22 research outputs found

    Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection

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    Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained regions of the virus in order to ensure the maintenance of immunodominant CD8 responses and the sustained decline of early viremia

    Cold atoms in space: community workshop summary and proposed road-map

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    We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

    Recent Joint Studies Related to the Development of Space Radioisotope Power Systems

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    Over the last several years there has been a mutually beneficial ongoing technical interchange between the U.K and the U.S. related to various aspects of space radioisotope power systems (RPS). While this interchange has been primarily focused on materials based activities, it has also included some aspects related to safety, environmental, and lessons learned during the application of RPSs by the U.S. during the last fifty years. Recent joint technical RPS endeavors have centered on the development of a possible “cold” ceramic surrogate for 238PuO2 and 241AmOx and the irradiation of thermoelectrics and other materials at expected RPS related neutron fluences. As the U.S. continues to deploy and Europe develops RPS capability, on-going joint RPS technical interfaces will continue to enhance each entities’ endeavors in this nuclear based power technology critical for deep space exploration

    European Radioisotope Thermoelectric Generators (RTGs) and Radioisotope Heater Units (RHUs) for Space Science and Exploration

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    Radioisotope power systems utilising americium-241 as a source of heat have been under development in Europe as part of a European Space Agency funded programme since 2009. The aim is to develop all of the building blocks that would enable Europe to launch and operate deep space and planetary missions in environments where use of solar power or alternative power generation technologies is challenging. Although some technical and policy work activity predate the ESA programme, the maturity of the technology has now reached a level that it can be incorporated in mission studies and roadmaps targeting the period from the mid 2020s onwards. This paper describes the state of the art in European radioisotope thermoelectric generators and radioisotope heater units. This paper includes: the evolution of the technical programme in detail; descriptions of the design; evolution of RTG and RHU devices from laboratory prototypes to more advanced fully functional systems; and experimental data obtained to date. This paper also outlines the technical challenges and multidisciplinary skills required to develop what is a world leading, original, significant and transformative technology solution for planetary science and exploration missions from the mid 2020s onwards.JRC.G.I.3-Nuclear Fuel Safet
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