogenic layout, when superimposed to the magnetic scheme, further complicated by the cryostat insulation vacuum sectorisation every 2 cells, creates additional assembly variants, up to a total number of 56. The required flexibility in the manufacture and assembly, as well as economic considerations, have led to a modular design for the different SSS components and sub-assemblies. This modularity allows to "specialise" the SSS at the latest possible assembly step of the "just in time" production line. This paper presents the conceptual design considerations to achieve this modularity, the SSS design retained for the series manufacture, and the assembly procedures recently validated on a prototype program at CERN

Impacts of climate change on plant diseases – opinions and trends

There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods

Admission of advanced lung cancer patients to intensive care unit: A retrospective study of 76 patients

<p>Abstract</p> <p>Background</p> <p>Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications.</p> <p>Methods</p> <p>We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006.</p> <p>Results</p> <p>Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay.</p> <p>Conclusions</p> <p>Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.</p

Evolution of the Population Structure of Staphylococcus pseudintermedius in France

Staphylococcus pseudintermedius is a colonizer as well as an important pathogen of dogs where it is responsible for skin, ear and post-operative infections. The emergence of methicillin-resistant S. pseudintermedius (MRSP) in the early 2000s, which were additionally resistant to most veterinary-licensed antibiotics, drew specific attention to these pathogens due to the limitations created in veterinary therapeutic options. Multiple studies showed that the sequence type (ST)71 was the most frequently identified clone in Europe. A few years ago, several publications have suggested a decline of the ST71 clone and the emergence of the ST258 lineage in Northern Europe. In this study, we show that ST71 is also decreasing over time in France and that the non-ST71 population is highly heterogeneous. Globally, the non-ST71 clones are more susceptible to antibiotics, which might be good news for veterinarians. Two other lineages, ST258 and ST496, seem to be successful in France. These isolates, as well as representatives of the ST71 clone, underwent whole-genome sequence. This study shows that the ST71 and ST496 clusters are highly homogenous while the ST258 cluster is more diverse. Each ST possesses a specific pattern of resistance and virulence genes. The reasons for the apparent and simultaneous success of the ST258 and ST496 clones remain unclear. But the emergence of the ST496 clone will require monitoring given its multi-resistant genotype and threat to canine health

Cork oak vulnerability to fire: the role of bark harvesting, tree characteristics and abiotic factors

Forest ecosystems where periodical tree bark harvesting is a major economic activity may be particularly vulnerable to disturbances such as fire, since debarking usually reduces tree vigour and protection against external agents. In this paper we asked how cork oak Quercus suber trees respond after wildfires and, in particular, how bark harvesting affects post-fire tree survival and resprouting. We gathered data from 22 wildfires (4585 trees) that occurred in three southern European countries (Portugal, Spain and France), covering a wide range of conditions characteristic of Q. suber ecosystems. Post-fire tree responses (tree mortality, stem mortality and crown resprouting) were examined in relation to management and ecological factors using generalized linear mixed-effects models. Results showed that bark thickness and bark harvesting are major factors affecting resistance of Q. suber to fire. Fire vulnerability was higher for trees with thin bark (young or recently debarked individuals) and decreased with increasing bark thickness until cork was 3–4 cm thick. This bark thickness corresponds to the moment when exploited trees are debarked again, meaning that exploited trees are vulnerable to fire during a longer period. Exploited trees were also more likely to be top-killed than unexploited trees, even for the same bark thickness. Additionally, vulnerability to fire increased with burn severity and with tree diameter, and was higher in trees burned in early summer or located in drier south-facing aspects. We provided tree response models useful to help estimating the impact of fire and to support management decisions. The results suggested that an appropriate management of surface fuels and changes in the bark harvesting regime (e.g. debarking coexisting trees in different years or increasing the harvesting cycle) would decrease vulnerability to fire and contribute to the conservation of cork oak ecosystemsinfo:eu-repo/semantics/publishedVersio