Perfluorocarbon Particle Size Influences Magnetic Resonance Signal and Immunological Properties of Dendritic Cells

The development of cellular tracking by fluorine (19F) magnetic resonance imaging (MRI) has introduced a number of advantages for following immune cell therapies in vivo. These include improved signal selectivity and a possibility to correlate cells labeled with fluorine-rich particles with conventional anatomic proton (1H) imaging. While the optimization of the cellular labeling method is clearly important, the impact of labeling on cellular dynamics should be kept in mind. We show by 19F MR spectroscopy (MRS) that the efficiency in labeling cells of the murine immune system (dendritic cells) by perfluoro-15-crown-5-ether (PFCE) particles increases with increasing particle size (560>365>245>130 nm). Dendritic cells (DC) are professional antigen presenting cells and with respect to impact of PFCE particles on DC function, we observed that markers of maturation for these cells (CD80, CD86) were also significantly elevated following labeling with larger PFCE particles (560 nm). When labeled with these larger particles that also gave an optimal signal in MRS, DC presented whole antigen more robustly to CD8+ T cells than control cells. Our data suggest that increasing particle size is one important feature for optimizing cell labeling by PFCE particles, but may also present possible pitfalls such as alteration of the immunological status of these cells. Therefore depending on the clinical scenario in which the 19F-labeled cellular vaccines will be applied (cancer, autoimmune disease, transplantation), it will be interesting to monitor the fate of these cells in vivo in the relevant preclinical mouse models

First year of energetic particle measurements in the inner heliosphere with Solar Orbiter's Energetic Particle Detector

Context. Solar Orbiter strives to unveil how the Sun controls and shapes the heliosphere and fills it with energetic particle radiation. To this end, its Energetic Particle Detector (EPD) has now been in operation, providing excellent data, for just over a year. Aims. EPD measures suprathermal and energetic particles in the energy range from a few keV up to (near-) relativistic energies (few MeV for electrons and about 500 MeV nuc−1 for ions). We present an overview of the initial results from the first year of operations and we provide a first assessment of issues and limitations. In addition, we present areas where EPD excels and provides opportunities for significant scientific progress in understanding how our Sun shapes the heliosphere. Methods. We used the solar particle events observed by Solar Orbiter on 21 July and between 10 and 11 December 2020 to discuss the capabilities, along with updates and open issues related to EPD on Solar Orbiter. We also give some words of caution and caveats related to the use of EPD-derived data. Results. During this first year of operations of the Solar Orbiter mission, EPD has recorded several particle events at distances between 0.5 and 1 au from the Sun. We present dynamic and time-averaged energy spectra for ions that were measured with a combination of all four EPD sensors, namely: the SupraThermal Electron and Proton sensor (STEP), the Electron Proton Telescope (EPT), the Suprathermal Ion Spectrograph (SIS), and the High-Energy Telescope (HET) as well as the associated energy spectra for electrons measured with STEP and EPT. We illustrate the capabilities of the EPD suite using the 10 and 11 December 2020 solar particle event. This event showed an enrichment of heavy ions as well as 3He, for which we also present dynamic spectra measured with SIS. The high anisotropy of electrons at the onset of the event and its temporal evolution is also shown using data from these sensors. We discuss the ongoing in-flight calibration and a few open instrumental issues using data from the 21 July and the 10 and 11 December 2020 events and give guidelines and examples for the usage of the EPD data. We explain how spacecraft operations may affect EPD data and we present a list of such time periods in the appendix. A list of the most significant particle enhancements as observed by EPT during this first year is also provided.Ministerio de Economía y CompetitividadAgencia Estatal de Investigació

The Solar Orbiter Science Activity Plan: translating solar and heliospheric physics questions into action

Solar Orbiter is the first space mission observing the solar plasma both in situ and remotely, from a close distance, in and out of the ecliptic. The ultimate goal is to understand how the Sun produces and controls the heliosphere, filling the Solar System and driving the planetary environments. With six remote-sensing and four in-situ instrument suites, the coordination and planning of the operations are essential to address the following four top-level science questions: (1) What drives the solar wind and where does the coronal magnetic field originate?; (2) How do solar transients drive heliospheric variability?; (3) How do solar eruptions produce energetic particle radiation that fills the heliosphere?; (4) How does the solar dynamo work and drive connections between the Sun and the heliosphere? Maximising the mission’s science return requires considering the characteristics of each orbit, including the relative position of the spacecraft to Earth (affecting downlink rates), trajectory events (such as gravitational assist manoeuvres), and the phase of the solar activity cycle. Furthermore, since each orbit’s science telemetry will be downloaded over the course of the following orbit, science operations must be planned at mission level, rather than at the level of individual orbits. It is important to explore the way in which those science questions are translated into an actual plan of observations that fits into the mission, thus ensuring that no opportunities are missed. First, the overarching goals are broken down into specific, answerable questions along with the required observations and the so-called Science Activity Plan (SAP) is developed to achieve this. The SAP groups objectives that require similar observations into Solar Orbiter Observing Plans, resulting in a strategic, top-level view of the optimal opportunities for science observations during the mission lifetime. This allows for all four mission goals to be addressed. In this paper, we introduce Solar Orbiter’s SAP through a series of examples and the strategy being followed

Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

The first widespread solar energetic particle event observed by Solar Orbiter on 2020 November 29

Context. On 2020 November 29, the first widespread solar energetic particle (SEP) event of solar cycle 25 was observed at four widely separated locations in the inner (. 1 AU) heliosphere. Relativistic electrons as well as protons with energies > 50 MeV were observed by Solar Orbiter (SolO), Parker Solar Probe (PSP), the Solar Terrestrial Relations Observatory (STEREO)-A and multiple near-Earth spacecraft. The SEP event was associated with an M4.4 class X-ray flare and accompanied by a coronal mass ejection (CME) and an extreme ultraviolet (EUV) wave as well as a type II radio burst and multiple type III radio bursts. Aims. We present multi-spacecraft particle observations and place them in context with source observations from remote sensing instruments and discuss how such observations may further our understanding of particle acceleration and transport in this widespread event. Methods. Velocity dispersion analysis (VDA) and time shift analysis (TSA) were used to infer the particle release times at the Sun. Solar wind plasma and magnetic field measurements were examined to identify structures that influence the properties of the energetic particles such as their intensity. Pitch angle distributions and first-order anisotropies were analyzed in order to characterize the particle propagation in the interplanetary medium. Results. We find that during the 2020 November 29 SEP event, particles spread over more than 230° in longitude close to 1 AU. The particle onset delays observed at the different spacecraft are larger as the flare–footpoint angle increases and are consistent with those from previous STEREO observations. Comparing the timing when the EUV wave intersects the estimated magnetic footpoints of each spacecraft with particle release times from TSA and VDA, we conclude that a simple scenario where the particle release is only determined by the EUV wave propagation is unlikely for this event. Observations of anisotropic particle distributions at SolO, Wind, and STEREO-A do not rule out that particles are injected over a wide longitudinal range close to the Sun. However, the low values of the first-order anisotropy observed by near-Earth spacecraft suggest that diffusive propagation processes are likely involve

The first widespread solar energetic particle event observed by Solar Orbiter on 2020 November 29

Context. On 2020 November 29, the first widespread solar energetic particle (SEP) event of solar cycle 25 was observed at four widely separated locations in the inner (less than or similar to 1AU) heliosphere. Relativistic electrons as well as protons with energies >50MeV were observed by Solar Orbiter (SolO), Parker Solar Probe, the Solar Terrestrial Relations Observatory (STEREO)-A and multiple near-Earth spacecraft. The SEP event was associated with an M4.4 class X-ray flare and accompanied by a coronal mass ejection and an extreme ultraviolet (EUV) wave as well as a type II radio burst and multiple type III radio bursts.Aims. We present multi-spacecraft particle observations and place them in context with source observations from remote sensing instruments and discuss how such observations may further our understanding of particle acceleration and transport in this widespread event.Methods. Velocity dispersion analysis (VDA) and time shift analysis (TSA) were used to infer the particle release times at the Sun. Solar wind plasma and magnetic field measurements were examined to identify structures that influence the properties of the energetic particles such as their intensity. Pitch angle distributions and first-order anisotropies were analyzed in order to characterize the particle propagation in the interplanetary medium.Results. We find that during the 2020 November 29 SEP event, particles spread over more than 230 degrees in longitude close to 1AU. The particle onset delays observed at the different spacecraft are larger as the flare-footpoint angle increases and are consistent with those from previous STEREO observations. Comparing the timing when the EUV wave intersects the estimated magnetic footpoints of each spacecraft with particle release times from TSA and VDA, we conclude that a simple scenario where the particle release is only determined by the EUV wave propagation is unlikely for this event. Observations of anisotropic particle distributions at SolO, Wind, and STEREO-A do not rule out that particles are injected over a wide longitudinal range close to the Sun. However, the low values of the first-order anisotropy observed by near-Earth spacecraft suggest that di ffusive propagation processes are likely involved.</p

First near-relativistic solar electron events observed by EPD onboard Solar Orbiter

Context. Solar Orbiter, launched in February 2020, started its cruise phase in June 2020, in coincidence with its first perihelion at 0.51 au from the Sun. The in situ instruments onboard, including the Energetic Particle Detector (EPD), operate continuously during the cruise phase enabling the observation of solar energetic particles. Aims. In situ measurements of the first near-relativistic solar electron events observed in July 2020 by EPD are analyzed and the solar origins and the conditions for the interplanetary transport of these particles investigated. Methods. Electron observations from keV energies to the near-relativistic range were combined with the detection of type III radio bursts and extreme ultraviolet (EUV) observations from multiple spacecraft in order to identify the solar origin of the electron events. Electron anisotropies and timing as well as the plasma and magnetic field environment were evaluated to characterize the interplanetary transport conditions. Results. All electron events were clearly associated with type III radio bursts. EUV jets were also found in association with all of them except one. A diversity of time profiles and pitch-angle distributions was observed. Different source locations and different magnetic connectivity and transport conditions were likely involved. The July 11 event was also detected by Wind, separated 107 degrees in longitude from Solar Orbiter. For the July 22 event, the Suprathermal Electron and Proton sensor of EPD allowed for us to not only resolve multiple electron injections at low energies, but it also provided an exceptionally high pitch-angle resolution of a very anisotropic beam. This, together with radio observations of local Langmuir waves suggest a very good magnetic connection during the July 22 event. This scenario is challenged by a high-frequency occultation of the type III radio burst and a nominally non-direct connection to the source; therefore, magnetic connectivity requires further investigation.</p

In-flight verification of the engineering design data for the Energetic Particle Detector on board the ESA/NASA Solar Orbiter

This work presents an overview of the in-flight engineering data of the Energetic Particle Detector (EPD) instrument suite during its first year of operation. EPD is part of the in-situ scientific payload of the ESA/NASA Solar Orbiter mission which was launched in February 2020. After completion of its commissioning phase, Solar Orbiter started its cruise phase in June 2020, in coincidence with its first perihelion at 0.51 au. Six remote-sensing instruments and four in-situ instruments, including EPD, which is a suite of four individual sensors, make Solar Orbiter the most complete space laboratory flown into the inner heliosphere to date. In-flight engineering data of the different EPD units such as their power consumption and their temperatures are the key indicators to ascertain that the design, manufacturing and qualification of the EPD units on ground and throughout the different life cycles prior to launch were successful. On the other hand, these in-flight housekeeping data also reflect the general status of the units which are exposed to space radiation, stray light and a varying thermal environment. The reliability of the EPD suite was analyzed during the design phase and the in-flight status evaluation confirms this analysis. The first year of flight covers special milestones for the Solar Orbiter mission such as the launch, first perihelion, as well as the first Venus flyby. By evaluating the in-flight engineering data, it is demonstrated that the EPD suite successfully meets its design requirements and also satisfies its scientific objectives in flight